Johnston C A, Negro-Vilar A
Reproductive Neuroendocrinology Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Endocrinology. 1988 Jan;122(1):341-50. doi: 10.1210/endo-122-1-341.
The present study was designed to evaluate the possible physiological role of oxytocin (OXY) on PRL release by examining the effect of administration of potent pharmacological antagonists of OXY on the stimulation of PRL secretion observed in vitro from anterior pituitary (AP) cells in response to OXY administration or in a number of in vivo paradigms. OXY caused a dose-related increase in PRL release from dispersed AP cells and short term AP cell cultures which was blocked by administration of the OXY antagonists [1-deaminopenicillamine, 2-O-methyltyrosine, 8-ornithine]vasotocin (dPOMeOVT) or [1-(beta-mercapto-beta,beta-cyclopentamethylene propanoic acid)2-O-methyltyrosine, 8-ornithine]vasotocin (MPOMeOVT), respectively. The antagonists were given in vivo in a dose that completely blocked suckling-induced milk let-down for up to 90 min. Injection of the antagonists did not alter the 5-hydroxytryptophan-induced increase in plasma PRL or the increase associated with acute ether stress or acute suckling stimuli, suggesting that OXY is not a major component involved in the neuroendocrine mechanisms responsible for those particular increases. On the other hand, iv administration of dPOMeOVT or MPOMeOVT prevented the increase in plasma PRL normally observed on the afternoon of proestrus in the cycling female rat. The characteristic surge of LH was also blocked by high doses of these antagonists. These data demonstrate that PRL secretion undergoes a differential regulation, in that OXY appears to play a major role in regulating the increase in plasma PRL observed on the afternoon of proestrus, but apparently provides little, if any, contribution toward the neuroendocrine regulation of the increases in PRL associated with 5-hydroxytryptophan administration, acute ether stress stimulus, or acute suckling stimulus. The data also suggest that OXY receptors located in the AP that are involved in the OXY-induced increase in PRL release may be similar to those OXY receptors located in mammary and uterine tissue, since specific biological effects of OXY in those tissues are effectively blocked by the OXY antagonists dPOMeOVT and MPOMeOVT. A possible role of OXY neurons in the neural mechanisms triggering the LH surge during proestrus is also suggested.
本研究旨在通过检测给予强效催产素（OXY）药理学拮抗剂对体外培养的垂体前叶（AP）细胞在给予OXY后或在多种体内实验范式中观察到的PRL分泌刺激的影响，来评估OXY对PRL释放可能的生理作用。OXY导致分散的AP细胞和短期AP细胞培养物中PRL释放呈剂量依赖性增加，而给予OXY拮抗剂[1-脱氨青霉胺，2-O-甲基酪氨酸，8-鸟氨酸]加压素（dPOMeOVT）或[1-（β-巯基-β，β-环戊亚甲基丙酸）2-O-甲基酪氨酸，8-鸟氨酸]加压素（MPOMeOVT）可分别阻断这种增加。拮抗剂以能完全阻断哺乳诱导的排乳长达90分钟的剂量进行体内给药。注射拮抗剂并未改变5-羟色氨酸诱导的血浆PRL升高或与急性乙醚应激或急性哺乳刺激相关的升高，这表明OXY不是负责这些特定升高的神经内分泌机制的主要组成部分。另一方面，静脉注射dPOMeOVT或MPOMeOVT可阻止正常发情前期下午循环雌性大鼠血浆PRL的升高。高剂量的这些拮抗剂也阻断了LH的特征性激增。这些数据表明PRL分泌受到差异调节，即OXY似乎在调节发情前期下午观察到的血浆PRL升高方面起主要作用，但显然对与5-羟色氨酸给药、急性乙醚应激刺激或急性哺乳刺激相关的PRL升高的神经内分泌调节贡献很小（如果有的话）。数据还表明，参与OXY诱导的PRL释放增加的位于AP的OXY受体可能与位于乳腺和子宫组织中的那些OXY受体相似，因为OXY在这些组织中的特定生物学效应被OXY拮抗剂dPOMeOVT和MPOMeOVT有效阻断。还提示了OXY神经元在发情前期触发LH激增的神经机制中的可能作用。
