Bethea C L, Fahrenbach W H, Sprangers S A, Freesh F
Division of Reproductive Biology, Oregon Regional Primate Research Center, Beaverton 97006.
Endocrinology. 1992 Feb;130(2):895-905. doi: 10.1210/endo.130.2.1733733.
The increase in PRL secretion which follows progesterone (P) administration to estradiol (E)-primed women and monkeys cannot be due to an action of P at the pituitary level because lactotropes do not contain progestin receptors (PR). To further the hypothesis that P increases PRL secretion by an action in the hypothalamus, PR-expressing neurons were studied in free-ranging and steroid-manipulated monkeys using immunocytochemistry with a monoclonal antibody to human PR. Specific PR immunoreactivity is localized in the nucleus of individual hypothalamic neurons. Male and female adult and juvenile macaque hypothalami contain significant populations of PR-positive neurons throughout the anterior and medial basal hypothalamus. Ovariectomy decreases, but does not abolish, the number of neurons expressing PR. PR expression was not altered in the supraoptic nucleus (SON) by ovariectomy. Estrogen treatment for 28 days caused a significant increase in the number of PR-positive neurons in the medial preoptic area, the ventro-medial nucleus, the arcuate nucleus, and the median eminence, but not in the SON. P treatment added to the E treatment from day 14 to day 28 did not alter the number of PR-positive neurons in any area. These data suggest that PR may be constitutively expressed in the magnocellular neurons of the SON and in certain other cells throughout the hypothalamus. E induces PR in a large proportion of neurons in the medial basal hypothalamus and this action is not blocked by subsequent P treatment. The inability of P to down-regulate PR in the hypothalamus differs from the reproductive tract and pituitary. Indeed, this observation is consistent with the fact that PRL secretion remains elevated during chronic P administration.
对用雌二醇（E）预处理过的女性和猴子给予孕酮（P）后，催乳素（PRL）分泌增加，这并非是由于P作用于垂体水平，因为催乳细胞不含有孕激素受体（PR）。为进一步验证P通过作用于下丘脑来增加PRL分泌这一假说，使用抗人PR单克隆抗体通过免疫细胞化学方法，对自由放养和经类固醇处理的猴子中表达PR的神经元进行了研究。特异性PR免疫反应定位于单个下丘脑神经元的细胞核中。成年和幼年雄性及雌性猕猴的下丘脑，在前部和内侧基底下丘脑各处都含有大量PR阳性神经元。卵巢切除会减少但不会消除表达PR的神经元数量。卵巢切除对视上核（SON）中的PR表达没有影响。雌激素治疗28天会导致内侧视前区、腹内侧核、弓状核和正中隆起中PR阳性神经元数量显著增加，但对视上核无影响。从第14天到第28天，在雌激素治疗基础上加用P治疗，并未改变任何区域PR阳性神经元的数量。这些数据表明，PR可能在下丘脑视上核的大细胞神经元以及下丘脑其他某些细胞中组成性表达。雌激素在内侧基底下丘脑的大部分神经元中诱导PR表达，且这一作用不会被随后的P治疗所阻断。P无法下调下丘脑PR的情况与生殖道和垂体不同。实际上，这一观察结果与长期给予P期间PRL分泌持续升高的事实是一致的。
