Cardinali D P, Vacas M I, Ritta M N, Gejman P V
Centro de Estudios Farmacológicos y de Principios Naturales, (CEFAPRIN), Serrano 665, 1414 Buenos Aires, Argentina.
Neurochem Int. 1983;5(2):185-92. doi: 10.1016/0197-0186(83)90113-4.
Results are discussed indicating that neurotransmitters affect steroid hormone activity not only by controlling via neuroendocrine events the hypophysial-gonadal and hypophysial-adrenal axes, but also by modulating cell responsiveness to steroids in target cells. Hyper- or hypoactivity of pineal nerves result in enhancement or impairment of estradiol and testosterone effects on pineal metabolism in vivo and in vitro. Pineal cytoplasmic and nuclear estrogen and androgen receptors are modulated by norepinephrine released from nerve endings at the pinealocyte level. Neural activity affects the cycle of depletion-replenishment of pineal estrogen receptors following estradiol administration. Another site of modulation of steroid effects on the pinealocytes is the intracellular metabolism of testosterone and progesterone; nerve activity has a positive effect on testosterone aromatization and a negative effect on testosterone and progesterone 5?-reduction. NE activity on the pineal cells is mediated via ?-adrenoceptors and cAMP. In the central nervous system information on the neurotransmitter modulation of steroid hormone action includes the following observations: (a) hypothalamic deafferentation depresses estrogen receptor levels in rat medial basal hypothalamus; (b) changes in noradrenergic transmission affect, via ?-adrenoceptors, the estradiol-induced increase of cytosol progestin receptor concentration in guinea pig hypothalamus; (c) cAMP increases testosterone aromatization in cultured neurons from turtle brain; (d) electrical stimulation of dorsal hippocampus augments, and reserpine or 6-hydroxydopamine treatment decrease, corticoid binding in cat hypothalamus. In the adenohypophysis changes in dopaminergic input after median eminence lesions or bromocriptine treatment of rats result in opposite modifications of pituitary estrogen receptor levels. Therefore all these observations support the view that neurotransmitters can modulate the attachment of steroid hormones to their receptors in target cells.
讨论结果表明，神经递质不仅通过神经内分泌事件控制垂体-性腺轴和垂体-肾上腺轴来影响甾体激素活性，还通过调节靶细胞对甾体激素的反应性来发挥作用。松果体神经的功能亢进或减退会导致雌二醇和睾酮在体内和体外对松果体代谢的作用增强或受损。松果体细胞浆和细胞核中的雌激素和雄激素受体在松果体细胞水平受到神经末梢释放的去甲肾上腺素的调节。神经活动会影响雌二醇给药后松果体雌激素受体的消耗-补充循环。甾体激素对松果体细胞作用的另一个调节位点是睾酮和孕酮的细胞内代谢；神经活动对睾酮的芳香化有正向作用，而对睾酮和孕酮的5α-还原有负向作用。松果体细胞上的去甲肾上腺素活性通过β-肾上腺素能受体和环磷酸腺苷（cAMP）介导。在中枢神经系统中，关于神经递质对甾体激素作用调节的信息包括以下观察结果：（a）下丘脑去传入会降低大鼠内侧基底下丘脑的雌激素受体水平；（b）去甲肾上腺素能传递的变化通过β-肾上腺素能受体影响豚鼠下丘脑雌二醇诱导的胞浆孕激素受体浓度增加；（c）cAMP增加龟脑培养神经元中睾酮的芳香化；（d）海马背侧的电刺激会增强猫下丘脑的皮质激素结合，而利血平或6-羟基多巴胺处理则会降低这种结合。在腺垂体中，大鼠正中隆起损伤或用溴隐亭处理后多巴胺能输入的变化会导致垂体雌激素受体水平的相反改变。因此，所有这些观察结果都支持神经递质可以调节甾体激素与靶细胞中其受体结合的观点。
