Kowalski W, Chatterton R T
Department of Obstetrics and Gynecology, Northwestern University Medical School, Chicago, Illinois 60611.
Fertil Steril. 1992 Apr;57(4):912-20.
To assess the impact of elevated adrenal androgen levels on ovarian function in a nonhuman primate using a repeated measures experimental design.
Osmotic pumps that released dehydroepiandrosterone sulfate (DHEAS) were implanted subcutaneously in five cynomolgus monkeys (Macaca fascicularis) for one menstrual cycle. The pumps were filled with saline for the two control cycles, one preceding and the other following DHEAS infusion.
Administration of DHEAS elevated its levels in serum fourfold and in urine sevenfold, which returned to pretreatment values in the next cycle. Serum concentrations of estradiol (E2) were reduced by 55% during DHEAS administration in both follicular and luteal phases and were still decreased in the following cycle by 69% in follicular phase and 48% in luteal phase (P less than 0.01). Luteal serum progesterone (P) levels were diminished by 52% during treatment and were accompanied by 56% reduction in immunoreactive pregnanediol excretion in urine (P less than 0.05). Serum luteinizing hormone (LH) levels were decreased during DHEAS infusion by 51% in follicular phase and 58% in luteal phase (P less than 0.01) but returned to baseline in the next cycle. Conversely, serum follicle-stimulating hormone (FSH) concentrations were increased during treatment by 70% in follicular phase and 101% in luteal phase and remained increased by 58% in follicular phase of the next cycle (P less than 0.05). Estrone excretion in urine was higher during DHEAS infusion (1.5-fold increase) but was below pretreatment values in the following cycle by 57% in follicular phase and 51% in luteal phase (P less than 0.001). Administration of DHEAS did not change significantly serum levels of sex hormone-binding globulin. The length of menstrual cycles was not affected by increased levels of adrenal androgens either. However, in the cycles that followed DHEAS infusion, follicular phase was prolonged by an average of 9 days, and luteal phase was shortened by an average of 5 days (P less than 0.01).
These data document that subchronically elevated adrenal androgen levels in primates: (1) suppress E2 and P levels, which may affect fertility; (2) differentially affect gonadotropin secretion, decreasing LH and increasing FSH serum concentrations; and (3) result in disturbances of ovarian function that persist for at least one menstrual cycle after normalization of androgen levels.
采用重复测量实验设计，评估肾上腺雄激素水平升高对非人灵长类动物卵巢功能的影响。
将释放硫酸脱氢表雄酮（DHEAS）的渗透泵皮下植入5只食蟹猴（猕猴）体内，持续一个月经周期。在DHEAS输注前和输注后的两个对照周期，泵内填充生理盐水。
给予DHEAS后，血清中DHEAS水平升高4倍，尿液中升高7倍，在下一个周期恢复到治疗前水平。在卵泡期和黄体期给予DHEAS期间，血清雌二醇（E2）浓度降低55%，在下一个周期的卵泡期仍降低69%，黄体期降低48%（P<0.01）。治疗期间黄体期血清孕酮（P）水平降低52%，同时尿中免疫反应性孕二醇排泄减少56%（P<0.05）。在DHEAS输注期间，卵泡期血清促黄体生成素（LH）水平降低51%，黄体期降低58%（P<0.01），但在下一个周期恢复到基线水平。相反，治疗期间卵泡期血清促卵泡生成素（FSH）浓度升高70%，黄体期升高101%，在下一个周期的卵泡期仍升高58%（P<0.05）。DHEAS输注期间尿中雌酮排泄增加（增加1.5倍），但在下一个周期的卵泡期低于治疗前水平57%，黄体期低于51%（P<0.001）。给予DHEAS对血清性激素结合球蛋白水平无显著影响。月经周期长度也不受肾上腺雄激素水平升高的影响。然而，在DHEAS输注后的周期中，卵泡期平均延长9天，黄体期平均缩短5天（P<0.01）。
这些数据表明，灵长类动物肾上腺雄激素水平亚慢性升高：（1）抑制E2和P水平，这可能影响生育能力；（2）对促性腺激素分泌有不同影响，降低LH水平，增加FSH血清浓度；（3）导致卵巢功能紊乱，在雄激素水平恢复正常后至少持续一个月经周期。
