| First Author | Stamatiades GA | Year | 2022 |
| Journal | Endocrinology | Volume | 163 |
| Issue | 2 | PubMed ID | 34864945 |
| Mgi Jnum | J:324595 | Mgi Id | MGI:7277753 |
| Doi | 10.1210/endocr/bqab247 | Citation | Stamatiades GA, et al. (2022) Deletion of Galphaq/11 or Galphas Proteins in Gonadotropes Differentially Affects Gonadotropin Production and Secretion in Mice. Endocrinology 163(2) |
| abstractText | 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 Galpha q/11-dependent signaling on ligand binding. However, the receptor can also couple to Galpha 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 Galpha 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 Galpha q/11 and Galpha s proteins in gonadotrope function in mice. Gonadotrope-specific Galpha 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 Galpha s knockouts produce gonadotropins at normal levels and are fertile. However, the LH surge amplitude is blunted in Galpha 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 Galpha q/11 to stimulate gonadotropin production, but that Galpha s plays important roles in gonadotrope function in vivo when GnRH secretion is enhanced. |
