O'Conner J L, Wade M F, Brann D W, Mahesh V B
Department of Physiology and Endocrinology, Medical College of Georgia, Augusta 30912-3000, USA.
J Steroid Biochem Mol Biol. 1995 May;52(5):497-504. doi: 10.1016/0960-0760(95)00011-n.
In a previous study we reported that in vivo estrogen-priming alone, without subsequent progesterone-treatment, was sufficient to maximize NPY potentiation of gonadotropin hormone-releasing hormone responsiveness exhibited in vitro by the rat anterior pituitary. This observation suggests that the necessity, as reported by others, for both estrogen-priming and progesterone-treatment to maximize NPY potentiation of GnRH responsiveness in vivo may be due to progesterone acting primarily at the hypothalamus. Consequently, the current study was performed to determine whether progesterone facilitates gonadotropin secretion in vivo by acting to stimulate hypothalamic synthesis of NPY and the subsequent elevation of anterior pituitary tissue levels of NPY. Intact immature female rats were injected with estradiol at 1700 h on days 27 and 28. On day 29 at 0900 h, the animals received an injection of progesterone (2 mg/kg) or vehicle and were subsequently sacrificed at 1200, 1330 and 1500 h. Rats which received only estradiol injections were used as controls. Surge levels of serum LH and FSH were observed at 1330 and 1500 h. Hypothalamic levels of NPY mRNA at 1200 h on day 29 were higher (P < 0.01) in estradiol-primed rats which received progesterone; there was no accompanying statistically significant change in hypothalamic NPY content. NPY content in the anterior pituitary was significantly increased (P < 0.01) at 1200 h on day 29 in estradiol-primed rats which received progesterone; there was no accompanying significant change in anterior pituitary NPY mRNA levels. Hypothalamic GnRH mRNA content was significantly increased (P < 0.01) at 1330 h on day 29 concomitant with the peak of the gonadotropin surge in the estradiol-primed, progesterone-treated rat. The data indicate that progesterone modulates hypothalamic NPY mRNA and anterior pituitary NPY levels as well as GnRH mRNA levels and that modulation of NPY levels in the hypothalamic-pituitary axis occurs prior to modulation of GnRH gene expression. These studies support the hypothesis that in the estrogen-primed rat, progesterone facilitates the induction of the gonadotropin surge by maintaining hypothalamic synthesis of NPY as well as by modulating anterior pituitary NPY tissue levels.
在先前的一项研究中，我们报告称，仅进行体内雌激素预处理，而不进行后续的孕激素处理，就足以使大鼠垂体前叶在体外表现出的促性腺激素释放激素反应性的神经肽Y（NPY）增强作用最大化。这一观察结果表明，其他人所报道的雌激素预处理和孕激素处理两者对于在体内使GnRH反应性的NPY增强作用最大化的必要性，可能是由于孕激素主要作用于下丘脑。因此，进行了当前这项研究，以确定孕激素是否通过刺激下丘脑NPY的合成以及随后提高垂体前叶组织中NPY的水平，来促进体内促性腺激素的分泌。在第27天和第28天的17:00给完整的未成年雌性大鼠注射雌二醇。在第29天的09:00，给动物注射孕激素（2mg/kg）或溶剂，随后在12:00、13:30和15:00处死。仅接受雌二醇注射的大鼠用作对照。在13:30和15:00观察到血清促黄体生成素（LH）和促卵泡生成素（FSH）的峰值水平。在接受孕激素的雌二醇预处理大鼠中，第29天12:00时下丘脑NPY mRNA水平较高（P<0.01）；下丘脑NPY含量没有伴随的统计学显著变化。在接受孕激素的雌二醇预处理大鼠中，第29天12:00时垂体前叶中的NPY含量显著增加（P<0.01）；垂体前叶NPY mRNA水平没有伴随的显著变化。在第29天13:30时，下丘脑GnRH mRNA含量显著增加（P<0.01），此时正值接受雌二醇预处理和孕激素处理大鼠中促性腺激素峰值出现的时候。数据表明，孕激素调节下丘脑NPY mRNA、垂体前叶NPY水平以及GnRH mRNA水平，并且下丘脑 - 垂体轴中NPY水平的调节发生在GnRH基因表达调节之前。这些研究支持这样的假说，即在经雌激素预处理的大鼠中，孕激素通过维持下丘脑NPY的合成以及调节垂体前叶NPY组织水平，促进促性腺激素峰值的诱导。
