EFFECT OF PERIPHERAL NEURAL STIMULATION WITH ALLOPREGNANOLONE ON OVARIAN PHYSIOLOGY

ANTONELLA ROSARIO RAMONA CÁCERES GIMENEZ; CAMPO VERDE ARBOCCÓ, FIORELLA; SANHUEZA, MARÍA DE LOS ÁNGELES; CARDONE, DANIELA ALEJANDRA; GRACIELA BEATRIZ RODRIGUEZ; CASAIS, MARILINA; VEGA OROZCO, ADRIANA SOLEDAD; LACONI, MYRIAM RAQUEL

Torino

Congreso; 12th STEROIDS and NERVOUS SYSTEM MEETING; 2024

Neuroactive steroids can rapidly regulate multiple physiological functions in the central andperipheral nervous systems. The aims of the present study were to determine whetherallopregnanolone (ALLO), administered in low nanomolar and high micromolarconcentrations, can: (i) induce changes in the ovarian progesterone (P4) and estradiol (E2)release; (ii) modify the ovarian mRNA expression of Hsd3b1 (3β-hydroxysteroiddehydrogenase, 3β-HSD)3β-, Akr1c3 (20α-hydroxysteroid dehydrogenase, 20α-HSD), andAkr1c14 (3α-hydroxy steroid oxidoreductase, 3α-HSOR); and (iii) modulate the ovarianexpression of progesterone receptors A and B, α and β estrogenic receptors, luteinizinghormone receptor (LHR) and follicle-stimulating hormone receptor (FSHR). To furthercharacterize ALLO peripheral actions, the effects were evaluated using a superiormesenteric ganglion–ovarian nervous plexus–ovary (SMG–ONP–O) and a denervated ovary(DO) systems. ALLO SMG administration increased P4 concentration in the incubationliquid by decreasing ovarian 20α-HSD mRNA, and it also increased ovarian 3α-HSORmRNA expression. In addition, ALLO neural peripheral modulation induced an increase inthe expression of ovarian LHR, PRA, PRB, and ERα. Direct ALLO administration to theDO decreased E2 and increased P4 concentration in the incubation liquid. The mRNAexpression of 3β-HSD decreased, and 20α-HSD increased. Further, ALLO in the ODsignificantly changed ovarian FSHR and PRA expression. This is the first evidence ofALLO’s direct effect on ovarian steroidogenesis. Our results provide important insightsabout how this neuroactive steroid interacts both with the PNS and the ovary, and thesefindings might help devise some of the pleiotropic effects of neuroactive steroids on femalereproduction. Moreover, ALLO modulation of ovarian physiology might help uncover noveltreatment approaches for reproductive diseases.