Evans J J, Catt K J
Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, Bethesda, Maryland 20892.
J Endocrinol. 1989 Jul;122(1):107-16. doi: 10.1677/joe.0.1220107.
Neurohypophysial hormones stimulate gonadotrophin release from dispersed rat anterior pituitary cells in vitro, acting through receptors distinct from those which mediate the secretory response to gonadotrophin-releasing hormone (GnRH). The LH response to oxytocin was not affected by the presence of the phosphodiesterase inhibitor, methyl isobutylxanthine, but was diminished in the absence of extracellular calcium and was progressively increased as the calcium concentration in the medium was raised to normal. In addition, the calcium channel antagonist, nifedipine, suppressed oxytocin-stimulated secretion of LH. It is likely that the mechanisms of LH release induced by GnRH and neurohypophysial hormones are similar, although stimulation of gonadotrophin secretion is mediated by separate receptor systems. Oxytocin was more active than vasopressin in releasing LH, but less active in releasing ACTH. The highly selective oxytocin agonist, [Thr4,Gly7]oxytocin, elicited concentration-dependent secretion of LH but had little effect on corticotrophin secretion. The neurohypophysial hormone antagonist analogues, [d(CH2)5Tyr(Me)2]vasopressin, [d(CH2)5Tyr(Me)2,Orn8]vasotocin and [d(CH2)5D-Tyr(Et)2Val4,Cit8]vasopressin, inhibited the LH response to both oxytocin and vasopressin. However, [d(CH2)5Tyr(Me)2]vasopressin was much less effective in inhibiting the ACTH response to the neurohypophysial hormones, and [d(CH2)5Tyr-(Me)2,Orn8]vasotocin and [d(CH2)5D-Tyr(Et)2,Val4,Cit8]vasopressin exhibited no inhibitory activity against ACTH release. Thus, agonist and antagonist analogues of neurohypophysial hormones display divergent activities with regard to LH and ACTH responses, and the neuropeptide receptor mediating gonadotroph activation is clearly different from that on the corticotroph. Whereas the corticotroph receptor is a vasopressin-type receptor an oxytocin-type receptor is responsible for gonadotrophin release by neurohypophysial hormones.
神经垂体激素可刺激体外培养的大鼠分散垂体前叶细胞释放促性腺激素，其作用是通过与介导对促性腺激素释放激素（GnRH）分泌反应的受体不同的受体来实现的。促黄体生成素（LH）对催产素的反应不受磷酸二酯酶抑制剂甲基异丁基黄嘌呤的影响，但在细胞外钙缺失时减弱，并且随着培养基中钙浓度升高至正常水平而逐渐增强。此外，钙通道拮抗剂硝苯地平可抑制催产素刺激的LH分泌。GnRH和神经垂体激素诱导LH释放的机制可能相似，尽管促性腺激素分泌的刺激是由不同的受体系统介导的。催产素在释放LH方面比加压素更具活性，但在释放促肾上腺皮质激素（ACTH）方面活性较低。高度选择性的催产素激动剂[Thr4,Gly7]催产素可引起LH的浓度依赖性分泌，但对促肾上腺皮质激素分泌几乎没有影响。神经垂体激素拮抗剂类似物[d(CH2)5Tyr(Me)2]加压素、[d(CH2)5Tyr(Me)2,Orn8]血管紧张素和[d(CH2)5D-Tyr(Et)2Val4,Cit8]加压素可抑制LH对催产素和加压素的反应。然而，[d(CH2)5Tyr(Me)2]加压素在抑制ACTH对神经垂体激素的反应方面效果要差得多，并且[d(CH2)5Tyr-(Me)2,Orn8]血管紧张素和[d(CH2)5D-Tyr(Et)2,Val4,Cit8]加压素对ACTH释放没有抑制活性。因此，神经垂体激素的激动剂和拮抗剂类似物在LH和ACTH反应方面表现出不同的活性，并且介导促性腺激素细胞激活的神经肽受体明显不同于促肾上腺皮质激素细胞上的受体。促肾上腺皮质激素细胞受体是一种加压素型受体，而神经垂体激素释放促性腺激素是由一种催产素型受体负责的。
