The key action of estradiol and progesterone enables GnRH delivery during gestation in the South American plains vizcacha, Lagostomus maximus

INSERRA, PABLO I.F.; GIACCHINO, MARIELA; PROIETTO, SOFÍA; GARIBOLDI, MARÍA C.; DI GIORGIO, NOELIA P.; VITULLO, ALFREDO D.; CHARIF, SANTIAGO E.; SCHMIDT, ALEJANDRO R.; CORTASA, SANTIAGO A.; LEOPARDO, NOELIA P.; LUX-LANTOS, VICTORIA A.; DORFMAN, VERÓNICA B.; FIDEL, VICTORIA; VILLARREAL, FEDERICO M.; CORSO, MARÍA C.; FRAUNHOFFER, NICOLÁS A.; HALPERIN, JULIA

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY

PERGAMON-ELSEVIER SCIENCE LTD

Año: 2020 vol. 200

0960-0760

The South American plains vizcacha, Lagostomus maximus, is the only mammal described so far that showsexpression of estrogen receptors (ERs) and progesterone receptors (PRs) in gonadotropin-releasing hormone(GnRH) neurons. This animal therefore constitutes an exceptional model for the study of the effect of steroidhormones on the modulation of the hypothalamic-pituitary-ovarian (HPO) axis. By using both in vivo and ex vivoapproaches, we have found that pharmacological doses of progesterone (P4) and estradiol (E2) produced aninhibition in the expression of hypothalamic GnRH, while physiological doses produced a differential effect onthe pulsatile release frequency or genomic expression of GnRH. Our ex vivo experiment indicates that a shorttermeffect of E2 modulates the frequency of GnRH release pattern that would be associated with membrane ERs.On the other hand, our in vivo approach suggests that a long-term effect of E2, acting through the classicalnuclear ERs-PRs pathway, would produce the modification of GnRH mRNA expression during the GnRH preovulatorysurge. Particularly, P4 induced a rise in GnRH mRNA expression and protein release with a decrease inits release frequency. These results suggest different levels of action of steroid hormones on GnRH modulation.We conclude that the fine action of E2 and P4 constitute the key factor to enable the hypothalamic activityduring the pregnancy of this mammal.