Rapid actions of the neurosteroid Allopregnanolone in steroidogenesis: central and peripheral modulation

CACERES, A. R.R.; VEGA OROZCO, ADRIANA; CABRERA, RICARDO J; LACONI M.R

JOURNAL OF NEUROENDOCRINOLOGY.

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2020

0953-8194

The aim of this work was to determine if an intracerebroventricular administration of allopregnanolone (ALLO) rapidly modifies the hypothalamic and ovarian 3β-hydroxysteroid dehydrogenase (3β-HSD) enzymatic activity and gene expression on an in vivo and ex vivo systems in proestrus (PE) and dioestrus I (DI) day rats. Experimental groups were injected with allopregnanolone, bicuculline and bicuculline plus allopregnanolone. The animals were sacrificed 5 - 6 minutes after the drug administration. In the in vivo experiment, the hypothalamus, ovaries and serum were extracted. In the ex vivo experiment, the Superior Mesenteric Ganglion - Ovarian Nerve Plexus - ovary system was extracted and incubated for 15, 30, 60 and 120 minutes in a Krebs Ringer buffer at 37 ºC in a metabolic bath. The ovarian compartment fluid was used to determine progesterone by radioimmunoanalysis. Results indicate that allopregnanolone causes a decrease in the hypothalamic and ovarian 3β-HSD enzymatic activity during PE in the in vivo experiments. No changes were observed in the gene expression during this stage. During DI, Allopregnanolone increased the hypothalamic and ovarian 3β-HSD activity and gene expression. The ovarian 3β-HSD activity increased in both stages in the ex vivo SMG-ONP-Ovary system, but gene expression increased only during DI. Progesterone increased in the ovarian incubation liquid in both stages. All findings were reversed by an intracerebroventricular injection of bicuculline before allopregnanolone. Ovarian steroidogenic changes could be attributed to signals coming from ganglionar neurons, which are affected by the acute central neurosteroid stimulation. The intracerebroventricular administration of allopregnanolone through the GABAergic system altered 3β-HSD activity and gene expression modulating the neuroendocrine axis. In the present study, we explored if a central administration of ALLO modifies the neural pathway that regulates ovarian steroidogenesis. We found that ALLO can alter the neural signals from the CNS thus regulating ovarian and hypothalamic progesterone secretion.