Billiar R B, Richardson D, Anderson E, Mahajan D, Little B
Endocrinology. 1985 Jun;116(6):2209-20. doi: 10.1210/endo-116-6-2209.
The concept that chronically elevated blood androstenedione concentrations increase the incidence of anovulation in the primate and that acyclic elevated basal blood androgen and/or estrogen concentrations cause abnormal gonadotropin secretion was studied. Regularly menstruating female rhesus monkeys were implanted sc with Silastic tubing filled with androstenedione or estrone and compared with controls. Androstenedione implants increased the serum androstenedione concentrations from 1.6 +/- 0.1 (SE) ng/ml to 6.30 +/- 0.27 ng/ml. By peripheral conversion the testosterone concentration increased from control values of 279 +/- 10 (SE) pg/ml to 1280 +/- 41 pg/ml. The testosterone concentration in the estrone-treated monkeys was 247 +/- 9.7 pg/ml. The estrone concentrations were: controls, 63.2 +/- 3.1 (SE) pg/ml; androstenedione-treated monkeys, 63.2 +/- 3.1 pg/ml; and estrone-treated animals, 150 +/- 5.3 pg/ml. The corresponding estradiol concentrations were: control animals, 35.1 +/- 2.1 (SE) pg/ml; androstenedione animals, 30.9 +/- 1.8 pg/ml; and estrone-treated monkeys, 65.7 +/- 3.9 pg/ml. There was no difference in the morning serum cortisol concentrations between any of the three groups or between ovulatory or anovulatory months. The chronic elevation of either androstenedione or estrone caused an increased incidence of anovulation compared with the controls. Increased estrogen concentrations caused increased anovulation during both summer and winter months; however, increased androgen concentrations caused increased anovulation only during the summer months. However, LH concentrations were unaffected in either group but were lower during anovulation months in all three groups. An LH or FSH surge followed an estradiol bolus in three of four control animals and four of six androstenedione-treated but none of the estrone-treated monkeys. Histological examination of ovarian biopsies demonstrated thickening of the tunica albuginea ovarii in androgen-treated ovaries and an apparent increased number of atretic follicles. Corpora lutea were absent in the ovaries of the estrogen-treated monkeys, but otherwise these ovaries were similar to those of controls. It is concluded that chronic acyclic elevation of blood androstenedione (and resultant testosterone) increases seasonal anovulation in the rhesus monkey. Increased blood estrone (and resultant estradiol) leads to almost complete anovulation throughout the year and renders the central nervous system-pituitary axis insensitive to positive feedback effect of estradiol. Neither treatment caused an increase in basal LH concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)
研究了长期升高的血液雄烯二酮浓度会增加灵长类动物无排卵发生率,以及无周期的基础血液雄激素和/或雌激素浓度升高会导致促性腺激素分泌异常这一概念。将装有雄烯二酮或雌酮的硅橡胶管皮下植入规律月经的雌性恒河猴体内,并与对照组进行比较。雄烯二酮植入使血清雄烯二酮浓度从1.6±0.1(标准误)ng/ml升高至6.30±0.27 ng/ml。通过外周转化,睾酮浓度从对照组的279±10(标准误)pg/ml升高至1280±41 pg/ml。雌酮处理的猴子中睾酮浓度为247±9.7 pg/ml。雌酮浓度分别为:对照组63.2±3.1(标准误)pg/ml;雄烯二酮处理的猴子63.2±3.1 pg/ml;雌酮处理的动物150±5.3 pg/ml。相应的雌二醇浓度分别为:对照动物35.1±2.1(标准误)pg/ml;雄烯二酮处理的动物30.9±1.8 pg/ml;雌酮处理的猴子65.7±3.9 pg/ml。三组中的任何一组之间以及排卵或不排卵月份之间,早晨血清皮质醇浓度均无差异。与对照组相比,雄烯二酮或雌酮的慢性升高均导致无排卵发生率增加。雌激素浓度升高在夏季和冬季均导致无排卵增加;然而,雄激素浓度升高仅在夏季导致无排卵增加。然而,两组的促黄体生成素(LH)浓度均未受影响,但在所有三组的无排卵月份中均较低。在四只对照动物中的三只以及六只雄烯二酮处理的动物中的四只中,雌二醇推注后出现LH或促卵泡生成素(FSH)高峰,但雌酮处理的猴子中无一出现。卵巢活检的组织学检查显示,雄激素处理的卵巢中白膜增厚,闭锁卵泡数量明显增加。雌酮处理的猴子卵巢中无黄体,但除此之外,这些卵巢与对照组相似。得出结论,血液雄烯二酮(及由此产生的睾酮)的慢性无周期升高会增加恒河猴的季节性无排卵。血液雌酮(及由此产生的雌二醇)升高导致全年几乎完全无排卵,并使中枢神经系统-垂体轴对雌二醇的正反馈作用不敏感。两种处理均未导致基础LH浓度升高。(摘要截短至400字)