Nass T E, Matt D W, Judd H L, Lu J K
Biol Reprod. 1984 Nov;31(4):723-31. doi: 10.1095/biolreprod31.4.723.
To examine the effects of prepubertal steroid environment on subsequent estrous cyclicity and gonadotropin secretion, Silastic implants containing 25, 50 or 100% 17 beta-estradiol (E2;n=34), 50% diethylstilbestrol (DES; n=16) or 50% testosterone (T; n=17) were placed into female rats at 12 days of age and removed on the day of vaginal opening (18-24 days of age). At 80 days of age, the percentages of regularly cycling females in the E2-(three groups combined), DES- and T-implanted groups were 59%, 0% and 59%, respectively. By 110 days of age, the percentages were reduced to 24%, 0% and 0%, and at 140 days of age 6%, 0% and 0%, respectively. Many of these females displayed irregular estrous cycles followed by a persistent estrous (PE) state. By contrast, 89% of the control females (blank implants or no implant) maintained regular cycles up to 140 days of age. At 150 days of age, an i.p. injection of gonadotropin-releasing hormone (GnRH; 100 ng/100 g BW) markedly increased serum luteinizing hormone (LH), but not follicle-stimulating hormone (FSH), in intact PE females treated prepubertally with E2 implants. After the test with GnRH, PE rats were ovariectomized (OVX). Thirty days after OVX, similar GnRH administration significantly increased serum levels of both LH and FSH, but these responses were significantly (P less than 0.01) reduced when compared with those in OVX controls. Progesterone administration to estradiol benzoate-primed, acutely (3 days) OVX, or long-term (43 days) OVX-PE females did not increase LH or FSH release. These results indicate that exposure to exogenous estrogen or T prior to puberty precipitates the decline in estrous cyclicity associated with the loss of gonadotropin surge response, presumably due to an alteration in hypothalamic GnRH release.
为研究青春期前类固醇环境对随后发情周期和促性腺激素分泌的影响，在12日龄雌性大鼠体内植入含25%、50%或100% 17β-雌二醇（E2；n = 34）、50%己烯雌酚（DES；n = 16）或50%睾酮（T；n = 17）的硅橡胶植入物，并在阴道开口日（18 - 24日龄）取出。80日龄时，E2植入组（三组合并）、DES植入组和T植入组中规律发情雌性大鼠的百分比分别为59%、0%和59%。到110日龄时，这些百分比分别降至24%、0%和0%，140日龄时分别为6%、0%和0%。许多此类雌性大鼠表现出发情周期不规律，随后进入持续发情（PE）状态。相比之下，89%的对照雌性大鼠（植入空白植入物或未植入）在140日龄前维持规律周期。150日龄时，腹腔注射促性腺激素释放激素（GnRH；100 ng/100 g体重）可使青春期前接受E2植入物处理的完整PE雌性大鼠血清黄体生成素（LH）显著升高，但对促卵泡激素（FSH）无影响。GnRH检测后，对PE大鼠进行卵巢切除（OVX）。OVX 30天后，类似的GnRH给药可显著提高血清LH和FSH水平，但与OVX对照组相比，这些反应显著降低（P < 0.01）。对苯甲酸雌二醇预处理的急性（3天）OVX或长期（43天）OVX - PE雌性大鼠给予孕酮，并未增加LH或FSH释放。这些结果表明，青春期前暴露于外源性雌激素或睾酮会导致发情周期下降，并伴有促性腺激素激增反应丧失，推测这是由于下丘脑GnRH释放改变所致。
