Direct Actions of Kisspeptins on GnRH Neurons Permit Attainment of Fertility but Are Insufficient to Fully Preserve Gonadotropic Axis Activity

Overview

Journal Sci Rep

Specialty Science

Date 2016 Jan 13

PMID 26755241

Citations 31

Authors

Silvia Leon

Alexia Barroso

Maria J Vazquez

David Garcia-Galiano

Maria Manfredi-Lozano

Francisco Ruiz-Pino

Violeta Heras

Antonio Romero-Ruiz

Juan Roa

Gunther Schutz

Milen Kirilov

Francisco Gaytan

Leonor Pinilla

Manuel Tena-Sempere

Affiliations

Soon will be listed here.

Abstract

Kisspeptins, ligands of the receptor, Gpr54, are potent stimulators of puberty and fertility. Yet, whether direct kisspeptin actions on GnRH neurons are sufficient for the whole repertoire of their reproductive effects remains debatable. To dissect out direct vs. indirect effects of kisspeptins on GnRH neurons in vivo, we report herein the detailed reproductive/gonadotropic characterization of a Gpr54 null mouse line with selective re-introduction of Gpr54 expression only in GnRH cells (Gpr54(-/-)Tg; rescued). Despite preserved fertility, adult rescued mice displayed abnormalities in gonadal microstructure, with signs of precocious ageing in females and elevated LH levels with normal-to-low testosterone secretion in males. Gpr54(-/-)Tg rescued mice showed also altered gonadotropin responses to negative feedback withdrawal, while luteinizing hormone responses to various gonadotropic regulators were variably affected, with partially blunted relative (but not absolute) responses to kisspeptin-10, NMDA and the agonist of tachykinin receptors, NK2R. Our data confirm that direct effects of kisspeptins on GnRH cells are sufficient to attain fertility. Yet, such direct actions appear to be insufficient to completely preserve proper functionality of gonadotropic axis, suggesting a role of kisspeptin signaling outside GnRH cells.

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