Yin Ping, Kawashima Kengo, Arita Jun
Department of Physiology, Yamanashi Medical University, Yamanashi, Japan.
Neuroendocrinology. 2002 Jun;75(6):392-401. doi: 10.1159/000059436.
Estradiol induces surges of prolactin (PRL) and luteinizing hormone (LH) secretion as well as lactotrope proliferation in female rats. We examined whether these hypothalamus-dependent events require the direct action of estradiol on the anterior pituitary gland by selective blockade of its peripheral actions, using ICI182,780 (ICI), an antiestrogen that cannot cross the blood-brain barrier. Injection of ICI into ovariectomized rats, at a dose of 250 microg/day for 4 days, almost completely inhibited estradiol-induced growth of the uterus, proliferation of lactotropes as determined by bromodeoxyuridine incorporation, and afternoon surges of LH secretion. However, ICI only partially inhibited estradiol-induced surges of PRL secretion and had no effect on estradiol-induced tonic inhibition of LH secretion even at the highest dose of 1,000 microg/day. The inhibitory effects of ICI found at 250 microg/day were attributable to its selective peripheral, but not central actions since ICI did not alter hypothalamic expression of progesterone receptors, an estradiol-dependent brain process. Estradiol-induced increases in the number of progesterone receptor-immunoreactive cells in the hypothalamic ventromedial nucleus and the medial preoptic area were not inhibited by this dose of ICI but were inhibited by 500 microg/day tamoxifen, an antiestrogen that can cross the blood-brain barrier. Treatment of cycling female rats with 250 microg/day ICI beginning from diestrus day 2 was also effective in blocking estrous lactotrope proliferation and preovulatory surges of LH secretion but not PRL secretion. Finally, in ovariectomized estradiol-treated pup-deprived lactating rats, ICI did not affect suckling-induced PRL secretion but completely blocked lactotrope proliferation. These results suggest that a direct estradiol action on the anterior pituitary gland is required for lactotrope proliferation and the positive feedback action on LH secretion but not for the secretory surges of PRL or for negative feedback.
雌二醇可诱导雌性大鼠催乳素（PRL）和促黄体生成素（LH）分泌激增以及催乳细胞增殖。我们使用不能穿过血脑屏障的抗雌激素药物ICI182,780（ICI）选择性阻断雌二醇的外周作用，研究了这些依赖下丘脑的事件是否需要雌二醇对垂体前叶的直接作用。以250微克/天的剂量给去卵巢大鼠注射ICI，持续4天，几乎完全抑制了雌二醇诱导的子宫生长、通过溴脱氧尿苷掺入法测定的催乳细胞增殖以及下午LH分泌激增。然而，ICI仅部分抑制了雌二醇诱导的PRL分泌激增，即使在最高剂量1000微克/天时，对雌二醇诱导的LH分泌的紧张性抑制也没有影响。在250微克/天时发现的ICI抑制作用归因于其选择性外周作用而非中枢作用，因为ICI没有改变孕激素受体的下丘脑表达，而孕激素受体表达是一个依赖雌二醇的脑内过程。雌二醇诱导的下丘脑腹内侧核和内侧视前区孕激素受体免疫反应性细胞数量增加不受该剂量ICI的抑制，但受到500微克/天他莫昔芬（一种可穿过血脑屏障的抗雌激素药物）的抑制。从动情后期第2天开始，以250微克/天的剂量用ICI处理处于发情周期的雌性大鼠，也能有效阻断动情期催乳细胞增殖和排卵前LH分泌激增，但对PRL分泌无效。最后，在去卵巢并用雌二醇处理的剥夺幼崽的泌乳大鼠中，ICI不影响哺乳诱导的PRL分泌，但完全阻断了催乳细胞增殖。这些结果表明，雌二醇对垂体前叶的直接作用是催乳细胞增殖和对LH分泌的正反馈作用所必需的，但对PRL分泌激增或负反馈作用则不是必需的。
