Estrogen receptor α (ERα) is a ligand‐dependent transcription factor that regulates the expression of estrogen‐responsive genes. Approximately 70% of patients with breast cancer are ERα positive. Estrogen stimulates cancer cell proliferation and contributes to tumor progression. Endocrine therapies, which suppress the ERα signaling pathway, significantly improve the prognosis of patients with breast cancer. However, the development of de novo or acquired endocrine therapy resistance remains a barrier to breast cancer treatment. Therefore, understanding the regulatory mechanisms of ERα (...) is essential to overcome the resistance to treatment. This review focuses on the regulation of ERα expression, including copy number variation, epigenetic regulation, transcriptional regulation, and stability, as well as functions from the point of view post‐translational modifications. (shrink)

Although estrogens are widely considered circulating “sex steroid hormones” typically associated with female reproduction, recent evidence suggests that estrogens can act as local modulators of brain circuits in both males and females. The functional implications of this newly characterized estrogen signaling system have begun to emerge. This essay summarizes evidence in support of the hypothesis that the rapid production of estrogens in brain circuits can drive acute changes in both the production and perception of acoustic communication behaviors. These studies (...) have revealed two fundamental neurobiological concepts: (1) estrogens can be locally produced in brain circuits, independent of levels in nearby circuits and in the circulation and (2) estrogens can have very rapid effects within these brain circuits to modulate social vocalizations, acoustic processing, and sensorimotor integration. This vertebrate‐wide span of research, including vocalizing fishes, amphibians, and birds, emphasizes the importance of comparative model systems in understanding principles of neurobiology. (shrink)

The classical estrogen receptor model does not sufficiently account for the tumor‐promoting activity of extrogens or for the antiproliferative effect of antiestrogens in estrogen‐dependent tumors. Particular difficulties not readily accommodated within the model are that hormonal autonomy can supervene without loss of the estrogen receptor and that antiestrogen effects are highly context‐dependent, without apparent differences in the estrogen receptor itself or in metabolic transformation of antiestrogens. Recent studies suggest that estrogens may promote cell proliferation, in part, (...) through the mediation of growth factors and that antiestrogens may exert some of their effects by mechanisms unrelated to the estrogen receptor. (shrink)

There is some very limited evidence for a role of estrogens in human psychosexual masculinization; its interpretation is uncertain. Fitch & Denenberg's demonstration of a role for estrogens in the behavioral feminization of nonhuman mammals implicitly suggests an answer to a riddle posed by the syndrome of congenital adrenal hyperplasia in women.

The relation between sex hormones and responses to partner infidelity was explored in two studies reported here. The first confirmed the standard sex difference in relationship jealousy, that males (n=133) are relatively more distressed by a partner’s sexual infidelity and females (n=159) by a partner’s emotional infidelity. The study also revealed that females using hormone-based birth control (n=61) tended more toward sexual jealousy than did other females, and reported more intense affective responses to partner infidelity (n=77). In study two, 47 (...) females were assessed four times across one month. Patterns of response to partner infidelity did not vary by week of menstrual cycle, but significant relations between salivary estradiol level and jealousy responses were obtained during the time of rising and high fertility risk. The implications, at least for females, are that any evolved psychological, affective, or behavioral dispositions regarding reproduction-related relationships are potentially moderated by estradiol, and that the use of synthetic hormones may disrupt this relation. (shrink)

The Estrogen Elixir: A History of Hormone Replacement Therapy in America by Elizabeth Siegel Watkins is a thoroughly documented cautionary tale of the information and advice offered to women in the perimenopausal period of their life, and the consequences of exposure to sexual hormones on their health and wellbeing.

The Estrogen Elixir: A History of Hormone Replacement Therapy in America by Elizabeth Siegel Watkins is a thoroughly documented cautionary tale of the information and advice offered to women in the perimenopausal period of their life, and the consequences of exposure to sexual hormones on their health and wellbeing.

The sequencing of the human genome has opened the way for using bioinformatics to identify sets of genes controlled by specific regulatory signals. Here, we review the unexpected diversity of DNA response elements mediating transcriptional regulation by estrogen receptors (ERs), which control the broad physiological effects of estrogens. Consensus palindromic estrogen response elements are found in only a few known estrogen target genes, whereas most responsive genes contain only low‐affinity half palindromes, which may also control regulation by (...) other nuclear receptors. ERs can also regulate gene expression in the absence of direct interaction with DNA, via protein–protein interactions with other transcription factors or by modulating the activity of upstream signaling components, thereby significantly expanding the repertoire of estrogen‐responsive genes. These diverse mechanisms of action must be taken into account in screening for potential estrogen‐responsive sequences in the genome or in regulatory regions of target genes identified by expression profiling. BioEssays 24:244–254, 2002. © 2002 Wiley Periodicals, Inc.; DOI 10.1002/bies.10066. (shrink)

Evidence accumulates that pre- and postnatally circulating estrogens play an active role in the differentiation of the female brain: the susceptible period for feminization of the brain seems to extend far beyond the period during which masculinization of the brain occurs. Thus, there is a need to reevaluate the widely accepted “concept of basic femaleness” in sexual brain differentiation.

The case of Ashley X involved a young girl with profound and permanent developmental disability who underwent growth attenuation using high-dose estrogen, a hysterectomy, and surgical removal of her breast buds. Many individuals and groups have been critical of the decisions made by Ashley's parents, physicians, and the hospital ethics committee that supported the decision. While some of the opposition has been grounded in distorted facts and misunderstandings, others have raised important concerns. The purpose of this paper is to (...) provide a brief review of the case and the issues it raised, then address 25 distinct substantive arguments that have been proposed as reasons that Ashley's treatment might be unethical. We conclude that while some important concerns have been raised, the weight of these concerns is not sufficient to consider the interventions used in Ashley's case to be contrary to her best interests, nor are they sufficient to preclude similar use of these interventions in the future for carefully selected patients who might also benefit from them. (shrink)

In this paper we provide a critical review of research concerned with social/environmental mechanisms that modulate human neuroendocrine function. We survey research in four behavioral systems that have been shaped through evolution: competition, partnering, sex, and pregnancy/parenting. Generally, behavioral neuroendocrine research examines how hormones affect behavior. Instead, we focus on approaches that emphasize the effects of behavioral states on hormones (i.e., the “reverse relationship”), and their functional significance. We focus on androgens and estrogens because of their relevance to sexually selected (...) traits. We conclude that the body of research employing a reversed or bidirectional perspective has an incomplete foundation: participants are mainly heterosexual men, and the functionality of induced shifts in neuroendocrine factors is generally unknown. This area of research is in its infancy, and opportunities abound for developing and testing intriguing research questions. (shrink)

Alzheimer's disease remains the most common form of dementia. Dementia symptoms vary depending on individual personality, life experience, and social and cultural influences. As dementia progresses, involvement of multi-disciplinary health care professionals is needed to manage the disease. Alzheimer research is progressing rapidly. While 5% of all Alzheimer's disease may be genetically determined, the majority is not. Susceptibility genes can reveal the risk of contracting Alzheimer's disease. Early life risk factors such as education, nutrition, and vascular disease may increase the (...) likelihood of dementia in later life. In the United States, two acetylcholinesterase inhibitors have been approved as cognitive enhancers. Possible prevention and symptomatic treatment interventions have focused on estrogen replacement therapy, antioxidants, and anti-inflammatory medications. Research advances have improved the clinical management of dementia. Ethical implications to the patient, family, and society are multiple and remain challenging. (shrink)

Since the 1970s, estrogen have sometimes been used in adolescent girls to reduce very tall adult expected height. Worries about long-term effects have led to a proposal to link treatment data with cancer registers. How should one deal with informed consent for such a study? We designed a qualitative study with semi-structured telephone interviews. From 1200 women who were to be followed-up in cancer registers, we randomly selected 22 women. Major themes were a wish to be involved and a (...) positive attitude to the proposed register research. The women did not express worry after reading the study protocol, but did convey considerable frustration that this research had not been initiated earlier. Active consent was not seen as crucial. We found strong interest in a high participation rate and a concern over missing data. The selection of information and consent or the decision to go ahead without consent in register follow-up is a delicate balancing act. Study participants wish to be contacted, but acknowledge the primary goal of answering important questions. Our study provides support for safeguarding privacy in epidemiological linkage studies and in follow-up of medical treatment without losing the scientific value by requesting for informed consent. (shrink)

We argue that estrogen feminization of the brain is the result of a series of events initiated by differential androgen exposure. There is no need to postulate a feminizing process parallel to androgen-induced masculinization to explain the findings.

Does life have meaning? What is flourishing? How do we attain the good life? Philosophers, and many others of us, have explored these questions for centuries. As Eva Feder Kittay points out, however, there is a flaw in the essential premise of these questions: they seem oblivious to the very nature of the ways in which humans live, omitting a world of co-dependency, and of the fact that we live in and through our bodies, whether they are fully abled or (...) disabled. Our dependent, vulnerable, messy, changeable, and embodied experience colors everything about our lives both on the surface and when it comes to deeper concepts, but we tend to leave aside the body for the mind when it comes to philosophical matters. Disability offers a powerful challenge to long-held philosophical views about the nature of the good life, what provides meaning in our lives, and the centrality of reason, as well as questions of justice, dignity, and personhood. These concepts need not be distant and idealized; the answers are right before us, in the way humans interact with one another, care for one another, and need one another--whether they possess full mental capacities or have cognitive limitations. We need to revise our concepts of things like dignity and personhood in light of this important correction, Kittay argues. This is the first of two books in which Kittay will grapple with just how we need to revisit core philosophical ideas in light of disabled people's experience and way of being in the world. Kittay, an award-winning philosopher who is also the mother to a multiply-disabled daughter, interweaves the personal voice with the philosophical as a critical method of philosophical investigation. Here, she addresses why cognitive disability can reorient us to what truly matters, and questions the centrality of normalcy as part of a good life. With profound sensitivity and insight, Kittay examines other difficult topics: How can we look at the ethical questions regarding prenatal testing in light of a new appreciation of the personhood of disabled people? What do new possibilities in genetic testing imply for understanding disability, the family, and bioethics? How can we reconsider the importance of care, and how does it work best? In the process of pursuing these questions, Kittay articulates an ethic of care, which is the ethical theory most useful for claiming full rights for disabled people and providing the opportunities for everyone to live joyful and fulfilling lives. She applies the lessons of care to the controversial alteration of severely cognitively disabled children known as the Ashley Treatment, whereby a child's growth is halted with extensive estrogen treatment and related bodily interventions are justified. This book both imparts lessons that advocate on behalf of those with significant disabilities, and constructs a moral theory grounded on our ability to give, receive, and share care and love. Above all, it aims to adjust social attitudes and misconceptions about life with disability. (shrink)

Expression of sexually dimorphic behaviors critical for reproduction depends on the organizational actions of steroid hormones on the developing brain. We offer the new hypothesis that transcriptional activities in brain regions executing these sexually dimorphic behaviors are modulated by estrogen‐induced modifications of histone proteins. Specifically, in preoptic nerve cells responsible for facilitating male sexual behavior in rodents, gene expression is fostered by increased histone acetylation and reduced methylation (Me), and, that the opposite set of histone modifications will be found (...) in females. Conversely, in ventromedial hypothalamic neurons that are responsible for coordinating female sexual behavior, transcriptional activities in genetic females are fostered by increased histone acetylation and reduced Me, and, further, that the opposite set of histone modifications will be found in males. Thus, these epigenetic events will guarantee that effects of sex hormone exposure during the neonatal critical period will be translated into lasting sex differences in adult reproductive behaviors. (shrink)

This paper proposes that mammals exhibit three primary emotion categories for mating and reproduction: (1) the sex drive, or lust, characterized by the craving for sexual gratification; (2) attraction, characterized by increased energy and focused attention on one or more potential mates, accompanied in humans by feelings of exhilaration, “intrusive thinking” about a mate, and the craving for emotional union with this mate or potential mate; and (3) attachment, characterized by the maintenance of close social contact in mammals, accompanied in (...) humans by feelings of calm, comfort, and emotional union with a mate. Each emotion category is associated with a discrete constellation of neural correlates, and each evolved to direct a specific aspect of reproduction. The sex drive is associated primarily with the estrogens and androgens; it evolved to motivate individuals to seek sexual union. The attraction system is associated primarily with the catecholamines; it evolved to facilitate mate choice, enabling individuals to focus their mating effort on preferred partners. The attachment system is associated primarily with the peptides, vasopressin, and oxytocin; it evolved to motivate individuals to engage in positive social behaviors and assume species-specific parental duties.During the evolution of the genus Homo, these emotion systems became increasingly independent of one another, a phenomenon that contributes to human mating flexibility and the wide range of contemporary human mating and reproductive strategies. (shrink)

Twenty years ago, Dan Gunther and I published our experience using high-dose estrogen to attenuate the growth of a young girl with severe and permanent neurodevelopmental disability that left her n...

The hygiene hypothesis offers an explanation for the correlation, well-established in the industrialized nations of North and West, between increased hygiene and sanitation, and increased rates of asthma and allergies. Recent studies have added to the scope of the hypothesis, showing a link between decreased exposure to certain bacteria and parasitic worms, and increased rates of depression and intestinal auto- immune disorders, respectively. What remains less often discussed in the research on these links is that women have higher rates than (...) men of asthma and allergies, as well as many auto-immune disorders, and also depression. The current paper introduces a feminist understanding of gender socialization to the epidemiological and immunological picture. That standards of cleanliness are generally higher for girls than boys, especially under the age of five when children are more likely to be under close adult supervision, is a robust phenomenon in industrialized nations, and some research points to a cross- cultural pattern. I conclude that, insofar as the hygiene hypothesis successfully identifies standards of hygiene and sanitation as mediators of immune health, then attention to the relevant patterns of gender socialization is important. The review also makes clear that adding a feminist analysis of gender socialization to the hygiene hypothesis helps explain variation in morbidity rates not addressed by other sources and responds to a number of outstanding puzzles in current research. Alternative explanations for the sex differences in the relevant morbidity rates are also discussed (e.g., the effects of estrogens). Finally, new sources of evidence for the hygiene hypothesis are suggested in the form of cross-cultural and other natural experiments. (shrink)

In Phillip Kerr’s 1994 spellbinding novel A Philosophical Investigation, the medical test to which the protagonist refers is a functional brain scan based on positron emission tomography. It is used to run large studies of male and female brains and, following a lead suggested by animal studies, has been used to identify rare cases of human male subjects who lack the ventral medial nucleus. This nucleus, in the experiment, is hypothesized to inhibit the activity of the sexually dimorphic nucleus, a (...) preoptic area of the male brain believed to be a repository of male aggressive response. Prior research, we learn from the plot, shows that 3 in 100,000 human males are VMN-negative. Thirty percent of those affected are believed to be in prison or to have a criminal record; 70% are believed to stabilize levels of aggression by producing increased levels of estrogen. Identities of subjects participating in the brain scan studies are protected through the conversion of real names to those of famous figures of the past — Bertrand Russell, Charles Dickens. Those for whom results are unfavorable are recontacted, and they are offered counseling. (shrink)

Early in the COVID-19 pandemic, researchers reported a surprising trend in disease outcomes: men were more likely to require hospitalization and die from COVID-19 than women. Researchers looked to sex-linked biology to explain these disparities, hypothesizing innate sex differences in immune function, suggesting the use of estrogens or androgen-suppressants as therapy, and even pushing for sex-specific vaccine strategies. Leading bioethicists like Dr. Ezekiel Emanuel at the University of Pennsylvania recently described the sex disparity in COVID-19 outcomes as "the unsolved mystery" (...) of the... (shrink)

The hypothesis that foreseeable developments in interventions directed to forestall and to treat the disabilities of aging might result in the extension of the human lifespan may be further supported by the “evolutionary theory of aging.” Besides caloric restriction, several hormone supply or replacement strategies are considered to contrast the functional decline associated with aging. Hormone treatments may include growth hormone (GH), insulin‐like growth factor I (IGF‐I) signaling, dehydroepiandrosterone (DHEA), melatonin, testosterone, progesterone, and estrogen. In the 1990s, DHEA was (...) exalted as a possible candidate for the “fountain of youth.” Several experiments on animals have shown that DHEA is a multifunctional adrenal steroid with immune function enhancement, anti‐diabetic, anti‐cancer, and anti‐aging effects. The ethical questions concerning the extension of the lifespan belong to two distinct areas: the area of individual morality and the area of social morality. (shrink)

Breast milk and the placenta are phenomena of female human embodiment that challenge the philosophical notion of separate, sovereign subjects independent of other human be­ings and an objective world “out there.” A feminist phenomenological analysis, indebted to Merleau-Ponty and Irigaray, reveals placenta and milk to be intercorporeal, “chiasmic” forms of shared organic existence. This analysis is a philosophical and psychological exploration of “matrotopy,” i.e., the fact that humans eat their mothers through breast milk and placenta. This exploration, however, requires an (...) understanding of the larger environmental field which sustains the female body and its offspring. Environmental degradation, particularly through estrogen mimicking substances in plastics and pesticides, targets the endocrine system of developing fetuses and endangers the future of the human species from the inside. Invisible organo-chemical technologies pose a new and immediate danger and ethical challenge to women and men in the twenty-first century. A “placental ethics” respects the insertion of the human being into the dynamic field of nature; it calls for an awareness that, unless we develop a changed attitude toward technology, the gradual extinction of our species continues to happen in female bodies today. (shrink)

Female sex steroids can affect the motor system, modulating motor cortex excitability as well as performance in dexterity and coordination tasks. However, it has not yet been explored whether FSS affects the cognitive components of motor behavior. Mu is a sensorimotor rhythm observed by electroencephalography in alpha and beta frequency bands in practices such as motor imagery and action observation. This rhythm represents a window for studying the activity of neural circuits involved in motor cognition. Herein we investigated whether the (...) alpha-mu and beta-mu power in the sensorimotor region and the alpha and beta power over frontal, parietal, and occipital regions are modulated differently in the menstrual, follicular, and luteal phases of menstrual cycles in right-handed dominant women. To do so, these women underwent MI and AO in the three menstrual cycle phases. The spectral activity of the cortical regions for the alpha and beta bands were compared between phases of the menstrual cycle and a correlation analysis was also performed in relation to estrogen and progesterone levels. For the hypothesis-based approach, beta-mu event-related desynchronization was significantly stronger in the C3 channel in the follicular phase than in the menstrual and luteal phases. For the data-driven approach, beta ERD during MI was higher in the follicular phase than in the menstrual and luteal phases in the frontal region. These findings suggest the effect of FSS on executive movement control. No effect of menstrual cycle phases was observed in cortical areas investigated during OA, but alpha and beta bands correlated positively with the follicular phase plasma estradiol level. Thus, the attenuation of alpha and beta bands referring to mirror neuron activities appears to be associated with inhibition of cortical activity when estradiol levels are lower, improving cognitive processing of motor action. (shrink)

Procesy demograficzne można uznać za społeczną konsekwencję podstawowego zjawiska biologicznego – rozmnażania. Nauki społeczne tymczasem pomijają ten wymiar biologiczny lub traktują go apriorycznie jako stałą. W rezultacie swoich prób wyjaśnienia kryzysu demograficznego nauki te umieszczają potencjalnie kluczowe procesy w ich martwym polu. Za stopień determinacji w realizowaniu zamierzeń prokreacyjnych odpowiadają hormony płciowe (testosteron, estrogen), tymczasem rosnąca liczba badań rejestruje narastanie różnego rodzaju negatywnych zjawisk wskazujących na zaburzenie gospodarki tymi hormonami i w rezultacie układu rozrodczego. Choć są to procesy biologiczne, (...) nie mają pochodzenia naturalnego, tj. najprawdopodobniej są rezultatem globalnego rozprzestrzenienia związków endokrynnie aktywnych (EDC). Stanowi to skutek uboczny nieskrępowanego rozwoju technologii możliwego w ramach społeczeństw o organizacji typu produkcyjnego i przy dominacji właściwego temu typowi systemu wartości. (shrink)

The case of Ashley X involved a young girl with profound and permanent developmental disability who underwent growth attenuation using high-dose estrogen, a hysterectomy, and surgical removal of her breast buds. Many individuals and groups have been critical of the decisions made by Ashley's parents, physicians, and the hospital ethics committee that supported the decision. While some of the opposition has been grounded in distorted facts and misunderstandings, others have raised important concerns. The purpose of this paper is to (...) provide a brief review of the case and the issues it raised, then address 25 distinct substantive arguments that have been proposed as reasons that Ashley's treatment might be unethical. We conclude that while some important concerns have been raised, the weight of these concerns is not sufficient to consider the interventions used in Ashley's case to be contrary to her best interests, nor are they sufficient to preclude similar use of these interventions in the future for carefully selected patients who might also benefit from them. (shrink)

For individuals pursuing medically assisted gender transition, gender-affirming surgical treatments, such as oophorectomy (removal of the ovaries) and orchiectomy (removal of the testicles), cause sterility, and gender-affirming hormone treatment with medications (i.e., testosterone and estrogen) may negatively impact infertility. The major United States (US) medical associations already endorse fertility preservation (FP) through cryopreservation (i.e., “freezing” egg and sperm) for transgender individuals. Despite these endorsements from the relevant medical societies, medical insurance coverage for FP remains very limited in the US. (...) Given the high out-of-pocket costs for FP services, fertility preservation remains financially out of reach for many transgender individuals who may desire it. We present an ethical justification for universal FP coverage for all transgender and gender diverse (TGD) individuals who request this option during medically assisted gender transition. First, we argue that gender-affirming medical care is analogous to other medical interventions and treatment regimens that compromise fertility, such as cancer care, and that both types of interventions need to be afforded the same medical benefits and assistance in pursuing fertility goals. Second, we argue that the lack of FP for transgender individuals contributes to the ongoing and profound transphobia and anti-trans bias that has been exacerbated in the past several years across the healthcare landscape in the United States. We argue that the provision of FP coverage for transgender individuals is necessary for clinicians and third-party payers to state their unequivocal support for TGD patients and their healthcare needs. (shrink)

In many species of reptiles, sex is determined at fertilization by zygotic sex chromosome composition. In other species, including all crocodilians, most turtles and some lizards, sex is determined by temperature during the earlier stages of gonadal differentiation. The effects of exogenous estrogens, antiestrogens and aromatase inhibitors at different temperatures have unambiguously demonstrated the involvement of estrogens in sexual differentiation of the gonads. Aromatase is the enzyme that converts androgens to estrogens. Gonadal aromatase activity is well correlated with gonadal structure. (...) It increases exponentially in differentiating ovaries, whereas it remains low in differentiating testes. Moreover, there is a high correlation between the thermosensitive periods for both ovary differentiation and increase in aromatase activity. We suggest that a thermosensitive factor intervenes, directly or indirectly, in the transcriptional regulation of the aromatase gene in reptiles with temperature‐dependent sex determination. (shrink)

A new temperament construct based on recent brain physiology literature has been investigated using the Fisher Temperament Inventory (FTI). Four collections of behaviors emerged, each associated with a specific neural system: the dopamine, serotonin, testosterone, and estrogen/oxytocin system. These four temperament suites have been designated: (1) Curious/Energetic, (2) Cautious/Social Norm Compliant, (3) Analytical/Tough-minded, and (4) Prosocial/Empathetic temperament dimensions. Two functional magnetic resonance imaging (fMRI) studies have suggested that the FTI can measure the influence of these neural systems. In this (...) paper, to further the behavioral validation and characterization of the four proposed temperament dimensions, we measured correlations with five variables: (1) gender; (2) level of education; (3) religious preference; (4) political orientation; (5) the degree to which an individual regards sex as essential to a successful relationship. Subjects were 39,913 anonymous members of a US Internet dating site and 70,000+ members in six other countries. Correlations with the five variables characterize the FTI and are consistent with mechanisms using the proposed neuromodulators. We also report on an analysis between the FTI and the NEO-Five Factor Inventory, using a college sample ( n = 215), which showed convergent validity. The results provide novel correlates not available in other questionnaires: religiosity, political orientation, and attitudes about sex in a relationship. Also, an Eigen analysis replicated the four clusters of co-varying items. The FTI, with its broad systems and non-pathologic factors complements existing personality questionnaires. It provides an index of some brain systems that contribute to temperament, and may be useful in psychotherapy, business, medicine, and the legal community. (shrink)

Open science hardware (OSH) are prototypes of laboratory instruments that use open source hardware to extend the purely epistemic (improving knowledge about nature) and normative (improving society) ideals of science and emphasize the importance of technology. They remind us of Zilsel’s 1942 thesis about the artisanal origins of science and instrument making that bridged disciplinary and social barriers in the 16th century. The emphasis on making, tinkering, and design transcends research, reproducibility, and corroboration in science and pushes to the forefront (...) educational, emancipatory, and aesthetic and exploratory uses. I will use two recent projects, OpenDrop electrowetting platform and Open Source Estrogen that make but also reflect OSH’s playful, expressive, and performative strategies and define the present practices as “artisanal science.” These hybrid and ambiguous practices bridge divides between present disciplines and skills but they also define science as an everyday activity directly connected to the private and public interests of the citizens. To describe this epistemic and normative ambiguity of artisanal science, I employ Hannah Arendt’s 1958 critique of homo laborans and homo faber and claim that science artisans (citizen scientists, geeks, makers, and hackers) offer an alternative to professionalization of science as practiced in the university and R&D laboratories. Science artisans design and build instruments to engage in civic “vita activa” over instruments but also leisurely “otium” outside of the work and science labor. OSH in this sense empowers individuals and communities to explore new connections between scientific practices, public actions, and private interests (leisure). The science artisans strive for and explore sovereignty, dignity, and freedom in an age immersed in science and technology controversies by bridging the divides between art, science, engineering, and humanities. (shrink)

Various explanations have been proposed to account for complex differentiation and development in humans, despite the human genome containing only two to three times the number of genes in invertebrates. Ignored are the actions of adrenal and sex steroids—androgens, estrogens, glucocorticoids, mineralocorticoids, and progestins—which act through receptors that arose from an ancestral nuclear receptor in a protochordate. This ligand‐based mechanism is unique to vertebrates and was integrated into the already robust network of transcription factors in invertebrates. Adrenal and sex steroids (...) influence almost all aspects of vertebrate differentiation and development. I propose that evolution of this ligand‐based mechanism in a primitive vertebrate was an important contribution to vertebrate complexity. Sequencing of genomes from a cephalochordate, such as amphioxus, and from hagfish and lamprey will establish early events in the evolution of steroid hormone signaling, and also allow genetic studies to elucidate how vertebrate complexity depends on steroid hormones. BioEssays 25:396–400, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Abstract11β‐hydroxysteroid dehydrogenases regulate glucocorticoid concentrations and 17β‐hydroxysteroid dehydrogenases regulate estrogen and androgen concentrations in mammals. Phylogenetic analysis of the sequences from two 11β‐hydroxysteroid dehydrogenases and four mammalian 17β‐hydroxysteroid dehydrogenases indicates unusual evolution in these enzymes. Type 1 11β‐ and 17β‐hydroxysteroid dehydrogenases are on the same branch; Type 2 enzymes cluster on another branch with β‐hydroxybutyrate dehydrogenase, 11‐cis retinol dehydrogenase and retinol dehydrogenase; Type 3 17β‐hydroxysteroid dehydrogenase is on a third branch; while the pig dehydrogenase clusters with a yeast multifunctional (...) enzyme on a fourth branch. Pig 17β‐hydroxysteroid dehydrogenase appears to have evolved independently from the other three 17β‐hydroxysteroid dehydrogenase dehydrogenases; in which case, the evolution of 17β‐hydroxysteroid dehydrogenase activity is an example of functional convergence. The phylogeny also suggests that independent evolution of specificity toward C11 substituents on glucocorticoids and C17 substituents on androgens and estrogens has occurred in Types 1 and 2 11β‐ and 17β‐hydroxysteroid dehydrogenases. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Feminist Studies 41, no. 3. © 2015 by Feminist Studies, Inc. 571 Moving through Cancer: An Interview with Carol Collins Artist Carol Collins spoke with Feminist Studies editorial collective member Stephanie Gilmore about her experience of cancer, treatment, and recovery and how it gave rise to an art series that examines what nature means in the midst of unnatural treatments. SG: Carol, thank you for the opportunity to speak (...) with you about your artwork. Having just lost my sister to cancer, your work reminds me of much pain and loss, but also of love and the desire to survive. Before we discuss the work itself, I would like to hear about your journey through cancer, treatment, and recovery. CC: The breast cancer patient’s journey is complex and perilous. When I was healthy, I was ignorant about the magnitude of suffering many cancer patients undergo. And, although I am a private person, I’m now publicly sharing my cancer experience in order to be a voice for those who have suffered through similar treatments—and worse—and those who sadly are no longer with us to tell their story. Being bald and nauseated are not the most awful possible side effects of the treatments, although they are the most well known. Some women survive the cancer but can die from the treatments, or others suffer through the treatments and die anyway. Often, it seems many believe patients can overcome their 572 Carol Collins adversity solely with positive thinking and persistence. However, not discussing the array of physical and psychological damage that even those with good prognoses incur propagates ignorance about this malady. I hope that my artwork and story will promote a deeper understanding of a breast cancer patient’s plight and will encourage more support for research for individualized therapies and prevention. My cancer journey began when I received a breast cancer diagnosis in January 2014. Life just before that point was good; the future was bright. Tendon pain, caused by my flat feet and a lot of exercising, was my only known ailment. But one day a routine mammogram revealed three tumors in my right breast. The radiology oncologist said the masses were highly likely to be cancerous, so he immediately did painful core biopsies at the sites of my three tumors. The next day, it became clear that we needed to act quickly. The biopsy results revealed I had a very aggressive invasive breast cancer with estrogen, progesterone, and HER2 receptors. Breast cancer in premenopausal women grows quickly due to the high level of hormones present. The oncologists and surgeons said I would, at a minimum, need a mastectomy and possibly lymph node resection, and they warned that I would likely need chemotherapy, which would destroy my eggs and ovaries. After learning of my limited options, I approved the removal of one breast and my sterilization. I knew I needed to think rationally and face the giant raven before me head on. However, I did not realize the magnitude and multitude of physical and psychological pains, illnesses, and losses that were soon to come. The first year of cancer treatments inflicted much physical pain. I received three extremely painful injections into my right breast with a radiolabeled colloid just prior to the mastectomy. The pain came from the injected dye, not from the needle. The modified radical mastectomy was more excruciatingly painful than I anticipated, even with painkillers and overnight hospitalization. Breast reconstruction was an option that added more pain and discomfort from weekly fillings of the installed “expander” and additional surgeries. Extreme pain after the mastectomy prevented me from lying down for months. Foolishly, I did not get an injection port installed in my chest. Instead, I endured numerous deep (and often unsuccessful) needle pricks into the seemingly few veins of my left arm (which still had its lymph nodes) that were appropriate for infusions over the period of a year. Shooting pains across my chest and arm were the norm. Carol Collins 573 In addition to the surgically induced physical pain, the chemotherapy quickly caused a myriad of undesirable physical side effects. It is scary to realize that the medical community does not often fully understand... (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Game ChangeMaximo CortezOn November 17, 1983, I was born with a condition called mixed gonadal dysgenesis, and ambiguous genitalia. My gender was not of a big concern at that time. The more urgent matter was that I had a heart murmur, which was repaired when I was twelve months old. [End Page E5]It was not until I turned five, and by issue of the Texas Children’s Protective Services (CPS), (...) that my mother was forced to authorize providers to perform normalization surgeries on me. An anonymous caller tipped the CPS that my mother was raising a boy as a girl. The state intervened and explained to my mother that she would have to consent to these surgeries or else she would lose custody of me. This included a gonadectomy and a clitorectomy. Without any consent, these surgeries were performed “in my best interests.” My mother was an epileptic, Hispanic, Mormon, single parent.I was raised to be a socially acceptable female, though as early as five, I played with “boy” toys and enjoyed TV programs aimed at male youth, like Teenage Mutant Ninja Turtles. It was not until I had those normalization surgeries performed on me that I felt different. I knew that something major had happened to me. I woke up in a hospital bed in a gown. I raised the covers and noticed that I had an “X” carved in my groin area. Doctors mutilated my clitoris by reducing its size, which made me feel alienated and angry that something was wrong with my body.I had a surgery performed on me that was to be kept secret and never talked about. This sense of fear and shame was instilled in me shortly after the surgery. I do not recall any psychological evaluations or counseling to help me cope with such surgeries. Seeing everyone else my age going through puberty during my teenage years, I felt behind. I wasn’t becoming a boy with a deep voice or facial hair. Instead, I visited the doctor’s office with my mom and was told that I would be taking oral estrogen to become a woman. I wasn’t until that moment that I understood I was seeing a doctor to foster the development of female secondary characteristics. I felt betrayed by the medical community and by my own mother.Just a few years later, I saw a urologist to find out whether I was ready for a vaginal construction surgery (vaginoplasty). Thankfully the urologist suggested that I was not ready to move forward with an invasive and irreversible vaginal construction surgery. I never pursued it as an adult, as I have always felt male gendered.Social sexual relationships have always been difficult for me but more so with my attraction to women. I first realized my attraction to women in early middle school. Being raised Mexican and a Mormon and knowing that I was homosexual created a lot of conflict for me. I felt that I was a male–gendered person forced into a castrated, mutilated, and medically created female body. I suffered through depression from an early age and it continues today. My conservative Mormon upbringing brought me much shame. The Mormon religion, as most people understand it, expresses a great intolerance to homosexuals and transgender people. I felt like I was a heterosexual male in a female’s body, but the Mormons would never accept me.My later teenage years and mid–twenties were a dark time in my life. I even attempted suicide in my early twenties. My depression was treated with antidepressants and talk therapy. Once I began testosterone, I gradually stopped taking antidepressants. When I was only on estrogen, I felt very moody, angry, and in an emotional funk. I would cry easily and would become very irritable and emotional without cause. With testosterone therapy, I began to think more clearly, had balanced emotions, and began to think more logically.I began to research intersex online and found a women’s androgen insensitivity (AIS) support group. At one of their national conferences, I met another intersex individual who was raised as a female and who had transitioned to male. Like me... (shrink)

Researches over many years have examined whether levonorgestrel emergency contraception has a postfertilization effect. In a recent article in the Catholic Health Association’s journal Health Progress, Sandra Reznik, MD, asserts that “levonorgestrel acts to prevent pregnancy before, and only before, fertilization occurs.” A companion article by Ron Hamel, PhD, argues for the moral certainty that Plan B is not an abortifacient. Reznik fails to address the principal model supporting a potential postfertil­ization mechanism of action, specifically, that preovulatory administration of levonorgestrel (...) disrupts the delicate ratio of estrogen and progesterone essential to healthy endometrial development and induces the equivalent of luteal phase insufficiency, thereby jeopardizing implantation. Hamel’s argument for moral certitude is similarly inadequate. This article critically reviews both articles and the sources on which they rely. National Catholic Bioethics Quarterly 10.4 : 741–772. (shrink)

A number of commentators agree that the evidence reviewed in the target article supports a previously unrecognized role for ovarian hormones in feminization of the brain. Others question this view, suggesting that the traditional model of sexual differentiation already accounts for ovarian influence. This position is supported by various reinterpretations of the data presented (e.g., ovarian effects are secondary to the presence/absence of androgen, ovarian effects are smaller than testicular effects, ovarian effects are not organizational). We discuss these issues, and (...) reiterate our position that evidence of neurobehavioral ovarian effects is incompatible with the currently accepted model of sexual differentiation. Other points regarding species generalizations, the direct versus indirect action of estrogen, and nonhormonal mechanisms of sexual differentiation are also discussed. Finally, we address the controversial issue of using ratio scores in the assessment of the human corpus callosum (where CC scores are divided by an index of brain size). Future applications to human research are also discussed. (shrink)

Current clinical guidelines for the treatment of individuals who experience gender dysphoria include the administration of testosterone to women who desire to appear as men and estrogen to men who desire to appear as women. Despite the rapid and widespread adoption of this practice, strikingly little scientific evidence supports this treatment approach as a safe and effective medical intervention to prevent associated depression and suicide. Although low-quality, short-term studies have demonstrated a reduction of dysphoria, emerging evidence reveals significant bodily (...) harm from this practice and a lack of long-term benefit in preventing depression and suicide. From an ethical perspective, this practice distorts a proper view of human nature and violates bodily integrity by directly inducing sterility. The use of exogenous cross-sex hormones reinforces rather than alleviates underlying psychiatric dysfunction while significantly increasing the risk of other medical morbidities. Despite the valid goal of alleviating suffering, this practice cannot be justified by the use of the principles of totality or double effect. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Transgressive Translations:Parrhesia and the Politics of Being UnderstoodTim R. JohnstonAuthor And Activist Julia Serano’s spoken word poem “Performance Piece” is a smart and passionate polemic against people who say that “all gender is performance” (Serano 2010, 85). In response to those who treat gender as an endlessly mutable fiction, performance, or facade Serano says:Sure, I can perform gender: I can curtsy, or throw like a girl, or bat my (...) eyelashes. But performance doesn’t explain why certain behaviors and ways of being come to me more naturally than others. It offers no insight into the countless restless nights I spent as a pre-teen wrestling with the inexplicable feeling that I should be female. It doesn’t capture the very real physical and emotional changes that I experienced when I hormonally transitioned from testosterone to estrogen. (Serano 2010, 85–86)My first reaction to this understanding of performativity was to get defensive, immediately thinking of all the ways in which it reflects a poor reading of Judith Butler and is an incorrect use of the concept. Yet, to make that argument would mean arriving late to the party. Many theorists, notably Jay Prosser and Viviane Namaste, have made similar arguments about performativity to which Butler and many others have responded. I am not interested in joining this debate by defending or critiquing performativity; instead, I want to take seriously Serano’s criticism of the way performativity functions as a “mantra” for [End Page 84] “queerer-than-thou hipsters” (Serano 2010, 87). The fact is, concepts that help people make sense of their experience are often taken up piecemeal. They gain traction, get printed on posters, discussed in safe-spaces, taught in intro classes, and yelled at parents. They take on a life of their own and are queered again and again. It may not be anyone’s fault that performativity has come to signify a kind of insincerity, detachment from the body, linguistic constructionism, or a play of surfaces, but for many people this is exactly what it means. What follows is inspired by the questions at the heart of Serano’s poem: “Can’t we find new ways of speaking? Shouldn’t we be championing new slogans that empower all of us, whether trans or non-trans, queer or straight, female and/or male and/ or none of the above?” (Serano 2010, 87). I depart slightly from Serano insofar as I am not interested in replacing performativity as a concept. Instead, I am interested in locating other concepts that could be useful in understanding and communicating our multiple experiences of gender.Serano’s concern is not only the depth and conviction with which she experiences gender, but also the communicability of this conviction. We are social beings. We seek out the company of other people, animals, and objects. In order to flourish we need to feel understood by our surroundings. We are creatures that need to be connected, and connection requires translating our subjective experiences into a communicable, socially understandable register. How does this translation occur? How do we make ourselves understandable? What external forces regulate or influence this translation? And, crucially, how can we construct philosophical concepts that do justice to our need to feel that our interior selves are understood? What concept could we cast out into the world that might answer Serano’s call for new ways of speaking? What follows is an attempt to think through this question by looking at the relationship between the medicalization of trans people, Michel Foucault’s writings on parrhesia, and coming out.The first half of this essay examines the ways in which the medical apparatus that manages transitioning attempts to control transsexual coming-out narratives, an example of what Foucault calls biopower. I argue that the medicalization of transitioning has created a legible transsexual identity structured on the distance between our interiority and the world external to the self. The trans person’s claims about their interior sense of self are the only evidence needed to access medical technologies such as hormone therapy or surgery. But oftentimes such claims are only accepted as valid if they conform to certain scripts—scripts that are... (shrink)

Developmental counts of axons in the splenium of the rat corpus callosum are compatible with the hypothesis that estrogen may be acting late in development to sculpt the female nervous system.

Alpha‐fetoprotein (AFP)AFP, alpha‐fetoprotein; T3R, thyroid hormone (triiodothyronine) receptor; RAR, retionic acid receptor; erbA, putative thyroid hormone receptor proto‐oncogene products; VDR, vitamin D receptor; MR, mineralocorticoid receptor; GR, glucocorticoid receptor; PR, progesterone receptor; AR, androgen receptor; HRE, hormone response element on DNA; RXR, retionic‐X‐receptor; RAP, receptor auxiliary (accessory) proteins; E, estrogen. is a tumor‐associated fetal marker, associated both with tumor growth and with birth defects. AFP, whose precise function is unknown, has been classified as belonging to a protein superfamily together (...) with albumin and vitamin D‐binding (Gc) protein. AFP has been shown to bind various ligands in vitro including fatty acids, estrogens, thyroid hormones and retinoic acids. The steroid/thyroid nuclear receptor superfamily of proteins has recently become a major focus of biomedical investigation regarding regulation of gene expression. These receptors are thought to bind to DNA‐hormone response elements (HRE) that affect growth, development, differentiation, reproduction and homeostasis. The HREs are known to share DNA sequences with the various members of the nuclear receptor superfamily. In the present report, the possibility of a leucine‐zipper dimerization (heptad) motif in the carboxy‐terminal third domain of both rodent and human AFP is postulated. The presence of nine such hydrophobic repeats in the third domain of the AFP molecule mimics the heptad dimerization repeats found in the retinoic acid, thyroid, e‐erbA and other members of the nuclear receptor superfamily. Computer analysis revealed that the most conservative matching occurred between AFP and the retinoic acid class of receptors. However, other superfamily members displayed 40–60% homology with 5 of 9 AFP heptads. These findings could provide a possible mechanism for explaining the growth‐regulatory properties (both inhibition and enhancement) that have been ascribed to AFP in the last decade. (shrink)

IT sounds like something out of the satirical journal Annals of Improbable Research: a team of Swedish neuroscientists scanned people's brains as they smelled a testosterone derivative found in men's sweat and an estrogen-like compound found in women's urine. In heterosexual men, a part of the hypothalamus (the seat of physical drives) responded to the female compound but not the male one; in heterosexual women and homosexual men, it was the other way around. But the discovery is more than (...) just a shoo-in for that journal's annual Ig Nobel Prize - it raises provocative questions about the science and ethics of human sexuality. (shrink)