Clark Ann S, Kelton Megan C, Whitney Andrew C
Department of Psychological and Brain Sciences, Dartmouth College, Hanover, New Hampshire 03755, USA.
Biol Reprod. 2003 Feb;68(2):465-71. doi: 10.1095/biolreprod.102.008078.
Use of anabolic-androgenic steroids (AASs) is becoming increasingly popular among adolescent girls, yet the effects of AASs on female physiology and development are not well understood. The present study compared the effects of chronic exposure to three individual AASs, stanozolol (0.05-5 mg/kg), 17alpha-methyltestosterone (0.5-5 mg/kg), and methandrostenolone (0.5-5 mg/kg) on the onset of puberty and estrous cyclicity in the rat. Female rats received daily injections of AASs for 30 days (Postnatal Day [PN] 21-51). Rats receiving the highest dose of each of the AASs (5 mg/kg) displayed vaginal opening at a younger age than rats receiving the oil vehicle. The day of first vaginal estrus was delayed in rats receiving stanozolol (5 mg/kg) or 17alpha-methyltestosterone (0.5-5 mg/kg) but not in rats receiving methandrostenolone. At the highest dose (5 mg/kg), each of the AASs reduced the incidence of regular estrous cyclicity during the treatment period. Concurrent administration (on PN21-51) of the androgen receptor antagonist, flutamide (10 mg/kg, twice daily), reversed the effects of 17alpha-methyltestosterone (5 mg/kg) on vaginal opening. Flutamide administration also eliminated the effects of stanozolol (5 mg/kg) and 17alpha-methyltestosterone (5 mg/kg) on the day of first vaginal estrus. In contrast, rats receiving flutamide and methandrostenolone (5 mg/kg) exhibited first vaginal estrus earlier than controls. The present results indicate that chronic exposure to AASs during development has deleterious effects on the female neuroendocrine axis and that these effects appear be mediated via multiple mechanisms.
合成代谢雄激素类固醇（AASs）在青春期女孩中的使用正变得越来越普遍，然而AASs对女性生理和发育的影响尚未得到充分了解。本研究比较了长期暴露于三种单独的AASs，即司坦唑醇（0.05 - 5毫克/千克）、17α-甲基睾酮（0.5 - 5毫克/千克）和大力补（0.5 - 5毫克/千克）对大鼠青春期启动和发情周期的影响。雌性大鼠每天注射AASs，持续30天（出生后第[PN]21 - 51天）。接受每种AASs最高剂量（5毫克/千克）的大鼠比接受油载体的大鼠阴道开口年龄更小。接受司坦唑醇（5毫克/千克）或17α-甲基睾酮（0.5 - 5毫克/千克）的大鼠首次阴道发情日延迟，但接受大力补的大鼠没有延迟。在最高剂量（5毫克/千克）时，每种AASs在治疗期间都降低了规律发情周期的发生率。同时给予雄激素受体拮抗剂氟他胺（10毫克/千克，每日两次）（在PN21 - 51期间）可逆转17α-甲基睾酮（5毫克/千克）对阴道开口的影响。氟他胺给药还消除了司坦唑醇（5毫克/千克）和17α-甲基睾酮（5毫克/千克）对首次阴道发情日的影响。相比之下，接受氟他胺和大力补（5毫克/千克）的大鼠首次阴道发情比对照组更早。目前的结果表明，发育过程中慢性暴露于AASs对女性神经内分泌轴有有害影响，并且这些影响似乎是通过多种机制介导的。
