Effect of peripheral neural stimulation with allopregnanolone on ovarian physiology

in Journal of Endocrinology
Authors:
Antonella Rosario Ramona Cáceres Laboratorio de Fisiopatología Ovárica, Instituto de Medicina y Biología Experimental de Cuyo (IMBECU – CONICET Mendoza), Mendoza, Argentina
Facultad de Ingeniería y Facultad de Ciencias Médicas, Universidad de Mendoza, Mendoza, Argentina

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Fiorella Campo Verde Arboccó Laboratorio de Fisiopatología Ovárica, Instituto de Medicina y Biología Experimental de Cuyo (IMBECU – CONICET Mendoza), Mendoza, Argentina

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María de los Ángeles Sanhueza Laboratorio de Fisiopatología Ovárica, Instituto de Medicina y Biología Experimental de Cuyo (IMBECU – CONICET Mendoza), Mendoza, Argentina

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Daniela Alejandra Cardone Laboratorio de Fisiopatología Ovárica, Instituto de Medicina y Biología Experimental de Cuyo (IMBECU – CONICET Mendoza), Mendoza, Argentina

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Graciela Beatriz Rodriguez Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, San Luis, Argentina

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Marilina Casais Laboratorio de Biología de la Reproducción (LABIR), Universidad Nacional de San Luis, San Luis, Argentina

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Adriana Soledad Vega Orozco Laboratorio de Biología de la Reproducción (LABIR), Universidad Nacional de San Luis, San Luis, Argentina

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Myriam Raquel Laconi Laboratorio de Fisiopatología Ovárica, Instituto de Medicina y Biología Experimental de Cuyo (IMBECU – CONICET Mendoza), Mendoza, Argentina
Facultad de Ingeniería y Facultad de Ciencias Médicas, Universidad de Mendoza, Mendoza, Argentina

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Correspondence should be addressed to M R Laconi: mlaconi@mendoza-conicet.gob.ar or mlaconi@yahoo.com

*(A R R Cáceres, F Campo Verde Arboccó, A S Vega Orozco and M R Laconi contributed equally to this work)

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Neuroactive steroids can rapidly regulate multiple physiological functions in the central and peripheral nervous systems. The aims of the present study were to determine whether allopregnanolone (ALLO), administered in low nanomolar and high micromolar concentrations, can: (i) induce changes in the ovarian progesterone (P4) and estradiol (E2) release; (ii) modify the ovarian mRNA expression of Hsd3b1 (3β-hydroxysteroid dehydrogenase, 3β-HSD)3β-, Akr1c3 (20α-hydroxysteroid dehydrogenase, 20α-HSD), and Akr1c14 (3α-hydroxy steroid oxidoreductase, 3α-HSOR)); and (iii) modulate the ovarian expression of progesterone receptors A and B, α and β estrogenic receptors, luteinizing hormone receptor (LHR) and follicle-stimulating hormone 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, and 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’s direct effect on ovarian steroidogenesis. Our results provide important insights about how this neuroactive steroid interacts both with the PNS and the ovary, and 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.

 

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