Activating Transcription Factor 3 Stimulates Follicle-Stimulating Hormone-β Expression In Vitro But Is Dispensable for Follicle-Stimulating Hormone Production in Murine Gonadotropes In Vivo.
GnRH
cell line
knockout mouse
pituitary
transcription
Journal
Endocrinology
ISSN: 1945-7170
Titre abrégé: Endocrinology
Pays: United States
ID NLM: 0375040
Informations de publication
Date de publication:
13 03 2023
13 03 2023
Historique:
received:
06
01
2023
pmc-release:
23
03
2024
medline:
7
4
2023
pubmed:
24
3
2023
entrez:
23
3
2023
Statut:
ppublish
Résumé
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) messenger RNA levels. Activating transcription factor 3 (Atf3) was among the most upregulated genes. Activating transcription factor 3 (ATF3) can heterodimerize with members of the activator protein 1 family to regulate gene transcription. Co-expression of ATF3 with JunB stimulated murine Fshb, but not Lhb, promoter-reporter activity in homologous LβT2b 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 [conditional knockout (cKO)] mice. Ovarian follicle development, ovulation, and litter sizes were equivalent between cKOs and controls. Testis weights and sperm counts did not differ between genotypes. 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 than control mice. These data indicate that ATF3 can selectively stimulate Fshb expression in vitro but is not required for FSH production in vivo.
Identifiants
pubmed: 36951304
pii: 7084717
doi: 10.1210/endocr/bqad050
pmc: PMC10282924
pii:
doi:
Substances chimiques
Follicle Stimulating Hormone
9002-68-0
Activating Transcription Factor 3
0
Gonadotropins
0
Gonadotropin-Releasing Hormone
33515-09-2
Follicle Stimulating Hormone, beta Subunit
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK046943
Pays : United States
Informations de copyright
© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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