Effect of peripheral neural stimulation with allopregnanolone on ovarian physiology

Abstract

Neuroactive steroids can rapidly regulate multiple physiological functions on the central and peripheral nervous systems. The aims of the present study were to determine whether allopregnanolone (ALLO), administered in a low nanomolar and a high micromolar concentrations, can: a) induce changes in the ovarian progesterone (P4) and estradiol (E2) release, b) modify the ovarian mRNA expression of 3 β-HSD, 20 α-HSD and 3 α-HSD, c) modulate the ovarian expression of progesterone receptors A and B, α and β estrogenic receptors, LH receptor (LHR) and FSH receptor (FSHR). To further characterize ALLO peripheral actions, the effects were evaluated using a superior mesenteric ganglion-ovarian nervous plexus-ovary (SMG-ONP-O) and a denervated ovary (DO) systems. ALLO SMG administration increased P4 concentration in the incubation liquid, by decreasing ovarian 20α-HSD mRNA, it also increased ovarian 3α-HSOR mRNA expression. In addition, ALLO neural peripheral modulation induced an increase in the expression of ovarian LHR, PRA, PRB, and ERα. Direct ALLO administration to the DO decreased E2 and increased P4 concentration in the incubation liquid. The mRNA expression of 3β-HSD decreased, and 20α-HSD increased. Further, ALLO in the OD significantly changed ovarian FSHR, and PRA expression. This is the first evidence of ALLO direct effect on ovarian steroidogenesis. Our results provide important insights about how this neuroactive steroid interacts both with the PNS and the ovary, these findings might help devise some of the pleiotropic effects of neuroactive steroids on female reproduction. Moreover, ALLO modulation of ovarian physiology might help uncover novel treatment approaches for reproductive diseases.

Local effect of allopregnanolone in rat ovarian steroidogenesis, follicular and corpora lutea development

“…The ALLO concentration of 6 µM was chosen for these studies based on a concentration–response curve (data not shown) and previous works. It was the pharmacological concentration with the greatest effects on ovarian physiology 19 , 22 .…”

“…Moreover, it can modulate a variety of behaviors, such as reproductive 10 – 13 , social, exploratory and affective conducts 14 – 16 . Previous work from our laboratory reported ALLO actions over the hypothalamic–pituitary–gonadal axis when administered via ICV 17 – 19 and its effects on the ovarian peripheral innervation using an ex vivo culture of the superior mesenteric ganglion- ovarian nervous plexus—ovarian system 20 – 22 . These findings led us to consider ALLO not only as a modulator of central function but also of ovarian physiology.…”