Brawer J R, Naftolin F, Martin J, Sonnenschein C
Endocrinology. 1978 Aug;103(2):501-12. doi: 10.1210/endo-103-2-501.
Young adult cyclic female rats were each injected with 2 mg estradiol valerate (EV) in sesame oil. Controls received an equivalent volume of sesame oil. Within 2 months after injection, most of the EV-treated animals showed persistent vaginal estrus and small polyfollicular ovaries as well as pathological changes in the hypothalamic arcuate nucleus. This pathological process was gradually progressive such that by 6 months after EV injection, the basal lateral region of the nucleus contained numerous reactive microglia, astrocytes, and degenerating elements of the neuropil. The experimental rats had elevated plasma PRL and GH concentrations which gradually diminished. Plasma estradiol concentration remained elevated 2 months after injection, while plasma LH and FSH concentrations stayed within the high and low normal range, respectively. The pituitary glands of injected animals weighed significantly more than those of controls 5.5 months after injection, but the enlarged glands did not cause hypothalamic compression. As mechanical anterior deafferentation of the medial basal hypothalamus has previously been shown to produce similar endocrine and reproductive alterations, it may be that estradiol treatment results in a functional-anatomical disconnection of the arcuate nucleus from the more anterior hypothalamic areas that regulate cyclicity. Whether this type of functional-anatomical phenomenon underlies other varieties of induced or secondary acyclicity in females remains to be determined.
将年轻成年雌性周期大鼠每只注射2毫克戊酸雌二醇（EV）的芝麻油溶液。对照组注射等量的芝麻油。注射后2个月内，大多数接受EV治疗的动物出现持续性阴道发情、多囊性小卵巢以及下丘脑弓状核的病理变化。这种病理过程是逐渐进展的，以至于在注射EV后6个月，该核的基底外侧区域含有大量反应性小胶质细胞、星形胶质细胞和神经纤维网的退化成分。实验大鼠的血浆催乳素（PRL）和生长激素（GH）浓度升高，随后逐渐降低。注射后2个月血浆雌二醇浓度仍保持升高，而血浆促黄体生成素（LH）和促卵泡生成素（FSH）浓度分别保持在正常范围的高值和低值。注射后5.5个月，注射动物的垂体重量明显高于对照组，但增大的垂体并未导致下丘脑受压。由于先前已证明对下丘脑内侧基部进行机械性前路去传入神经会产生类似的内分泌和生殖改变，因此可能是雌二醇治疗导致弓状核与调节周期性的下丘脑前部区域出现功能-解剖学上的分离。这种类型的功能-解剖学现象是否是女性其他类型的诱导性或继发性无周期性的基础，仍有待确定。
