Role of L-glutamine in the regulation of rat Sertoli cell proliferation by FSH

in Reproduction
Authors:
Cecilia Lucia Centola Centro de Investigaciones Endocrinológicas “Dr. César Bergadá” (CEDIE) CONICET - FEI - División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Gallo 1330, Ciudad Autónoma de Buenos Aires, Argentina

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Marina Ercilia Dasso Centro de Investigaciones Endocrinológicas “Dr. César Bergadá” (CEDIE) CONICET - FEI - División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Gallo 1330, Ciudad Autónoma de Buenos Aires, Argentina

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Maria Fernanda Riera Centro de Investigaciones Endocrinológicas “Dr. César Bergadá” (CEDIE) CONICET - FEI - División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Gallo 1330, Ciudad Autónoma de Buenos Aires, Argentina

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Silvina Beatriz Meroni Centro de Investigaciones Endocrinológicas “Dr. César Bergadá” (CEDIE) CONICET - FEI - División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Gallo 1330, Ciudad Autónoma de Buenos Aires, Argentina

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Maria Noel Galardo Centro de Investigaciones Endocrinológicas “Dr. César Bergadá” (CEDIE) CONICET - FEI - División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Gallo 1330, Ciudad Autónoma de Buenos Aires, Argentina

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https://orcid.org/0000-0002-2678-622X

Correspondence should be addressed to M N Galardo: mngalardo@cedie.org.ar
DOI:
https://doi.org/10.1530/REP-24-0177
Volume/Issue:
Volume 168: Issue 5
Article ID:
e240177
Article Type:
Research Article
Online Publication Date:
21 Sep 2024
Copyright:
© the author(s) 2024
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In brief

FSH leads to glutamine dependence, which is required for mTORC1 activation and in consequence Sertoli cell proliferation.

Abstract

The spermatogenic capacity of adult individuals depends on, among other factors, the number of Sertoli cells (SCs) that result from the proliferative waves during development. FSH upregulates SC proliferation at least partly, through the activation of the PI3K/Akt/mTORC1 pathway, among other mechanisms. It is widely known that mTORC1 is a sensor of amino acids. Among amino acids, glutamine acquires relevance since it might contribute to cell cycle progression through the modulation of mTORC1 activity. It has not been studied yet whether glutamine intervenes in FSH-mediated regulation of SC proliferation and cell cycle progression, or if FSH has any effect on glutamine metabolism. Eight-day-old rat SCs were incubated in culture media without glutamine or with glutamine in the absence or presence of a glutamine transporter inhibitor or a glutaminase activity inhibitor under basal conditions or stimulated with FSH. The results obtained show that FSH does not promote SC proliferation and mTORC1 activation in the absence of glutamine. Also, FSH modulates glutamine metabolism increasing glutaminase isoform 2 and reducing glutamine synthetaseexpression. FSH did not promote SC proliferation and mTORC1 activation when glutaminase activity was inhibited. The results suggest that glutamine or its metabolites might cooperate with FSH in the upregulation of SC proliferation through mTORC1. In addition, as FSH modulates glutamine metabolism through the induction of glutaminase isoform 2, the hormonal control of glutamine metabolism might be part of the intricate signaling network triggered by FSH, which is crucial to establish the population of mature SCs that supports the reproductive function.

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Print ISSN:
1470-1626
Online ISSN:
1741-7899

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