Recent progress in hormone research最新文献

{"title":"Identification of specific sites of hormonal regulation in spermatogenesis in rats, monkeys, and man.","authors":"R. McLachlan, L. O’Donnell, S. Meachem, P. Stanton, deKretser Dm, K. Pratis, D. Robertson","doi":"10.1210/RP.57.1.149","DOIUrl":"https://doi.org/10.1210/RP.57.1.149","url":null,"abstract":"A detailed understanding of the hormonal regulation of spermatogenesis is required for the informed assessment and management of male fertility and, conversely, for the development of safe and reversible male hormonal contraception. An approach to the study of these issues is outlined based on the use of well-defined in vivo models of gonadotropin/androgen deprivation and replacement, the quantitative assessment of germ cell number using stereological techniques, and the directed study of specific steps in spermatogenesis shown to be hormone dependent. Drawing together data from rat, monkey, and human models, we identify differences between species and formulate an overview of the hormonal regulation of spermatogenesis. There is good evidence for both separate and synergistic roles for both testosterone and follicle-stimulating hormone (FSH) in achieving quantitatively normal spermatogenesis. Based on relatively selective withdrawal and replacement studies, FSH has key roles in the progression of type A to B spermatogonia and, in synergy with testosterone, in regulating germ cell viability. Testosterone is an absolute requirement for spermatogenesis. In rats, it has been shown to promote the adhesion of round spermatids to Sertoli cells, without which they are sloughed from the epithelium and spermatid elongation fails. The release of mature elongated spermatids from the testis (spermiation) is also under FSH/testosterone control in rats. Data from monkeys and men treated with steroidal contraceptives indicate that impairment of spermiation is a key to achieving azoospermia. The contribution of 5alpha-reduced androgens in the testis to the regulation of spermatogenesis is also relevant, as 5alpha-reduced androgens are maintained during gonadotropin suppression and may act to maintain low levels of germ cell development. These concepts are also discussed in the context of male hormonal contraceptive development.","PeriodicalId":21099,"journal":{"name":"Recent progress in hormone research","volume":"1510 1","pages":"149-79"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77716363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aromatase and its inhibitors: significance for breast cancer therapy.","authors":"E. Simpson, M. Dowsett","doi":"10.1210/RP.57.1.317","DOIUrl":"https://doi.org/10.1210/RP.57.1.317","url":null,"abstract":"Endocrine adjuvant therapy for breast cancer in recent years has focussed primarily on the use of tamoxifen to inhibit the action of estrogen in the breast. The use of aromatase inhibitors has found much less favor due to poor efficacy and unsustainable side effects. Now, however, the situation is changing rapidly with the introduction of the so-called phase III inhibitors, which display high affinity and specificity towards aromatase. These compounds have been tested in a number of clinical settings and, almost without exception, are proving to be more effective than tamoxifen. They are being approved as first-line therapy for elderly women with advanced disease. In the future, they may well be used not only to treat young, postmenopausal women with early-onset disease but also in the chemoprevention setting. However, since these compounds inhibit the catalytic activity of aromatase, in principle, they will inhibit estrogen biosynthesis in every tissue location of aromatase, leading to fears of bone loss and possibly loss of cognitive function in these younger women. The concept of tissue-specific inhibition of aromatase expression is made possible by the fact that, in postmenopausal women when the ovaries cease to produce estrogen, estrogen functions primarily as a local paracrine and intracrine factor. Furthermore, due to the unique organization of tissue-specific promoters, regulation in each tissue site of expression is controlled by a unique set of regulatory factors. These factors are potential targets for the design of selective aromatase modulators, which could selectively inhibit aromatase expression in breast with the same efficacy as the phase III inhibitors of activity but leave expression in other local sites such as bone and brain untouched.","PeriodicalId":21099,"journal":{"name":"Recent progress in hormone research","volume":"7 1","pages":"317-38"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73128381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Male germ cell gene expression.","authors":"E. M. Eddy","doi":"10.1210/RP.57.1.103","DOIUrl":"https://doi.org/10.1210/RP.57.1.103","url":null,"abstract":"Formation of the male gamete occurs in sequential mitotic, meiotic, and postmeiotic phases. Many germ cell-specific transcripts are produced during this process. Their expression is developmentally regulated and stage specific. Some of these transcripts are product of genes that are male germ cell-specific homologs of genes expressed in somatic cells, while some are expressed from unique genes unlike any others in the genome. Others are alternate transcripts derived from the same gene as transcripts in somatic cells but differing from them in size and/or overall sequence. They are generated during gene expression by using promoters and transcription factors that activate transcription at different start sites upstream or downstream of the usual site, by incorporation of alternate exons, by germ cell-specific splicing events, and by using alternate initiation sites for polyadenylation. Male germ cell development consists of an assortment of unique processes, including meiosis, genetic recombination, haploid gene expression, formation of the acrosome and flagellum, and remodeling and condensation of the chromatin. These processes are intricate, highly ordered, and require novel gene products and a precise and well-coordinated program of gene expression to occur. The regulation of gene expression in male germ cells occurs at three levels: intrinsic, interactive, and extrinsic. A highly conserved genetic program \"intrinsic\" to germ cells determines the sequence of events that underlies germ cell development. This has been underscored by recent studies showing that meiosis involves many genes that have been conserved during evolution from yeast to man. During meiosis and other processes unique to germ cells, the intrinsic program determines which genes are utilized and when they are expressed. In the postmeiotic phase, it coordinates the expression of genes whose products are responsible for constructing the sperm. The process of spermatogenesis occurs in overlapping waves, with cohorts of germ cells developing in synchrony. The intrinsic program operating within a particular germ cell requires information from and provides information to neighboring cells to achieve this coordination. Sertoli cells are crucial for this \"interactive\" process as well as for providing essential support for germ cell proliferation and progression through the phases of development. The interactive level of regulation is dependent on \"extrinsic\" influences, primarily testosterone and follicle-stimulating hormone (FSH). Studies during the last 4 years have established that FSH is not essential for germ cell development but instead serves an important supportive role for this process. While testosterone is essential for maintenance of spermatogenesis, it acts on Sertoli cells and peritubular cells and has indirect effects on germ cells. The extrinsic and interactive processes are extremely important for establishing and maintaining an optimum environment within which gametog","PeriodicalId":21099,"journal":{"name":"Recent progress in hormone research","volume":"8 1","pages":"103-28"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78630030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of hormonal and reproductive factors in the etiology and treatment of uterine leiomyoma.","authors":"C. Walker","doi":"10.1210/RP.57.1.277","DOIUrl":"https://doi.org/10.1210/RP.57.1.277","url":null,"abstract":"Uterine leiomyomas are the most common gynecologic neoplasm in reproductive-age women. While it is clear that hormonal factors play a prominent role in this disease, how steroid hormones contribute to disease etiology or may be utilized as targets for intervention are currently areas of active scientific investigation. To study the impact of hormones on uterine leiomyomas, the Eker rat has been developed as an in vivolin vitro animal model system for these tumors. Spontaneous leiomyomas arise in intact Eker rats with a high frequency and leiomyoma-derived cell lines from these animals maintain the biochemical and physiological characteristics of the tumors from which they were obtained. Using this animal model system, it has been established that tumor development is absolutely dependent on steroid hormones and that sensitivity/responsiveness to estrogen is enhanced in tumors and tumor-derived cell lines. Modulation of hormonal milieu, such as that which naturally occurs during pregnancy, can effectively inhibit tumor development. The hormone responsiveness of these tumors makes them good candidates for hormonal therapy. Selective estrogen receptor modulators (SERMs) tamoxifen and raloxifene hold promise as potential therapeutic agents for this disease. SERMs inhibit proliferation of leiomyoma-derived cell lines in vitro, repress the growth of these lines in nude mice, and, when administered over a 2- to 4-month course of treatment to Eker rats, reduce tumor incidence by more than 50%. In addition to endogenous hormones, xenoestrogens in our environment (e.g., phytoestrogens, organochlorine pesticides, pharmacologic compounds) are of potential concern with regards to their impact on this disease. These environmental estrogens have been shown to promote the growth of leiomyoma cells in vitro and in vivo. Further elucidation of the role of these and other hormonal and reproductive factors in the development of uterine leiomyoma will be invaluable for increasing our understanding of the etiology of this disease and developing new therapeutic strategies to help to reduce the negative impact of uterine leiomyomas on women's health.","PeriodicalId":21099,"journal":{"name":"Recent progress in hormone research","volume":"14 1","pages":"277-94"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86237976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular basis of mammalian gamete binding.","authors":"David J. Miller, Xudong Shi, H. Burkin","doi":"10.1210/RP.57.1.37","DOIUrl":"https://doi.org/10.1210/RP.57.1.37","url":null,"abstract":"Despite the importance of fertilization for controlling human reproduction, regulating animal production, and promoting preservation of endangered species, the molecular basis underlying gamete binding and fertilization has been perplexing. More progress has been made in the mouse than in other mammals and, recently, targeted deletion of specific genes in the mouse has yielded intriguing results. This review will emphasize research performed by our laboratory and others done primarily with mouse gametes but will include some interesting observations from other mammals. Studies of murine fertilization indicate that oligosaccharides on the egg coat glycoprotein ZP3 bind sperm. The precise oligosaccharides that bind sperm are the subject of considerable debate. ZP3 also induces exocytosis of the sperm acrosome, allowing sperm to penetrate through the egg coat (zona pellucida). A number of candidate ZP3 receptors have been proposed and studies of beta1,4galactosyltransferase-I (GalT-I) are reviewed here in the most detail. Sperm from mice with a targeted deletion of GalT-I still are able to bind the zona pellucida but are unable to acrosome react and penetrate through the zona. Therefore, the unique role of GalT-I appears to be in signal transduction. GalT-I forms a complex with heterotrimeric G proteins and activates signaling, leading to exocytosis in sperm and in heterologous cells expressing GalT-I. Other signaling steps triggered by GalT-I are under active investigation; this receptor forms a complex with a protein kinase anchoring protein. After exocytosis of the acrosome, sperm penetrate the zona pellucida and fuse with the oocyte plasma membrane using ADAM family members on sperm and integrins on oocytes. These proteins, along with the tetraspanins on oocytes, may form a complex web at gamete fusion. Targeted deletion of specific genes in this putative complex has provided important information about their redundancy. After the oocyte is fertilized, the binding site for GalT-I is lost from ZP3, preventing additional sperm from binding to the zona pellucida. New technical advances and creative ideas offer the opportunity to make important advances and to solve the conundrum of fertilization.","PeriodicalId":21099,"journal":{"name":"Recent progress in hormone research","volume":"13 1","pages":"37-73"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81642654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estrogen actions throughout the brain.","authors":"B. McEwen","doi":"10.1210/RP.57.1.357","DOIUrl":"https://doi.org/10.1210/RP.57.1.357","url":null,"abstract":"Besides affecting the hypothalamus and other brain areas related to reproduction, ovarian steroids have widespread effects throughout the brain, on serotonin pathways, catecholaminergic neurons, and the basal forebrain cholinergic system as well as the hippocampal formation, a brain region involved in spatial and declarative memory. Thus, ovarian steroids have measurable effects on affective state as well as cognition, with implications for dementia. Two actions are discussed in this review; both appear to involve a combination of genomic and nongenomic actions of ovarian hormones. First, regulation of the serotonergic system appears to be linked to the presence of estrogen- and progestin-sensitive neurons in the midbrain raphe as well as possibly nongenomic actions in brain areas to which serotonin neurons project their axons. Second, ovarian hormones regulate synapse turnover in the CA1 region of the hippocampus during the 4- to 5-day estrous cycle of the female rat. Formation of new excitatory synapses is induced by estradiol and involves N-methyl-D-aspartate (NMDA) receptors, whereas downregulation of these synapses involves intracellular progestin receptors. A new, rapid method of radioimmunocytochemistry has made possible the demonstration of synapse formation by labeling and quantifying the specific synaptic and dendritic molecules involved. Although NMDA receptor activation is required for synapse formation, inhibitory interneurons may play a pivotal role as they express nuclear estrogen receptor-alpha (ERa). It is also likely that estrogens may locally regulate events at the sites of synaptic contact in the excitatory pyramidal neurons where the synapses form. Indeed, recent ultrastructural data reveal extranuclear ERalpha immunoreactivity within select dendritic spines on hippocampal principal cells, axons, axon terminals, and glial processes. In particular, the presence of ER in dendrites is consistent with a model for synapse formation in which filopodia from dendrites grow out to find new synaptic contacts and estrogens regulate local, post-transcriptional events via second messenger systems.","PeriodicalId":21099,"journal":{"name":"Recent progress in hormone research","volume":"1 1","pages":"357-84"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72892450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular and molecular pathways regulating mammalian sex determination.","authors":"Christopher Tilmann, B. Capel","doi":"10.1210/RP.57.1.1","DOIUrl":"https://doi.org/10.1210/RP.57.1.1","url":null,"abstract":"In mammals, sex is determined by the presence or absence of a single gene on the Y chromosome, Sry. Sry, a member of the high mobility group family of transcription factors, is required to initiate male-specific pathways and repress female-specific pathways. Expression of Sry in the gonad, beginning at 10.5 days postcoitum, leads to the differentiation of the somatic supporting cell precursors as Sertoli cells. These cells direct the other cells of the gonad into their respective lineages. Currently, no direct targets of Sry are known. A number of cellular pathways initiated by Sry are required for testis development. These include the proliferation of pre-Sertoli cells and commitment to the Sertoli lineage, migration of cells from the adjacent mesonephros, and formation of a male-specific vasculature. Work is underway to identify genes controlling these processes. These genes will then be linked to Sry.","PeriodicalId":21099,"journal":{"name":"Recent progress in hormone research","volume":"23 1","pages":"1-18"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81034117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex steroids and bone.","authors":"S. Manolagas, S. Kousteni, R. Jilka","doi":"10.1210/RP.57.1.385","DOIUrl":"https://doi.org/10.1210/RP.57.1.385","url":null,"abstract":"The adult skeleton is periodically remodeled by temporary anatomic structures that comprise juxtaposed osteoclast and osteoblast teams and replace old bone with new. Estrogens and androgens slow the rate of bone remodeling and protect against bone loss. Conversely, loss of estrogen leads to increased rate of remodeling and tilts the balance between bone resorption and formation in favor of the former. Studies from our group during the last 10 years have elucidated that estrogens and androgens decrease the number of remodeling cycles by attenuating the birth rate of osteoclasts and osteoblasts from their respective progenitors. These effects result, in part, from the transcriptional regulation of genes responsible for osteoclastogenesis and mesenchymal cell replication and/or differentiation and are exerted through interactions of the ligand-activated receptors with other transcription factors. However, increased remodeling alone cannot explain why loss of sex steroids tilts the balance of resorption and formation in favor of the former. Estrogens and androgens also exert effects on the lifespan of mature bone cells: pro-apoptotic effects on osteoclasts but anti-apoptotic effects on osteoblasts and osteocytes. These latter effects stem from a heretofore unexpected function of the classical \"nuclear\" sex steroid receptors outside the nucleus and result from activation of a Src/Shc/extracellular signal-regulated kinase signal transduction pathway probably within preassembled scaffolds called caveolae. Strikingly, estrogen receptor (ER) alpha or beta or the androgen receptor can transmit anti-apoptotic signals with similar efficiency, irrespective of whether the ligand is an estrogen or an androgen. More importantly, these nongenotropic, sex-nonspecific actions are mediated by the ligand-binding domain of the receptor and can be functionally dissociated from transcriptional activity with synthetic ligands. Taken together, these lines of evidence strongly suggest that, in sex steroid deficiency, loss of transcriptional effects may be responsible for the increased osteoclastogenesis and osteoblastogenesis and thereby the increased rate of bone remodeling. Loss of nongenotropic anti-apoptotic effects on mature osteoblasts and osteocytes, in combination with an opposite effect on the lifespan of mature osteoclasts, may be responsible for the imbalance between formation and resorption and the progressive loss of bone mass and strength. Elucidation of the dual function of sex steroid receptors has important pathophysiologic and pharmacologic implications. Specifically, synthetic ligands of the ER that can evoke the nongenotropic but not the genotropic signal may be bone anabolic agents, as opposed to natural estrogens or selective estrogen receptor modulators that are antiresorptive agents. The same ligands may also circumvent the side effects associated with conventional hormone replacement therapy.","PeriodicalId":21099,"journal":{"name":"Recent progress in hormone research","volume":"51 1","pages":"385-409"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86649872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroendocrine modulation and repercussions of female reproductive aging.","authors":"P. Wise, Matthew J. Smith, D. Dubal, M. Wilson, S. Rau, Adrienne B. Cashion, M. Böttner, K. Rosewell","doi":"10.1210/RP.57.1.235","DOIUrl":"https://doi.org/10.1210/RP.57.1.235","url":null,"abstract":"The menopause marks the end of a woman's reproductive life. During the postmenopausal period, plasma estrogen concentrations decrease dramatically and remain low for the rest of her life, unless she chooses to take hormone replacement therapy. During the past 20 years, we have learned that changes in the central nervous system are associated with and may influence the timing of the menopause in women. Recently, it has become clear that estrogens act on more than just the hypothalamus, pituitary, ovary, and other reproductive organs. In fact, they play roles in a wide variety of nonreproductive functions. With the increasing life span of humans from approximately 50 to 80 years and the relatively fixed age of the menopause, a larger number of women will spend over one third of their lives in the postmenopausal state. It is not surprising that interest has increased in factors that govern the timing of the menopause and the repercussions of the lack of estrogen on multiple aspects of women's health. We have used animal models to better understand the complex interactions between the ovary and the brain that lead to the menopause and the repercussions of the hypoestrogenic state. Our results show that when rats reach middle age, the patterns and synchrony of multiple neurochemical events that are critical to the preovulatory gonadotropin-releasing hormone (GnRH) surge undergo subtle changes. The precision of rhythmic pattern of neurotransmitter dynamics depends on the presence of estradiol. Responsiveness to this hormone decreases in middle-aged rats. The lack of precision in the coordination in the output of neural signals leads to a delay and attenuation of the luteinizing hormone surge, which lead to irregular estrous cyclicity and, ultimately, to the cessation of reproductive cycles. We also have examined the impact of the lack of estrogen on the vulnerability of the brain to injury. Our work establishes that the absence of estradiol increases the extent of cell death after stroke-like injury and that treatment with low physiological levels of estradiol are profoundly neuroprotective. We have begun to explore the cellular and molecular mechanisms that underlie this novel nonreproductive action of estrogens. In summary, our studies show that age-related changes in the ability of estradiol to coordinate the neuroendocrine events that lead to regular preovulatory GnRH surges contribute to the onset of irregular estrous cycles and eventually to acyclicity. Furthermore, we have shown that the lack of estradiol increases the vulnerability of the brain to injury and neurodegeneration.","PeriodicalId":21099,"journal":{"name":"Recent progress in hormone research","volume":"57 1","pages":"235-56"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84881124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Steroidogenic factor 1: an essential mediator of endocrine development.","authors":"K. Parker, D. Rice, D. Lala, Y. Ikeda, Xunrong Luo, M. Wong, M. Bakke, Liping Zhao, C. Frigeri, N. Hanley, N. Stallings, B. Schimmer","doi":"10.1210/RP.57.1.19","DOIUrl":"https://doi.org/10.1210/RP.57.1.19","url":null,"abstract":"The orphan nuclear receptor steroidogenic factor 1 (SF-1, also called Ad4BP and officially designated NR5A1) has emerged as an essential regulator of endocrine development and function. Initially identified as a tissue-specific transcriptional regulator of the cytochrome P450 steroid hydroxylases, SF-1 has considerably broader roles, as evidenced from studies in knockout mice lacking SF-1. The SF-1-knockout mice lacked adrenal glands and gonads and therefore died from adrenal insufficiency within the first week after birth. In addition, SF-1 knockout mice exhibited male-to-female sex reversal of their internal and external genitalia, impaired expression of multiple markers of pituitary gonadotropes, and agenesis of the ventromedial hypothalamic nucleus (VMH). These studies delineated essential roles of SF-I in regulating endocrine differentiation and function at multiple levels, particularly with respect to reproduction. This chapter will review the experiments that established SF-1 as a pivotal, global determinant of endocrine differentiation and function. We next discuss recent insights into the mechanisms controlling the expression and function of SF-1 as well as the current status of research aimed at delineating its roles in specific tissues. Finally, we highlight areas where additional studies are needed to expand our understanding of SF-1 action.","PeriodicalId":21099,"journal":{"name":"Recent progress in hormone research","volume":"229 1","pages":"19-36"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90684677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}