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FSH-deficiency in gonadotrope-specific GATA2 knockout mice is associated with a loss of gremlin expression

ABSTRACT: FSH-deficiency in gonadotrope-specific GATA2 knockout mice is associated with a loss of gremlin expression

PROVIDER: PRJNA785651 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17106100_1.fastq.gz	Fastqsanger.gz
	SRR17106100_2.fastq.gz	Fastqsanger.gz
	SRR17106101_1.fastq.gz	Fastqsanger.gz
	SRR17106101_2.fastq.gz	Fastqsanger.gz
	SRR17106102_1.fastq.gz	Fastqsanger.gz

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FSH-deficiency in gonadotrope-specific GATA2 knockout mice is associated with a loss of gremlin expression [snATAC-Seq]

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