Intra-pituitary follicle-stimulating hormone signaling regulates hepatic lipid metabolism
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE216096 | GEO | 2023/01/11
REPOSITORIES: GEO
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Project description:Gonadotropin-releasing hormone (GnRH) governs reproduction in vertebrates by regulating pituitary gonadotropins. Zebrafish, however, is an exception as gnrh3–/– fish, which lack the hypophysiotropic GnRH3, are fertile, suggesting that zebrafish utilizes a Gnrh-independent mechanism to regulate reproduction. To elucidate the role of Gnrh3 and the Gnrh-independent mechanisms that regulate the pituitary gonadotropes, we profiled the gene expression in individual pituitary cells of wild-type and gnrh–/– adult female zebrafish and identified transcriptionally defined cell types. The classical Lh and Fsh gonadotropes expressed both gonadotropin beta subunits with a ratio of 13:1 (lhb:fshb) and 40:1 (fshb:lhb), respectively. We discovered that Lh gonadotropes predominantly express genes encoding receptors for Gnrh (gnrhr2), thyroid hormone, estrogen, dopamine, and steroidogenic factor 1 (SF1). No Gnrh receptor expression was enriched in Fsh gonadotropes, instead, the expression of cholecystokinin receptor (cckrb) and galanin receptor (gal1rb) were enriched in these cells. The hereditary loss of Gnrh3 gene resulted in downregulation of fshb in Lh gonadotropes. Likewise, targeted chemogenetic ablation of Gnrh3 neurons led to a decrease in the number of fshb+/lhb+ cells. Our studies suggest that Gnrh3 directly acts on Lh gonadotropes through Gnrhr2, but the outcome of this interaction is still unknown. Gnrh3 also regulates fshb expression, probably via a non-Gnrh receptor route. Altogether, while Lh secretion and synthesis are likely regulated by multiple factors in a Gnrh-independent manner, Gnrh3 seems to play a role in the cellular organization of the pituitary in zebrafish.
2024-11-20 | GSE272806 | GEO
Project description:Mammalian reproduction is dependent on the gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone, which are secreted by pituitary gonadotrope cells. The zinc-finger transcription factor, GATA2, was previously implicated in FSH production in male mice, although its mechanisms of action and role in females were not determined. To address these gaps in knowledge, we generated and analyzed gonadotrope-specific Gata2 knockout mice using the Cre-lox system. While conditional knockout (cKO) males exhibited ~50% reductions in serum FSH levels and pituitary FSHβ subunit (Fshb) expression relative to controls, FSH production was apparently normal in cKO females. RNA-seq analysis of purified gonadotropes from control and cKO males revealed a profound decrease in expression of gremlin (Grem1), a bone morphogenetic protein (BMP) antagonist. Grem1 was expressed in gonadotropes, but not other cell lineages, in the adult male mouse pituitary. Gata2, Grem1, and Fshb mRNA levels were significantly higher in pituitaries of wild-type males relative to females but decreased in males treated with estradiol and increased following ovariectomy in control but not cKO females. Recombinant gremlin stimulated Fshb expression in pituitary cultures from wild-type mice. Collectively, the data suggest that GATA2 promotes Grem1 expression in gonadotropes and that the gremlin protein potentiates FSH production. The mechanisms of gremlin action have not yet been established but may involve attenuation of BMP binding to activin type II receptors in gonadotropes, potentiating induction of Fshb transcription by activins or related ligands.
2022-07-14 | GSE190060 | GEO
Project description:Mammalian reproduction is dependent on the gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone, which are secreted by pituitary gonadotrope cells. The zinc-finger transcription factor, GATA2, was previously implicated in FSH production in male mice, although its mechanisms of action and role in females were not determined. To address these gaps in knowledge, we generated and analyzed gonadotrope-specific Gata2 knockout mice using the Cre-lox system. While conditional knockout (cKO) males exhibited ~50% reductions in serum FSH levels and pituitary FSHβ subunit (Fshb) expression relative to controls, FSH production was apparently normal in cKO females. RNA-seq analysis of purified gonadotropes from control and cKO males revealed a profound decrease in expression of gremlin (Grem1), a bone morphogenetic protein (BMP) antagonist. Grem1 was expressed in gonadotropes, but not other cell lineages, in the adult male mouse pituitary. Gata2, Grem1, and Fshb mRNA levels were significantly higher in pituitaries of wild-type males relative to females but decreased in males treated with estradiol and increased following ovariectomy in control but not cKO females. Recombinant gremlin stimulated Fshb expression in pituitary cultures from wild-type mice. Collectively, the data suggest that GATA2 promotes Grem1 expression in gonadotropes and that the gremlin protein potentiates FSH production. The mechanisms of gremlin action have not yet been established but may involve attenuation of BMP binding to activin type II receptors in gonadotropes, potentiating induction of Fshb transcription by activins or related ligands.
2022-07-14 | GSE189915 | GEO
Project description:Mammalian reproduction is dependent on the gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone, which are secreted by pituitary gonadotrope cells. The zinc-finger transcription factor, GATA2, was previously implicated in FSH production in male mice, although its mechanisms of action and role in females were not determined. To address these gaps in knowledge, we generated and analyzed gonadotrope-specific Gata2 knockout mice using the Cre-lox system. While conditional knockout (cKO) males exhibited ~50% reductions in serum FSH levels and pituitary FSHβ subunit (Fshb) expression relative to controls, FSH production was apparently normal in cKO females. RNA-seq analysis of purified gonadotropes from control and cKO males revealed a profound decrease in expression of gremlin (Grem1), a bone morphogenetic protein (BMP) antagonist. Grem1 was expressed in gonadotropes, but not other cell lineages, in the adult male mouse pituitary. Gata2, Grem1, and Fshb mRNA levels were significantly higher in pituitaries of wild-type males relative to females but decreased in males treated with estradiol and increased following ovariectomy in control but not cKO females. Recombinant gremlin stimulated Fshb expression in pituitary cultures from wild-type mice. Collectively, the data suggest that GATA2 promotes Grem1 expression in gonadotropes and that the gremlin protein potentiates FSH production. The mechanisms of gremlin action have not yet been established but may involve attenuation of BMP binding to activin type II receptors in gonadotropes, potentiating induction of Fshb transcription by activins or related ligands.
2022-07-14 | GSE190064 | GEO
Project description:From mammals to fish, gametogenesis and sexual maturation are driven by luteinizing hormone (LH) and follicle-stimulating hormone (FSH), the gonadotropic hormones temporally secreted from the pituitary. Teleost fish are an excellent model for addressing the unique regulation and function of each gonadotropin cell because, unlike mammals, they synthesize and secrete LH and FSH from distinct cells. Only two very distant vertebrate classes (fish and birds), demonstrate the mono-hormonal strategy suggesting a potential convergent evolution. By performing cell specific transcriptome analysis of double-labelled transgenic Nile tilapia (Oreochromis niloticus) expressing GFP and RFP in LH or FSH cells, respectively, we identified genes specifically enriched in each cell type, revealing differences in hormone regulation, receptors expression, cell signaling, and electrical properties. We found that each LH and FSH cell in fish express unique GPCR signature that reveals the direct regulation of metabolic and homeostatic hormones. Comparing these novel transcriptomes to that of rat gonadotrophs revealed conserved genes that might specifically contribute to each gonadotropin activity in mammals, suggesting conserved mechanisms controlling the differential regulation of gonadotropins in vertebrates.
2020-10-14 | GSE159470 | GEO
Project description:Background: Circulating miRNAs in pituitary adenoma would help patient care especially in non-functioning adenoma cases as minimally invasive biomarkers of tumor recurrence and progression. Aim: Our aim was to investigate plasma miRNA profile in patients with pituitary adenoma. Materials and Methods: 149 plasma and extracellular vesicle (preoperative, early- and late postoperative) samples were collected from 45 pituitary adenoma patients. Adenomas were characterized based on anterior pituitary hormones and transcription factors by immunostaining. MiRNA next generation sequencing was performed on 36 samples (discovery set). Individual TaqMan assay was used for validation on extended sample set. PA tissue miRNAs were evaluated by TaqMan array and literature data. Results: Global downregulation of miRNA expression was observed in plasma samples of pituitary adenoma patients compared to normal samples. Expression of 29 miRNAs and isomiR variants were able to distinguish preoperative plasma samples and normal controls. MiRNAs with altered expression in both plasma and different adenoma tissues were identified. 3, 7 and 66 miRNAs expressed differentially between preoperative and postoperative plasma samples in growth hormone secreting, FSH/LH+ and hormone-immunonegative groups, respectively. MiR-143-3p was downregulated in late- but not in early postoperative plasma samples compared to preoperative ones exclusively in FSH/LH+ adenomas. Plasma level of miR-143-3p discriminated these samples with 81.8% sensitivity and 72.3% specificity (AUC=0.79; p=0.02). Conclusions: Differentially expressed miRNAs in pituitary adenoma tissues have low abundance in plasma minimizing their role as biomarkers. Plasma miR-143-3p decreases in patients with FSH/LH+ adenoma indicated successful surgery, but its application for evaluating tumor recurrence needs further investigation.
2019-05-21 | GSE131483 | GEO
Project description:In the normal mouse the pituitary gonadotrophins determine development, maturation and physiological regulation of the testis with follicle-stimulating hormone (FSH) activating the Sertoli cell and luteinising hormone (LH) the Leydig cell. To look at the potential interaction of cell types within the testis following hormone stimulation we have investigated the effect of rFSH on testicular gene expression in the hypogonadal (hpg) male mouse. Due to a deletion in the gene encoding gonadotrophin-releasing hormone (GnRH), FSH and LH levels are at the lower limit of detection in the circulation and mice remain in a pre-pubertal state throughout life unless given exogenous hormone. Here we have addressed important question of changes in the global gene expression profile of testicular tissue following hormone stimulation (rFSH) for 12, 24 and 72h following injections compared to control untreated hpg males of the same age. Keywords: Hormone Response, Testicular gene expression Profile
2009-08-18 | GSE8924 | GEO
Project description:The inhibins control reproduction by suppressing follicle-stimulating hormone synthesis by pituitary gonadotrope cells. The recently discovered inhibin B co-receptor mediating this inhibition, TGFBR3L, is selectively and highly expressed in gonadotropes in both mice and humans. We sought to characterize mechanisms controlling cell-specific Tgfbr3l/TGFBR3L transcription. We identified two steroidogenic factor 1 (SF-1) cis-elements in the proximal Tgfbr3l promoter in mice. Using single-nucleus ATAC-seq we find that gonadotrope-specific SF-1 (Nr5a1) knockout mice, which exhibit hypogonadotropic hypogonadism, display, contrary to controls, closed chromatin in the promoter region of theTgfbr3l gene in gonadotropes. These, and other, data collectively indicate that SF-1 directly regulates Tgfbr3l/TGFBR3L transcription, contributing to gonadotrope-specific expression of the gene.
2023-03-13 | GSE198907 | GEO
Project description:Follicle-stimulating hormone (FSH), a dimeric glycoprotein produced by pituitary gonadotrope cells, regulates spermatogenesis in males and ovarian follicle growth in females. Hypothalamic gonadotropin-releasing hormone (GnRH) stimulates FSHβ subunit gene (Fshb) transcription, though the underlying mechanisms are poorly understood. To address this gap in knowledge, we examined changes in pituitary gene expression in GnRH-deficient mice (hpg) treated with a regimen of exogenous GnRH that increases pituitary Fshb but not luteinizing hormone β (Lhb) mRNA levels. Activating transcription factor 3 (Atf3) was among the most upregulated genes. ATF3 can heterodimerize with members of the AP-1 family to regulate gene transcription. Co-expression of ATF3 with JunB stimulated murine Fshb, but not Lhb, promoter-reporter activity in homologous LβT2 cells. ATF3 also synergized with a constitutively active activin type I receptor to increase endogenous Fshb expression in these cells. Nevertheless, FSH production was intact in gonadotrope-specific Atf3 knockout mice (cKO) and control littermates. Ovarian follicle development, ovulation, and litter sizes were also equivalent between genotypes. Testis weights and sperm counts did not differ between cKO and control males. Following gonadectomy, increases in LH secretion were enhanced in cKO animals. Though FSH levels did not differ between genotypes, post-gonadectomy increases in pituitary Fshb and gonadotropin α subunit expression were more pronounced in cKO mice. These data indicate that ATF3 can selectively stimulate Fshb transcription in vitro but is not required for FSH production in vivo.
2023-06-28 | GSE220809 | GEO
Project description:In all vertebrates, the dual function of testis (production of sexual steroids and production of gametes) is mainly regulated by two gonadotropic pituitary hormones, FSH and LH. However, in fish the biological activities of the two hormones are not still clearly delineated and moreover, their molecular mechanisms are yet poorly understood. In this study we investigated the effects of FSH and LH on testicular gene expression, in the rainbow trout, at two developmental stages I-II and III (I: spermatogonia only, II: active spermatogonia proliferation, III: meiosis onset with the appearance of spermatocytes and round spermatids). Testes were collected from all-male population rainbow trout and incubated in six replicates for 96 hours, at 12°C, in the absence or presence of purified salmonid gonadotropins, FSH and LH (500 ng/mL).
2012-10-22 | E-GEOD-39465 | biostudies-arrayexpress