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

•Pharmacological doses of progesterone (P4) and estradiol (E2) inhibited hypothalamic GnRH expression.•Physiological doses of P4 and E2 differentially altered GnRH pulsatile release frequency or genomic expression.•The modulation of GnRH synthesis and release is subjected to different levels of acti...

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Published in:The Journal of steroid biochemistry and molecular biology 2020-06, Vol.200, p.105627-105627, Article 105627
Main Authors: Inserra, Pablo I.F., Charif, Santiago E., Fidel, Victoria, Giacchino, Mariela, Schmidt, Alejandro R., Villarreal, Federico M., Proietto, Sofía, Cortasa, Santiago A., Corso, María C., Gariboldi, María C., Leopardo, Noelia P., Fraunhoffer, Nicolás A., Di Giorgio, Noelia P., Lux-Lantos, Victoria A., Halperin, Julia, Vitullo, Alfredo D., Dorfman, Verónica B.
Format: Article
Language:English
Subjects:
17β-Estradiol
Estradiol
Estrogen receptors
Gene expression
Gestation
GnRH
Gonadotropin-releasing hormone
Gonadotropins
Hormones
Hypothalamus
Lagostomus maximus
Ovariectomy
Pituitary
Pituitary (anterior)
Pregnancy
Progesterone
Progesterone receptors
RNA modification
Steroid hormones
Vizcacha
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Summary:•Pharmacological doses of progesterone (P4) and estradiol (E2) inhibited hypothalamic GnRH expression.•Physiological doses of P4 and E2 differentially altered GnRH pulsatile release frequency or genomic expression.•The modulation of GnRH synthesis and release is subjected to different levels of action of steroid hormones.•E2 displayed a rapid effect on GnRH release frequency and a long-term effect on its mRNA expression.•The fine action of E2 and P4 enables the hypothalamic activity during the pregnancy of this mammal. The South American plains vizcacha, Lagostomus maximus, is the only mammal described so far that shows expression 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 steroid hormones on the modulation of the hypothalamic-pituitary-ovarian (HPO) axis. By using both in vivo and ex vivo approaches, we have found that pharmacological doses of progesterone (P4) and estradiol (E2) produced an inhibition in the expression of hypothalamic GnRH, while physiological doses produced a differential effect on the pulsatile release frequency or genomic expression of GnRH. Our ex vivo experiment indicates that a short-term effect 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 classical nuclear ERs-PRs pathway, would produce the modification of GnRH mRNA expression during the GnRH pre-ovulatory surge. Particularly, P4 induced a rise in GnRH mRNA expression and protein release with a decrease in its 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 activity during the pregnancy of this mammal.
ISSN:0960-0760
1879-1220
DOI:10.1016/j.jsbmb.2020.105627