Frungieri Mónica B, Mayerhofer Artur, Zitta Karina, Pignataro Omar P, Calandra Ricardo S, Gonzalez-Calvar Silvia I
Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Vuelta de Obligado 2490, (1428) Buenos Aires, Argentina.
Endocrinology. 2005 Mar;146(3):1541-52. doi: 10.1210/en.2004-0990. Epub 2004 Nov 18.
Besides the hypothalamus and pituitary, melatonin action at the testicular level has been recently suggested. Therefore, we investigated in the Syrian hamster, a well-characterized seasonal breeder, melatonin action on Leydig cells, testicular expression of melatonergic receptors, and possible interactions between melatonin receptors and the previously identified testicular serotoninergic and CRH systems. In isolated Leydig cells from active testes of adult hamsters kept in a long-day (14 h light, 10 h dark) photoperiod and from regressed testes of adult animals exposed to a short-day photoperiod during 16 wk (6 h light, 18 h dark), melatonin significantly reduced human chorionic gonadotropin-stimulated production of cAMP and the main androgens: testosterone and androstane-3alpha,17beta-diol, respectively, and decreased the expression of steroidogenic acute regulatory protein, P450 side chain cleavage, 3beta-hydroxysteroid dehydrogenase and 17beta-hydroxysteroid dehydrogenase. In Leydig cells exposed to a short-day photoperiod during 16 wk, melatonin stimulated the conversion of testosterone into 5alpha-reduced androgens by inducing 5alpha-reductase isoform 1, and controlled androstane-3alpha,17beta-diol production by inhibiting 3alpha-hydroxysteroid dehydrogenase expression. Melatonin subtype (mel1a) receptors were detected in Leydig cells. Although the local serotonin system did not mediate melatonin action on androgen production, melatonergic effect on steroidogenesis involved the interaction between mel1a receptors and the inhibitory CRH system. Moreover, melatonin significantly increased CRH mRNA levels and production in hamster Leydig cells expressing CRH subtype 1 receptors. Our studies indicate that melatonin may act as a local inhibitor of human chorionic gonadotropin-stimulated cAMP and androgen production through mel1a receptors, down-regulation of steroidogenic acute regulatory protein, and key steroidogenic enzymes expression and its interaction with the local CRH system.
除下丘脑和垂体外，最近有研究表明褪黑素在睾丸水平也有作用。因此，我们以叙利亚仓鼠为研究对象，这是一种具有明确季节性繁殖特征的动物，研究了褪黑素对睾丸间质细胞的作用、睾丸中褪黑素能受体的表达，以及褪黑素受体与先前鉴定的睾丸5-羟色胺能和促肾上腺皮质激素释放激素（CRH）系统之间可能的相互作用。在处于长日照（14小时光照，10小时黑暗）光周期的成年仓鼠活跃睾丸以及在16周内暴露于短日照光周期（6小时光照，18小时黑暗）的成年动物退化睾丸中分离出的间质细胞中，褪黑素显著降低了人绒毛膜促性腺激素刺激的环磷酸腺苷（cAMP）生成以及主要雄激素（分别为睾酮和雄烷-3α,17β-二醇）的生成，并降低了类固醇生成急性调节蛋白、细胞色素P450侧链裂解酶、3β-羟基类固醇脱氢酶和17β-羟基类固醇脱氢酶的表达。在16周内暴露于短日照光周期的间质细胞中，褪黑素通过诱导5α-还原酶同工型1刺激睾酮向5α-还原雄激素的转化，并通过抑制3α-羟基类固醇脱氢酶的表达来控制雄烷-3α,17β-二醇的生成。在间质细胞中检测到了褪黑素亚型（mel1a）受体。虽然局部5-羟色胺系统并未介导褪黑素对雄激素生成的作用，但褪黑素对类固醇生成的影响涉及mel1a受体与抑制性CRH系统之间的相互作用。此外，褪黑素显著增加了表达CRH亚型1受体的仓鼠间质细胞中CRH信使核糖核酸（mRNA）水平和生成量。我们的研究表明，褪黑素可能通过mel1a受体、下调类固醇生成急性调节蛋白和关键类固醇生成酶的表达及其与局部CRH系统的相互作用，作为人绒毛膜促性腺激素刺激的cAMP和雄激素生成的局部抑制剂。
