Lima Fernanda Barbosa, Szawka Raphael Escorsim, Anselmo-Franci Janete Aparecida, Franci Celso Rodrigues
Departamento de Fisiologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão, Preto, SP, Brazil.
Brain Res. 2007 Apr 20;1142:37-45. doi: 10.1016/j.brainres.2007.01.045. Epub 2007 Jan 20.
The neurons that produce gonadotrophin-releasing hormone (GnRH) are mainly found in the medial preoptic area (MPOA) and constitute a common final pathway to the control of luteinizing hormone (LH) surge on proestrus. The control of GnRH secretion depends on several neurotransmitters, such as serotonin (5-HT), noradrenaline (NA), dopamine (DA) and nitric oxide (NO). The aim of this work was to study the profile of 5-HT, catecholamines and their main metabolites in the MPOA throughout the estrous cycle and their interactions with NO system in this area to control LH surge. For this purpose, the following were evaluated: (I) the effect of pargyline (a monoamine oxidase inhibitor) acute treatment on plasma LH secretion throughout the estrous cycle, correlated with changes of 5-HT, DA and NA content as well as activity and expression of neuronal NO synthase (nNOS) within MPOA; (II) the effect of 5,7-dihydroxitriptamine (a drug that depletes 5-HT) microinjection into MPOA on plasma LH in ovariectomized rats treated with oil, estradiol (E(2)) or E(2) plus progesterone (P(4)). Pargyline prevented LH surge on proestrus without altering its basal secretion. Throughout the estrous cycle, pargyline augmented both 5-HT and DA contents in approximately 300% and NA content in 50% in the MPOA. During proestrus, pargyline stimulated nNOS activity at 9 h and inhibited it at 11 h. nNOS expression was inhibited by pargyline at 15 h. Depletion of 5-HT content in the MPOA increased LH secretion in ovariectomized rats treated with E(2) plus P(4), but it did not modify in rats treated with either oil or E(2). Therefore, the present data show that pargyline treatment can inhibit proestrus LH surge through a mechanism that may involve 5-HT and NO systems in the MPOA. Moreover, the effect of 5-HT in the MPOA for limiting LH surge seems to depend on plasma levels of E(2) and P(4).
产生促性腺激素释放激素(GnRH)的神经元主要位于内侧视前区(MPOA),是控制发情前期促黄体生成素(LH)激增的共同最终途径。GnRH分泌的控制取决于多种神经递质,如血清素(5-HT)、去甲肾上腺素(NA)、多巴胺(DA)和一氧化氮(NO)。这项工作的目的是研究发情周期中MPOA内5-HT、儿茶酚胺及其主要代谢产物的概况,以及它们在该区域与NO系统的相互作用对LH激增的控制。为此,进行了以下评估:(I)优降宁(一种单胺氧化酶抑制剂)急性处理对整个发情周期血浆LH分泌的影响,与MPOA内5-HT、DA和NA含量的变化以及神经元型一氧化氮合酶(nNOS)的活性和表达相关;(II)向经油、雌二醇(E₂)或E₂加孕酮(P₄)处理的去卵巢大鼠的MPOA内微量注射5,7-二羟基色胺(一种耗尽5-HT的药物)对血浆LH的影响。优降宁可防止发情前期的LH激增,而不改变其基础分泌。在整个发情周期中,优降宁使MPOA内的5-HT和DA含量增加约300%,NA含量增加50%。在发情前期,优降宁在9小时刺激nNOS活性,在11小时抑制其活性。在15小时,优降宁可抑制nNOS表达。MPOA内5-HT含量的耗尽增加了经E₂加P₄处理的去卵巢大鼠的LH分泌,但对经油或E₂处理的大鼠没有影响。因此,目前的数据表明,优降宁处理可通过一种可能涉及MPOA内5-HT和NO系统的机制抑制发情前期LH激增。此外,MPOA内5-HT对限制LH激增的作用似乎取决于血浆E₂和P₄水平。