GnRH pulse frequency is decoded by distinct Gα_s- and Gα_q/11-mediated signaling pathways in gonadotropes in vitro.

Authors

George A Stamatiades, Iain R Thompson, Han Kyeol Kim, Rona S Carroll, Ursula B Kaiser

Published in

Hormones (Athens, Greece). Jul 30, 2026. Epub Jul 30, 2026.

Abstract

Pulsatile gonadotropin-releasing hormone (GnRH) secretion differentially regulates follicle-stimulating hormone β-subunit (Fshb) expression according to pulse frequency; however, the mechanisms by which pituitary gonadotropes decode GnRH pulsatility remain incompletely understood. GnRH activates both Gα_s- and Gα_q/11-mediated signaling pathways, and the transcriptional regulators cAMP response element-binding protein (Creb) and inducible cAMP early repressor (Icer) have been implicated in Fshb regulation. This study examined whether distinct G protein-dependent pathways regulate Creb and Icer in a GnRH pulse frequency-dependent manner.
Murine gonadotrope-derived LβT2 cells were transduced with lentiviral shRNA targeting Gnas (Gα_s), Gnaq/Gna11 (Gα_q/11), or scrambled controls. Cells were perifused and stimulated with pulsatile GnRH (10 nM) at low (every 120 min) or high (every 30 min) pulse frequencies for 20 h. Creb and Erk1/2 phosphorylation were assessed by immunoblotting and Icer and Egr1 mRNA levels were measured by real-time PCR.
GnRH induced pulse frequency-dependent signaling, with enhanced Creb phosphorylation at low pulse frequency and preferential Icer induction at high frequency. Gnas knockdown selectively attenuated Creb phosphorylation at low pulse frequency without affecting Icer expression. In contrast, Gnaq/Gna11 knockdown reduced Icer induction at high pulse frequency and markedly attenuated Erk1/2 phosphorylation and Egr1 expression at both frequencies.
GnRH pulse frequency is decoded in gonadotropes through differential engagement of G protein-dependent signaling pathways. Gα_s-mediated signaling pathways preferentially activate Creb at low pulse frequencies, whereas Gα_q/11-mediated pathways promote Erk-dependent Icer and Egr1 induction at higher pulse frequencies, providing a mechanism for differential regulation of FSH and LH synthesis.

PMID:
42533270
Bibliographic data and abstract were imported from PubMed on 31 Jul 2026.

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