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.
J Endocrinol. 2023 Jun 21;258(1). doi: 10.1530/JOE-23-0026. Print 2023 Jul 1.
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.
神经活性甾体可迅速调节中枢和外周神经系统的多种生理功能。本研究旨在确定低纳摩尔和高微摩尔浓度的别孕烯醇酮（ALLO）是否可以：（i）诱导卵巢孕酮（P4）和雌二醇（E2）释放的变化；（ii）改变卵巢 Hsd3b1（3β-羟甾脱氢酶，3β-HSD）3β-、Akr1c3（20α-羟甾脱氢酶，20α-HSD）和 Akr1c14（3α-羟甾氧化还原酶，3α-HSOR）的 mRNA 表达；和（iii）调节卵巢孕激素受体 A 和 B、α 和 β 雌激素受体、促黄体生成素受体（LHR）和卵泡刺激素受体（FSHR）的表达。为了进一步表征 ALLO 的外周作用，使用肠系膜上神经节-卵巢神经丛-卵巢（SMG-ONP-O）和去神经卵巢（DO）系统评估了这些作用。ALLO SMG 给药通过降低卵巢 20α-HSD mRNA 增加孵育液中的 P4 浓度，同时还增加了卵巢 3α-HSOR mRNA 的表达。此外，ALLO 神经外周调节诱导卵巢 LHR、PRA、PRB 和 ERα 的表达增加。直接向 DO 给予 ALLO 会降低孵育液中的 E2 并增加 P4 浓度。3β-HSD 的 mRNA 表达减少，20α-HSD 增加。此外，OD 中的 ALLO 显着改变了卵巢 FSHR 和 PRA 的表达。这是 ALLO 直接影响卵巢甾体生成的第一个证据。我们的研究结果提供了关于这种神经活性甾体如何与 PNS 和卵巢相互作用的重要见解，这些发现可能有助于设计神经活性甾体对女性生殖的一些多效性影响。此外，ALLO 对卵巢生理学的调节可能有助于揭示治疗生殖疾病的新方法。
