Understanding the broad influence of sex hormones and sex differences in the brain.

Sex hormones act throughout the entire brain of both males and females via both genomic and nongenomic receptors. Sex hormones can act through many cellular and molecular processes that alter structure and function of neural systems and influence behavior as well as providing neuroprotection. Within neurons, sex hormone receptors are found in nuclei and are also located near membranes, where they are associated with presynaptic terminals, mitochondria, spine apparatus, and postsynaptic densities. Sex hormone receptors also are found in glial cells. Hormonal regulation of a variety of signaling pathways as well as direct and indirect effects on gene expression induce spine synapses, up- or downregulate and alter the distribution of neurotransmitter receptors, and regulate neuropeptide expression and cholinergic and GABAergic activity as well as calcium sequestration and oxidative stress. Many neural and behavioral functions are affected, including mood, cognitive function, blood pressure regulation, motor coordination, pain, and opioid sensitivity. Subtle sex differences exist for many of these functions that are developmentally programmed by hormones and by not yet precisely defined genetic factors, including the mitochondrial genome. These sex differences and responses to sex hormones in brain regions, which influence functions not previously regarded as subject to such differences, indicate that we are entering a new era of our ability to understand and appreciate the diversity of gender-related behaviors and brain functions. © 2016 Wiley Periodicals, Inc.

[Naming and classification of steroids and human stress ulcers. Articles of historic significance published by Hans Selye 70 years ago]. / A szteroidok elnevezése, felosztása és az emberi stresszfekélyek. Selye János 70 éve megjelent történelmi jelentoségu cikkei.

The name of Hans Selye is mostly known worldwide as the discoverer of stress reaction. Yet, he made numerous other seminal and clinically relevant discoveries. Namely, since he had a focused research on steroid hormones originating from the adrenal cortex that play a crucial role in stress response, he was the first who introduced about 70 years ago the first classification of steroids that is still valid nowadays. This is based on three objective facts: (a) the names of steroid groups are identical with their organ of origin (e.g., corticoids from the adrenal cortex, testoids/androgens from the testis); (b) chemical structures of the steroids are identical within a group (e.g., all corticoids have pregnane nucleus with 21 carbon atoms); and (c) the biological effects are homogenous within a group (e.g., all glucocorticoids exert catabolic effect, while androgens are anabolic). It should be emphasized that Selye also discovered in animal models the pro-inflammmatory effect of mineralocorticoids and the anti-inflammatory properties of glucocorticoids, about 8-10 years before Nobel Prize was awarded to a physician for the first clinical use of adrenocorticotrop hormone and cortisone. Last, but not least, Selye was the first who recognized about 70 years ago the occurence of stress ulcers in humans, based on clinical reports on the huge increase in the number of perforated gastric anti-duodenal ulcers during bombings of London in World War II. The subsequent ulcer research by Selye`s former students and their contemporaries resulted in the recognition of anti-duodenal ulcer effect of dopamine, and the central gastroprotective actions of thyreotrop releasing hormone and endogenous opioids. Thus, Hans Selye made much more contributions to medical science and clinical practice than 'just' the discoverer of biologic stress response.

The classic: the metabolic effects of steroid hormones in osteoporosis. 1946.

This Classic Article is a reprint of the original work by E.C. Reifenstein Jr. and F. Albright, The Metabolic Effects of Steroid Hormones in Osteoporosis. An accompanying biographical sketch of F. Albright is available at DOI 10.1007/s11999-011-1831-0 . The Classic Article is ©1946 and is reprinted with permission from The American Society for Clinical Investigation from Reifenstein EC, Albright F. The metabolic effects of steroid hormones in osteoporosis. J Clin Invest. 1947;26:24-56.

[The reign of hormones and the construction of gender differences]. / O império dos hormônios e a construção da diferença entre os sexos.

Within the context of the theoretical debate on gender and science, the article discusses the process of redefining gender and sex differences using so-called biological or natural markers. It identifies how gender differences undergo naturalization using a logic of 'substantialization or 'materialization'. This process is exemplified in how medicine views women, promoting explanatory models of economics of the female body that are at times centered around organs like the uterus and ovaries, at other times centered on the mechanics of hormones, and, most recently, focused on genetic and neurological differences. More specifically, it follows the discovery of so-called sex hormones and its relation to a dualist perspective of gender. These powerful chemical messengers helped shaped the passage from the logic of excess surrounding sex through the late nineteenth century, to the imperative of insufficiency, prevalent since the mid-twentieth century.

Steroids and endocrine disruptors--History, recent state of art and open questions.

This introductory chapter provides an overview of the levels and sites at which endocrine disruptors (EDs) affect steroid actions. In contrast to the special issue of Journal of Steroid Biochemistry and Molecular Biology published three years ago and devoted to EDs as such, this paper focuses on steroids. We tried to point to more recent findings and opened questions. EDs interfere with steroid biosynthesis and metabolism either as inhibitors of relevant enzymes, or at the level of their expression. Particular attention was paid to enzymes metabolizing steroid hormones to biologically active products in target cells, such as aromatase, 5α-reductase and 3ß-, 11ß- and 17ß-hydroxysteroid dehydrogenases. An important target for EDs is also steroid acute regulatory protein (StAR), responsible for steroid precursor trafficking to mitochondria. EDs influence receptor-mediated steroid actions at both genomic and non-genomic levels. The remarkable differences in response to various steroid-receptor ligands led to a more detailed investigation of events following steroid/disruptor binding to the receptors and to the mapping of the signaling cascades and nuclear factors involved. A virtual screening of a large array of EDs with steroid receptors, known as in silico methods (≡computer simulation), is another promising approach for studying quantitative structure activity relationships and docking. New data may be expected on the effect of EDs on steroid hormone binding to selective plasma transport proteins, namely transcortin and sex hormone-binding globulin. Little information is available so far on the effects of EDs on the major hypothalamo-pituitary-adrenal/gonadal axes, of which the kisspeptin/GPR54 system is of particular importance. Kisspeptins act as stimulators for hormone-induced gonadotropin secretion and their expression is regulated by sex steroids via a feed-back mechanism. Kisspeptin is now believed to be one of the key factors triggering puberty in mammals, and various EDs affect its expression and function. Finally, advances in analytics of EDs, especially those persisting in the environment, in various body fluids (plasma, urine, seminal fluid, and follicular fluid) are mentioned. Surprisingly, relatively scarce information is available on the simultaneous determination of EDs and steroids in the same biological material. This article is part of a Special Issue entitled 'Endocrine disruptors & steroids'.

Better prepared than synthesized: Adolf Butenandt, Schering Ag and the transformation of sex steroids into drugs (1930-1946).

This paper follows the trajectory of sex steroids in 1930s Germany as a way to investigate the system of research which characterized the development of these drugs. Analyzing the changing relationship between the pharmaceutical company Schering and the Kaiser Wilhelm Institute für Biochemie headed by Nobel Prize winner Adolf Butenandt, the paper highlights the circulation of materials, information and money as much as the role of patents in shaping the study of sex steroids. Semi-synthetic analogs and metabolic pathways thus emerged as shared bio-industrial assets. This collaborative work participated in a more general 'internalization' of biology, which took place in pharmaceutical firms during the 1920s and 1930s as a strategy to standardize and develop biologicals. The construction of the hormone market was also based on Schering's collaboration with a selected group of clinicians who worked out the wide-range of indications associated with these 'natural' drugs. The paper finally shows how the wartime scientific and industrial mobilization in Nazi Germany marginalized the study of sex steroids and led to the dismantling of the KWIB-Schering network.

Uncommon trajectories: steroid hormones, Mexican peasants, and the search for a wild yam.

This article analyzes how evolving pharmaceutical technology, chemical advances, and world politics created the need for an abundant and cheap supply of steroids, and how decisions made in faraway laboratories ultimately determined that a Mexican yam, barbasco, was the best possible raw material. Following this discovery, this article explores how barbasco's exploitation impacted on the Mexican countryside and specifically the men and women hired to gather wild yams. In analyzing, for example, the peasant organizations that emerged, the use of chemical terms by barely literate peasants, and the Mexican government's political strategy to control rural unrest by controlling barbasco production one begins to understand the unexpected consequences of the global search for medicinal plants. In this particular case, the merging of science and peasant life reshuffled social hierarchies in the countryside, granted monetary value to an erstwhile 'weed', and gave a novel reinterpretation to laboratory knowledge and its (social) uses.

An abridged history of sex steroid hormone receptor action.

The field of steroid hormone action is well established, although it is barely more than four decades old. Pivotal experiments in the late 1950s and 1960s showed that hormone-binding components exist within nuclei of target tissues and that steroid hormones act by regulating gene expression, rather than directly influencing enzymatic processes. The understanding that steroid hormone receptors interact with the general transcription machinery and alter chromatin structure came in the 1970s and 1980s, and details of this mechanism continue to be elucidated. In addition, the discovery of rapid cellular responses to steroid hormones has led to the identification of putative membrane-bound steroid receptors that act without affecting gene transcription. As noted in the recent Institute of Medicine report "Exploring the Biological Contributions to Human Health: Does Sex Matter?", the effects of steroid hormones and defects in steroid hormone receptor action have a profound impact on human health and disease. Future research directives include the development of potent, selective steroid receptor modulators, the elucidation of nongenomic steroid hormone effects, and further exploration of hormone-genome interactions.

Menopause, only for women? The social construction of menopause as an exclusively female condition.

Over the last three decades the menopause has continued to interest the medical profession, the pharmaceutical industry and the mass media. Although there exist many different views on the menopause, there is one common denominator. Menopause is depicted as an exclusively female condition. The medical discourse on menopause seems to exclude men. However, a closer look at the history of the medical sciences reveals that there have been and still are, attempts to classify symptoms of ageing men as male menopause or climacterium. Despite these attempts to put men on the menopausal agenda, most attention is focused on women. How can we understand this almost exclusive focus on female bodies? Why does there exist such an emphasis on the medicalization of the third age of women rather than of men? Maybe we might be inclined to think of a male conspiracy, as has been suggested by feminists: women take the pills, while men cash the bills. We might consider the enormous profits of the pharmaceutical industry. This paper is concerned with finding an alternative explanation for the almost exclusive attention for the female menopause. Based on historical data and more recent discussions in medical journals, the paper shows that the medicalization of the female menopause and the relative silence around the male climacterium can be understood in terms of the social and cultural processes that underly the classification of health problems as specific diseases. The imbalance in medical treatment of climacteric health problems in women and men is not simply rooted in biological sex differences, but can be ascribed to men's attitudes towards health problems and organizational infrastructures of the medical institutions.

On the history of biological theories of homosexuality.

Biological theories of homosexuality fit into the discourse on reproduction and sexuality that began in the nineteenth century. They arose in the context of the early homosexual rights movement, with its claim for natural rights, and the psychiatric discussions about sexual perversions. With the classification of homosexuality as a distinct category, homosexuals were excluded from the "normal". Biological theories of homosexuality were attempts not only to explain its causes, but also to maintain the exclusion of homosexuals as the "other". Biological explanations can be categorized as genetic, constitutional, endocrinological, and ethological. On the one hand, biological theories were used in the struggle for homosexual rights. On the other hand, they were used to "cure"e homosexuals. Every theory led to a specific therapy. This paper points out the roots of this thinking, traces the development of various theories, and shows the utilization of biological theories in treating homosexuality.

[Growth factors in the uterus are surveyed]. / Tillväxtfaktorer i livmodern kartläggs.

The central localisation of the uterus in the female body may be seen as reflecting its central function in human reproduction, though in rare cases pregnancy may be established even in the absence of uterus. The sex steroids are largely responsible for the central regulation of uterine function, and recent productive research has shown the significance of peptide growth factors for various physiological functions, including the development and repair of the endometrium during the menstrual cycle, as well as the adaptation and growth of the organ during pregnancy. The possible involvement of angiogenic peptides in endometrial neovascularisation is discussed, as is the significance of proto-oncogenes and growth factors for the development of uterine fibroids. Further development in this field may have a variety of clinical implications, including the possibility of promoting or inhibiting implantation by manipulation of endometrial angiogenesis.

[Laqueur and Organon. The university laboratory and the pharmaceutical industry in the Netherlands]. / Laqueur en Organon. Het universitaire laboratorium en de farmaceutische industrie in Nederland.

Since the 1970s cooperation between universities and pharmaceutical firms is business as usual. This has not always been the case. The first alliances between academic scientists and the pharmaceutical industry can be traced back to the 1920s. Compared to the U.S. and most other European countries, the creation of networks between the Dutch academy and industry shows a rather peculiar pattern that is illustrative in clarifying how the relationships between scientists and the pharmaceutical companies were built. Dutch scientists could not ally themselves with the pharmaceutical industry, simply because no Dutch pharmaceutical company specialized in organpreparations existed prior to the 1920s. This situation forced scientists to opt for the strongest form of alliance they could create, namely to take part in the founding of a pharmaceutical company. Ernst Laqueur, a professor in pharmacology at the University of Amsterdam, was one of the three founders of Organon, the Dutch pharmaceutical firm that was founded in 1923. Based on an analysis of the early history of sex endocrinology, this paper examines the creation of networks between Laqueur and Organon. The paper concludes that the university laboratory played a crucial role in the development of Organon. Organon was dependent on Laqueurs laboratory for the provision of the required biological essay techniques in order to manufacture standardized hormone products, Moreover, Laqueur mediated all the contacts between Organon and the clinic, required for the clinical testing of hormones and the provision of raw materials for the making of hormones into chemicals and drugs.

Absorção e metabolização dos hormônios sexuais e sua transformação em tecnologias contraceptivas: percursos do pensamento médico no Brasil / Absorption and metabolization of sex hormones and their transformation into contraceptive technologies: the paths taken by medical thought in Brazil

O artigo analisa a assimilação de conhecimentos e o desenvolvimento de práticas clnicas e de pesquisa, concernentes aos hormônios sexuais, entre ginecologistas brasileiros. Discute o percurso do pensamento médico da recepção dos hormônios à sua transformação em contraceptivos. O objetivo é compreender estilos de introdução e difusão de tecnologias médicas na área da saúde reprodutiva no Brasil. Utiliza métodos de análise histórica e tem como fonte os Anais Brasileiros de Ginecologia, revista publicada entre 1936 e 1970. O acompanhamento das novidades cientificas sobre hormônios sexuais e seu uso para tratamento de diversas mazelas femininas, desde os primórdios, foi de grande importância para a rápida aceitação médica da contracepção hormonal. Questões científicas e técnicas (efeitos colaterais, dosagens) e a questão populacional compuseram a maior parte dos debates. Objeções da Igreja Católica foram consideradas, mas não pautaram o pensamento médico sobre os contraceptivos. A busca de consolidar a ginecologia como especialidade científica, moderna e cosmopolita e razões sanitárias e demográficas que possibilitavam enquadrar contraceptivos como drogas éticas, são processos subjacentes à assimilação e à metabolização dos hormônios sexuais como contraceptivos hormonais.

Injection, ligation and transplantation: the search for the glandular fountain of youth.

PURPOSE: During the 19th and early 20th centuries there was great interest in antiaging remedies. This search for the eternal fountain of youth stemmed from the concept of aging as a pathological condition that destroyed the body and mind. In addition, great emphasis was placed on the economic challenge that the elderly presented to society. We examine the history of antiaging therapies from the perfection of cell nutrition to glandular transplants. MATERIALS AND METHODS: A literature review was performed including direct first person sources such as historical documents, letters of correspondence, newspaper articles and journal publications. Historical texts were also consulted for accuracy. RESULTS: The history of antiaging medicine includes a variety of remedies. E. Metchnikoff advocated a diet rich in lactic acid which he thought would eradicate the body of intestinal putrefaction and decay. Others believed the fountain of youth lay within the endocrine system. C. E. Brown-Sequard linked the decrease in sexual function with the aging body and claimed he could restore a youthful state with the injection of a mixture of animal sex glands. The compound Spermine was subsequently marketed as an injection that promised the effects observed by Brown-Sequard. The early 20th century was marked by a number of surgical attempts at the restoration of youth. L. L. Stanley reported on more than 643 inmates at the San Quentin prison on whom he had performed testicular transplantation. This idea of gland grafting gained international interest and led others such as S. Voronoff to experiment with the transplantation of various animal glands into humans. In addition to gland grafting, vasoligation was advocated by E. Steinach in an effort to direct sperm from the testicles back to the body. The Steinach operation was claimed to restore youth and vigor. Although most physicians directed their attention toward remedies for men, some came to advocate remedies for women including ovarian transplantation and radiation. CONCLUSIONS: The search for the glandular fountain of youth ultimately led to the discovery of testosterone. The modern day interest in plastic surgery, testosterone replacement and growth hormone injection underscores the concept of aging as a disease process. We have yet to determine whether aging represents physiology or pathology. However, it is certain that the search for the fountain of youth will continue.

[The single hormone hypothesis. An instructive episode in the history of ovarian endocrinology]. / Die Ein-Hormon-Hypothese. Eine aufschlussreiche Episode in der Geschichte der Ovarialendokrinologie.

In the mid-twenties of the present century renowned scientists held the opinion that only one female sex hormone is secreted by the ovary. A survey is given how this hypothesis arose, for which reasons it was favoured and why it had to be given up. The importance of the Allen-Doisy test (1923) and the Corner-Allen test (1929) and of the publications by these authors is stressed. Finally, it is shown that Thomas S. Kuhn's theory, explaining how scientific advance is promoted by changing a paradigm, is also applicable to this phase of research in ovarian endocrinology as well.