Kelner K L, Peck E J
J Neurosci Res. 1984;11(1):79-89. doi: 10.1002/jnr.490110109.
In the rat, it is generally accepted that the primary site of estrogen's stimulatory (positive) effects on serum LH is the preoptic area-anterior hypothalamus (POA/AH). In contrast, the primary site of estrogen's inhibitory (negative) effects on serum LH levels has not been conclusively identified. There is evidence to suggest both a medial basal hypothalamic (MBH) and an anterior pituitary site of action. The present studies utilized a unique characteristic of these estrogen effects to investigate their putative loci. Extensive dose-response curves of estrogen's induction of positive and negative feedback indicated that the negative feedback response was activated at a lower concentration of serum estradiol than the positive feedback response. The differential sensitivities of these two responses suggested that the tissues mediating them might also be differentially sensitive to estradiol. In a previous paper, we showed that receptor translocation is an index of estrogen sensitivity. We measured receptor translocation in response to a series of estradiol doses in the POA/AH, the MBH, and the pituitary. Dose-response curves for estrogen's effect on receptor translocation showed that the pituitary receptor translocation mechanism is activated at significantly lower levels of serum estradiol than that of either the POA/AH or the MBH. These results are consistent with the POA/AH as a site of estrogen's positive feedback effects. In addition, they suggest that negative feedback in the rat may be mediated via estrogen's action at the anterior pituitary. Estrogen's negative feedback effect on serum LH occurs at a serum level of estrogen at which no receptor is translocated in the MBH. Therefore, the pituitary, which does possess nuclear receptors at these estradiol dose levels, is more likely to be the primary mediator of estrogen's negative feedback effects. In another experiment, pituitary, but not hypothalamic, receptor was translocated to the nuclear fraction with an injection of 100 micrograms clomiphere (Clomid). Under these conditions serum LH is depressed, thus strengthening the hypothesis that, in the rat, estrogen action on the pituitary can cause suppression of serum LH independently of the hormone's action in the hypothalamus.
在大鼠中，普遍认为雌激素对血清促黄体生成素（LH）产生刺激（正性）作用的主要部位是视前区 - 下丘脑前部（POA/AH）。相比之下，雌激素对血清LH水平产生抑制（负性）作用的主要部位尚未得到确凿认定。有证据表明，其作用部位既可能是下丘脑内侧基底部（MBH），也可能是垂体前叶。本研究利用了这些雌激素效应的一个独特特征来探究其假定的作用位点。雌激素诱导正反馈和负反馈的广泛剂量反应曲线表明，负反馈反应在血清雌二醇浓度低于正反馈反应时就被激活。这两种反应的不同敏感性表明，介导它们的组织对雌二醇的敏感性可能也存在差异。在之前的一篇论文中，我们表明受体易位是雌激素敏感性的一个指标。我们测量了POA/AH、MBH和垂体中一系列雌二醇剂量下的受体易位情况。雌激素对受体易位作用的剂量反应曲线表明，垂体受体易位机制在血清雌二醇水平显著低于POA/AH或MBH时被激活。这些结果与POA/AH作为雌激素正反馈作用的位点是一致的。此外，它们表明大鼠中的负反馈可能是通过雌激素在垂体前叶的作用介导的。雌激素对血清LH的负反馈作用发生在血清雌激素水平，此时MBH中没有受体易位。因此，在这些雌二醇剂量水平下确实拥有核受体的垂体，更有可能是雌激素负反馈作用的主要介导者。在另一项实验中，注射100微克克罗米酚（Clomid）后，垂体而非下丘脑的受体易位到核部分。在这些条件下血清LH降低，从而强化了这样一种假说，即在大鼠中，雌激素对垂体的作用可独立于其在下丘脑的作用而导致血清LH的抑制。
