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  Deletion of G alpha(q/11) or G alpha(s) Proteins in Gonadotropes Differentially Affects Gonadotropin Production and Secretion in Mice

Stamatiades, G. A., Toufaily, C., Kim, H. K., Zhou, X., Thompson, I. R., Carroll, R. S., et al. (2022). Deletion of G alpha(q/11) or G alpha(s) Proteins in Gonadotropes Differentially Affects Gonadotropin Production and Secretion in Mice. ENDOCRINOLOGY, 163(2): bqab247. doi:10.1210/endocr/bqab247.

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 Creators:
Stamatiades, George A., Author
Toufaily, Chirine, Author
Kim, Han Kyeol, Author
Zhou, Xiang, Author
Thompson, Iain R., Author
Carroll, Rona S., Author
Chen, Min, Author
Weinstein, Lee S., Author
Offermanns, Stefan1, Author              
Boehm, Ulrich, Author
Bernard, Daniel J., Author
Kaiser, Ursula B., Author
Affiliations:
1Pharmacology, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591696              

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 Abstract: Gonadotropin-releasing hormone (GnRH) regulates gonadal function via its stimulatory effects on gonadotropin production by pituitary gonadotrope cells. GnRH is released from the hypothalamus in pulses and GnRH pulse frequency differentially regulates follicle-stimulating hormone (FSH) and luteinizing hormone (LH) synthesis and secretion. The GnRH receptor (GnRHR) is a G protein-coupled receptor that canonically activates G alpha (q/11)-dependent signaling on ligand binding. However, the receptor can also couple to G alpha (s) and in vitro data suggest that toggling between different G proteins may contribute to GnRH pulse frequency decoding. For example, as we show here, knockdown of G alpha (s) impairs GnRH-stimulated FSH synthesis at low- but not high-pulse frequency in a model gonadotrope-derived cell line. We next used a Cre-lox conditional knockout approach to interrogate the relative roles of G alpha (q/11) and G alpha (s) proteins in gonadotrope function in mice. Gonadotrope-specific G alpha (q/11) knockouts exhibit hypogonadotropic hypogonadism and infertility, akin to the phenotypes seen in GnRH- or GnRHR-deficient mice. In contrast, under standard conditions, gonadotrope-specific G alpha (s) knockouts produce gonadotropins at normal levels and are fertile. However, the LH surge amplitude is blunted in G alpha (s) knockout females and postgonadectomy increases in FSH and LH are reduced both in males and females. These data suggest that GnRH may signal principally via G alpha (q/11) to stimulate gonadotropin production, but that G alpha (s) plays important roles in gonadotrope function in vivo when GnRH secretion is enhanced.

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 Dates: 2021-12-052022-02
 Publication Status: Published in print
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 Rev. Type: -
 Identifiers: ISI: 000753587100019
DOI: 10.1210/endocr/bqab247
PMID: 34864945
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Title: ENDOCRINOLOGY
Source Genre: Journal
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Pages: - Volume / Issue: 163 (2) Sequence Number: bqab247 Start / End Page: - Identifier: ISSN: 0013-7227