G Proteins and Autocrine Signaling Differentially Regulate Gonadotropin Subunit Expression in Pituitary Gonadotrope

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2012 May 3

PMID 22549790

Citations 20

Authors

Soon-Gang Choi

Jingjing Jia

Robert L Pfeffer

Stuart C Sealfon

Affiliations

Soon will be listed here.

Abstract

Gonadotropin-releasing hormone (GnRH) acts at gonadotropes to direct the synthesis of the gonadotropins, follicle-stimulating hormone (FSH), and luteinizing hormone (LH). The frequency of GnRH pulses determines the pattern of gonadotropin synthesis. Several hypotheses for how the gonadotrope decodes GnRH frequency to regulate gonadotropin subunit genes differentially have been proposed. However, key regulators and underlying mechanisms remain uncertain. We investigated the role of individual G proteins by perturbations using siRNA or bacterial toxins. In LβT2 gonadotrope cells, FSHβ gene induction depended predominantly on Gα(q/11), whereas LHβ expression depended on Gα(s). Specifically reducing Gα(s) signaling also disinhibited FSHβ expression, suggesting the presence of a Gα(s)-dependent signal that suppressed FSH biosynthesis. The presence of secreted factors influencing FSHβ expression levels was tested by studying the effects of conditioned media from Gα(s) knockdown and cholera toxin-treated cells on FSHβ expression. These studies and related Transwell culture experiments implicate Gα(s)-dependent secreted factors in regulating both FSHβ and LHβ gene expression. siRNA studies identify inhibinα as a Gα(s)-dependent GnRH-induced autocrine regulatory factor that contributes to feedback suppression of FSHβ expression. These results uncover differential regulation of the gonadotropin genes by Gα(q/11) and by Gα(s) and implicate autocrine and gonadotrope-gonadotrope paracrine regulatory loops in the differential induction of gonadotropin genes.

Citing Articles

Deletion of Gαq/11 or Gαs Proteins in Gonadotropes Differentially Affects Gonadotropin Production and Secretion in Mice.

Stamatiades G, Toufaily C, Kim H, Zhou X, Thompson I, Carroll R Endocrinology. 2021; 163(2).

PMID: 34864945 PMC: 8711759. DOI: 10.1210/endocr/bqab247.

Actions and Roles of FSH in Germinative Cells.

Recchia K, Jorge A, Pessoa L, Botigelli R, Zugaib V, de Souza A Int J Mol Sci. 2021; 22(18).

PMID: 34576272 PMC: 8470522. DOI: 10.3390/ijms221810110.

Advances in the Regulation of Mammalian Follicle-Stimulating Hormone Secretion.

Wang H, Zhang W, Yuan B, Zhang J Animals (Basel). 2021; 11(4).

PMID: 33921032 PMC: 8071398. DOI: 10.3390/ani11041134.

SRXN1 Is Necessary for Resolution of GnRH-Induced Oxidative Stress and Induction of Gonadotropin Gene Expression.

Kim T, Li D, Terasaka T, Nicholas D, Knight V, Yang J Endocrinology. 2019; 160(11):2543-2555.

PMID: 31504396 PMC: 6779075. DOI: 10.1210/en.2019-00283.

Cytogenetic, Genomic, and Functional Characterization of Pituitary Gonadotrope Cell Lines.

Ruf-Zamojski F, Ge Y, Pincas H, Shan J, Song Y, Hines N J Endocr Soc. 2019; 3(5):902-920.

PMID: 31020055 PMC: 6469952. DOI: 10.1210/js.2019-00064.

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