Cheung C Y, Davidson J M
Endocrinology. 1977 Feb;100(2):292-302. doi: 10.1210/endo-100-2-292.
The effects of intrahypothalamic and subcutaneous implants of testosterone (T) and those of hypothalamic lesions on resting levels of circulating LH and pituitary responsiveness to exogenous LHRH were studied in castrated male rats to elucidate hypothalamic and pituitary regulation of LH secretion. Two hundred mug implants of testosterone propionate (TP) in the median eminence region suppressed plasma LH titers before evidence of direct inhibition of pituitary function (as indicated by testing with LHRH) was found. Such implants release appreciable amounts of T into the peripheral circulation in the immediate post-operative period, and SC Silastic (constant release) capsules containing T have similar effects. The findings suggest that, regardless of the site of implant, the initial negative feedback inhibition of LH by T is not dependent on direct action at the pituitary levels but rather appears to be a hypothalamic effect. In the days following exposure to hypothalamic or peripheral implantation of T, however, a progressively developing decline in the response to exogenous LHRH was observed. In order to determine whether this effect results from suppression of endogenous LHRH release, the median eminence-arcuate region was destroyed to remove the source of LHRH. In these animals, the suppression of plasma LH was evident on the first day after the lesion, but pituitary responsiveness to LHRH was unaffected until after one week. When Sialastic capsules were implanted SC into lesioned animals, a more rapid (less than 1 week) inhibition of pituitary responsivity ensued. Suprachiasmatic lesions did not affect basal LH secretion or pituitary responses to LHRH. The data provide evidence for a dual feedback action of T on LH in castrated male rats: an initial inhibitory effect presumably due to hypothalamic inhibition (commencing at around 6h after hypothalamic of SC implantation of T), and a subsequent suppression of pituitary responisveness (after one day) presumably due to direct action of T on the pituitary. In addition to these phenomena, findings in rats bearing median eminence-arcurate lesions suggest that the removal of endogenous LHRH by itself leads to an eventual decline in pituitary responsiveness (greater than one week postoperatively).
为阐明下丘脑和垂体对促黄体生成素（LH）分泌的调节作用，研究了在去势雄性大鼠中下丘脑内和皮下植入睾酮（T）的效果以及下丘脑损伤对循环LH的静息水平和垂体对外源性促性腺激素释放激素（LHRH）反应性的影响。在正中隆起区域植入200微克丙酸睾酮（TP），在发现垂体功能受到直接抑制的证据（通过LHRH测试表明）之前，血浆LH滴度就已被抑制。这种植入物在术后即刻会将相当数量的T释放到外周循环中，而含有T的皮下硅橡胶（持续释放）胶囊也有类似效果。这些发现表明，无论植入部位如何，T对LH的初始负反馈抑制并不依赖于对垂体水平的直接作用，而似乎是一种下丘脑效应。然而，在暴露于下丘脑或外周植入T后的几天里，观察到对外源性LHRH的反应逐渐下降。为了确定这种效应是否源于内源性LHRH释放的抑制，破坏了正中隆起 - 弓状核区域以去除LHRH的来源。在这些动物中，损伤后第一天血浆LH的抑制就很明显，但垂体对LHRH的反应性直到一周后才受到影响。当将硅橡胶胶囊皮下植入损伤动物时，垂体反应性的抑制更快（不到1周）。视交叉上核损伤不影响基础LH分泌或垂体对LHRH的反应。这些数据为去势雄性大鼠中T对LH的双重反馈作用提供了证据：最初的抑制作用可能是由于下丘脑抑制（在下丘脑或皮下植入T后约6小时开始），随后垂体反应性的抑制（一天后）可能是由于T对垂体的直接作用。除了这些现象外，在有正中隆起 - 弓状核损伤的大鼠中的发现表明，内源性LHRH的去除本身会导致垂体反应性最终下降（术后大于一周）。
