Topic
FSHB
About: FSHB is a research topic. Over the lifetime, 334 publications have been published within this topic receiving 9675 citations. The topic is also known as: HH24 & follicle stimulating hormone beta subunit.
Papers published on a yearly basis
Papers
TL;DR: To generate animal models for human diseases involving the gonadotropin signal transduction pathway, mice deficient in the FSHβ subunit are produced and therefore in FSH using ES cell technology.
Abstract: Follicle stimulating hormone (FSH) is a member of the glycoprotein hormone family that includes luteinzing hormone (LH), thyroid stimulating hormone, and chorionic gonadotropin. These heterodimeric hormones share a common alpha subunit and differ in their hormone-specific beta subunit. The biological activity is conferred only by the heterodimers. FSH and LH are synthesized in the same cells of the pituitary, the gonadotrophs. FSH receptors are localized to Sertoli cells of the testes and granulosa cells of the ovary. Minimal data has been accumulated so far involving human mutations in the FSH beta, LH beta, or the gonadotropin receptor genes. There are no known mouse strains with mutations in the FSH beta gene. To generate animal models for human diseases involving the gonadotropin signal transduction pathway, we produced mice deficient in the FSH beta subunit and therefore in FSH using ES cell technology. FSH-deficient females are infertile due to a block in folliculogenesis prior to antral follicle formation. Although FSH was predicted to be necessary for spermatogenesis and Sertoli cell growth in males, FSH-deficient males are fertile despite having small testes. Our findings have important implications for male contraceptive development in humans.
1,369 citations
Northwestern University1, University of Chicago2, University of Oxford3, University of Warwick4, Hammersmith Hospital5, Broad Institute6, University of Utah7, National and Kapodistrian University of Athens8, Aristotle University of Thessaloniki9, Cedars-Sinai Medical Center10, Georgia Regents University11, Medical College of Wisconsin12, Texas Biomedical Research Institute13, Karolinska Institutet14, Pennsylvania State University15, University of Colorado Denver16, Duke University17, Stanford University18, University of Pennsylvania19, University of Alabama20, University of Texas Health Science Center at San Antonio21, University of Texas Southwestern Medical Center22, Baylor College of Medicine23, University of Vermont24, University of Michigan25, Wayne State University26, National Institutes of Health27, University of Pittsburgh28, University of California, San Francisco29, University of Virginia30, Yale University31, Virginia Commonwealth University32, Rutgers University33, State University of New York Upstate Medical University34, Carolinas Medical Center35
TL;DR: Common genetic susceptibility loci in European ancestry women for the National Institutes of Health PCOS phenotype are identified, which confers the highest risk for metabolic morbidities, as well as reproductive hormone levels, and implicate neuroendocrine changes in disease pathogenesis.
Abstract: Polycystic ovary syndrome (PCOS) is a common, highly heritable complex disorder of unknown aetiology characterized by hyperandrogenism, chronic anovulation and defects in glucose homeostasis. Increased luteinizing hormone relative to follicle-stimulating hormone secretion, insulin resistance and developmental exposure to androgens are hypothesized to play a causal role in PCOS. Here we map common genetic susceptibility loci in European ancestry women for the National Institutes of Health PCOS phenotype, which confers the highest risk for metabolic morbidities, as well as reproductive hormone levels. Three loci reach genome-wide significance in the case–control meta-analysis, two novel loci mapping to chr 8p32.1 and chr 11p14.1, and a chr 9q22.32 locus previously found in Chinese PCOS. The same chr 11p14.1 SNP, rs11031006, in the region of the follicle-stimulating hormone B polypeptide (FSHB) gene strongly associates with PCOS diagnosis and luteinizing hormone levels. These findings implicate neuroendocrine changes in disease pathogenesis.
506 citations
TL;DR: Overall, these findings indicate that ERalpha, but not ERbeta, is indispensable to the negative-feedback effects of estradiol that maintain proper LH secretion from the pituitary.
Abstract: To determine the role of each estrogen receptor (ER) form (ERalpha, ERbeta) in mediating the estrogen actions necessary to maintain proper function of the hypothalamic-pituitary-gonadal axis, we have characterized the hypothalamic-pituitary-gonadal axis in female ER knockout (ERKO) mice. Evaluation of pituitary function included gene expression assays for Gnrhr, Cga, Lhb, Fshb, and Prl. Evaluation of ovarian steroidogenic capacity included gene expression assays for the components necessary for estradiol synthesis: i.e. Star, Cyp11a, Cyp17, Cyp19, Hsd3b1, and Hsd17b1. These data were corroborated by assessing plasma levels of the respective peptide and steroid hormones. alphaERKO and alphabetaERKO females exhibited increased pituitary Cga and Lhb expression and increased plasma LH levels, whereas both were normal in betaERKO. Pituitary Fshb expression and plasma FSH were normal in all three ERKOs. In the ovary, all three ERKOs exhibited normal expression of Star, Cyp11a, and Hsd3b1. In contrast, Cyp17 and Cyp19 expression were elevated in alphaERKO but normal in betaERKO and alphabetaERKO. Plasma steroid levels in each ERKO mirrored the steroidogenic enzyme expression, with only the alphaERKO exhibiting elevated androstenedione and estradiol. Elevated plasma testosterone in alphaERKO and alphabetaERKO females was attributable to aberrant expression of Hsd17b3 in the ovary, representing a form of endocrine sex reversal, as this enzyme is unique to the testes. Enhanced steroidogenic capacity in alphaERKO ovaries was erased by treatment with a GnRH antagonist, indicating these phenotypes to be the indirect result of excess LH stimulation that follows the loss of ERalpha in the hypothalamic-pituitary axis. Overall, these findings indicate that ERalpha, but not ERbeta, is indispensable to the negative-feedback effects of estradiol that maintain proper LH secretion from the pituitary. The subsequent hypergonadism is illustrated as increased Cyp17, Cyp19, Hsd17b1, and ectopic Hsd17b3 expression in the ovary.
323 citations
QIMR Berghofer Medical Research Institute1, St. Jude Children's Research Hospital2, deCODE genetics3, University of Liverpool4, Wellcome Trust Centre for Human Genetics5, Katholieke Universiteit Leuven6, Brigham and Women's Hospital7, Harvard University8, University of Queensland9, Vanderbilt University Medical Center10, Copenhagen University Hospital11, University of California, San Diego12, John Radcliffe Hospital13, Niigata University14, University of Tokyo15, RMIT University16, Lundbeck17, Aarhus University18, Merck KGaA19, Queensland University of Technology20
TL;DR: A meta-analysis of genome-wide association case-control data sets for endometriosis highlights novel variants in or near specific genes with important roles in sex steroid hormone signalling and function, and offers unique opportunities for more targeted functional research efforts.
Abstract: Endometriosis is a heritable hormone-dependent gynecological disorder, associated with severe pelvic pain and reduced fertility; however, its molecular mechanisms remain largely unknown Here we perform a meta-analysis of 11 genome-wide association case-control data sets, totalling 17,045 endometriosis cases and 191,596 controls In addition to replicating previously reported loci, we identify five novel loci significantly associated with endometriosis risk (P<5 × 10-8), implicating genes involved in sex steroid hormone pathways (FN1, CCDC170, ESR1, SYNE1 and FSHB) Conditional analysis identified five secondary association signals, including two at the ESR1 locus, resulting in 19 independent single nucleotide polymorphisms (SNPs) robustly associated with endometriosis, which together explain up to 519% of variance in endometriosis These results highlight novel variants in or near specific genes with important roles in sex steroid hormone signalling and function, and offer unique opportunities for more targeted functional research efforts
300 citations
TL;DR: It is demonstrated for the first time that adult male exposure to BPA caused a reduction in sperm production and specific functional parameters, and the corresponding pattern of gene expression is indicative of an attempt by the pituitary to reestablish normal levels of LH, FSH and testosterone serum concentrations.
239 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2021 | 17 |
| 2020 | 31 |
| 2019 | 22 |
| 2018 | 15 |
| 2017 | 31 |
| 2016 | 20 |