Seal L J, Small C J, Kim M S, Stanley S A, Taheri S, Ghatei M A, Bloom S R
Endocrine Unit, Imperial College School of Medicine, Hammersmith Hospital, London, UK.
Endocrinology. 2000 May;141(5):1909-12. doi: 10.1210/endo.141.5.7528.
Prolactin releasing peptide (PrRP) was originally isolated as an endogenous hypothalamic ligand for the hGR3 orphan receptor. It has been shown to release prolactin from dispersed pituitaries harvested from lactating female rats and only at very high doses in cycling females. PrRP is reported to have no effect on prolactin production from dispersed pituitary cells harvested from males. The CNS distribution of this peptide suggested a role for PrRP in the control of the hypothalamo-pituitary axis. The aim of this study was to examine the actions of PrRP (1-31) on circulating pituitary hormones following intracerebroventricular (ICV) injection in male rats and to investigate the mechanism of PrRP's effect by measurement of hypothalamic releasing factors in vitro. In our experiments, PrRP (1-31) did not release LH, FSH, TSH, growth hormone or prolactin directly from dispersed male pituitary cells in vitro. We have shown for the first time that following ICV injection of PrRP (1-31) 5 nmol there was a highly significant simulation of plasma LH that began at 10 minutes and was maintained over the course of the experiment (at 60 minutes PrRP 5 nmol 2.2 +/- 0.2 vs. saline 0.5 +/- 0.1 ng/ml, p<0.001). Plasma FSH increased at 20 minutes following ICV injection (PrRP 5nmol 10.8 +/- 2.0 ng/ml vs. saline 5.1 +/- 0.5, p<0.01). Total plasma testosterone increased at 60 minutes post injection (PrRP 5nmol 9.2 +/- 1.6 vs. saline 3.5 +/- 0.6 nmol/l, p<0.01). There was no significant alteration in plasma prolactin levels. PrRP significantly increased the release of LHRH from hypothalamic explants in vitro (PrRP 100nmol/l 180.5 +/- 34.5% of the basal secretion, p<0.05). PrRP (100nmol/l) also increased the following hypothalamic peptides involved in the control of pituitary hormone release, vasoactive intestinal peptide (VIP) 188.1 +/- 24.6% and galanin 153.8 +/- 13.0% (both p<0.001 vs. basal secretion) but had no effect on orexin A secretion. These results suggest a role for PrRP in the control of gonadotrophin secretion acting via a hypothalamic mechanism involving the release of LHRH.
催乳素释放肽（PrRP）最初是作为孤儿受体hGR3的一种内源性下丘脑配体被分离出来的。已证明它能从泌乳雌性大鼠分离出的垂体中释放催乳素，而在处于发情周期的雌性大鼠中，只有在非常高的剂量下才会释放。据报道，PrRP对从雄性大鼠分离出的垂体细胞产生催乳素没有影响。这种肽在中枢神经系统的分布表明其在控制下丘脑 - 垂体轴方面发挥作用。本研究的目的是检查脑室内（ICV）注射PrRP（1 - 31）后对雄性大鼠循环垂体激素的作用，并通过体外测量下丘脑释放因子来研究PrRP作用的机制。在我们的实验中，PrRP（1 - 31）在体外不能直接从分离出的雄性垂体细胞中释放促黄体生成素（LH）、促卵泡生成素（FSH）、促甲状腺激素（TSH）、生长激素或催乳素。我们首次表明，脑室内注射5 nmol PrRP（1 - 31）后，血浆LH在10分钟时开始受到高度显著的刺激，并在实验过程中持续存在（60分钟时，PrRP 5 nmol组为2.2±0.2 ng/ml，生理盐水组为0.5±0.1 ng/ml，p<0.001）。脑室内注射后20分钟血浆FSH增加（PrRP 5 nmol组为10.8±2.0 ng/ml，生理盐水组为5.1±0.5 ng/ml，p<0.01）。注射后60分钟血浆总睾酮增加（PrRP 5 nmol组为9.2±1.6 nmol/l，生理盐水组为$3.5\pm0.6$ nmol/l，p<0.01）。血浆催乳素水平没有显著变化。PrRP在体外显著增加下丘脑外植体中促性腺激素释放激素（LHRH）的释放（PrRP 100 nmol/l组为基础分泌的180.5±34.5%，p<0.05）。PrRP（100 nmol/l）还增加了以下参与控制垂体激素释放的下丘脑肽，血管活性肠肽（VIP）为188.1±24.6%，甘丙肽为153.8±13.0%（与基础分泌相比，两者p<0.001），但对食欲素A的分泌没有影响。这些结果表明PrRP通过涉及LHRH释放的下丘脑机制在控制促性腺激素分泌方面发挥作用。
Zotero 插件