GROWTH HORMONE REGULATION OF PUBERTY & FERTILITY

继续研究以确定生长激素(GH)是如何- 胰岛素样生长因子-I(IGF-I)轴在青少年中的调节 以及由此导致的生长激素和胰岛素样生长因子-I的变化如何影响 生殖成熟和成体生育能力。一种比较 摘除卵巢的青少年(n=11)至成年(n=11)女性 持续皮下注射胰岛素样生长因子-I有效地提高了 各年龄段血清主要载体蛋白(IGFBP-3)水平， 从而减缓给药肽的降解。雌二醇 替代治疗前青春期女性IGF-I分泌增加 青春期但实际上抑制了青春期后和 成年雌性。尽管老年人的生长激素分泌也减少了 女性，其下降不能解释其抑制作用 雌二醇对胰岛素样生长因子-I的影响相反，雌二醇会增加IGFBP-3的表达 年龄。这些数据表明，雌激素对肝脏的影响 IGF-I的分泌随生长发育而变化。 更多的研究表明，雌激素和生长激素状态相互作用 调节IGF-I轴。雌激素替代对这些女性的影响 降低血清IGF-I水平。尽管使用一种生长抑素进行治疗 类似物或生长激素受体拮抗剂显著降低血清 IGF-I，与雌二醇联合治疗均显著 血清IGF-I升高这些数据表明，生长激素状态决定了 雌二醇对肝脏IGF-I合成和释放的影响在……里面 另一项研究将IGF-I的作用与IGF-I类似物进行了比较 与不含NO的IGF-I载体蛋白的亲和力降低 在与IGF-I受体结合方面的妥协。胰岛素样生长因子-I输液 有效升高血清IGFBP-3，而类似物无此作用 效果。由于与受体的结合不会因 类似地，这些数据表明IGF-I可能通过减缓IGFBP-3的表达而增加IGFBP-3 载体蛋白的降解。功能研究表明， 长期输注IGF-I可促进猴的首次排卵(n =6)，并且这种效果与较早激活的 促黄体生成素释放激素(LHRH)神经元 动物对兴奋性氨基酸类似物的反应更快， N-甲基-D，L天冬氨酸高于未治疗女性(n=6)。然而， 这一效应依赖于相应的外源能力。 IGF-I升高血清IGFBP-3。如果IGFBP-3未显示 相应地，给药后IGF-I迅速降解，无法 有其特定于组织的效应。相比之下，成人的治疗 带有IGF-I(n=6)或生长抑素类似物(n=5)的猴子没有 影响排卵周期的参数。这些数据表明 生长激素-胰岛素样生长因子-I轴的影响可能仅限于青春期和 不参与维持正常排卵功能。

Studies were continued to determine how the growth hormone (GH) - insulin-like growth factor-I (IGF-I) axis is regulated in juveniles and adults and how resulting changes in GH and IGF-I affect reproductive maturation and adult fertility. A comparison of ovariectomized adolescent (n = 11) to adult (n = 11) females revealed that a constant subcutaneous infusion of IGF-I effectively elevated serum levels of its major carrier protein (IGFBP-3) at all ages, thereby slowing degradation of the administered peptide. Estradiol replacement augmented IGF-I secretion in adolescent females prior to puberty but actually suppressed serum IGF-I in post-adolescent and adult females. Although GH secretion was also diminished in the older females, its decrease could not account for the suppressive action of estradiol on IGF-I. In contrast, estradiol increased IGFBP-3 at all ages. These data suggest that the effect of estradiol on hepatic IGF-I secretion changes as a function of growth an d development. Additional studies indicated that estradiol and GH status interact to regulate the IGF-I axis. Estradiol replacement to these females decreased serum IGF-I. Although treatment with either a somatostatin analog or a GH receptor antagonist significantly decreased serum IGF-I, the combined treatment of either with estradiol significantly elevated serum IGF-I. These data suggest that GH status determines the effect of estradiol on hepatic IGF-I synthesis and release. In another study, the effects of IGF-I were compared to an IGF-I analog that has a reduced affinity for the IGF-I carrier proteins with no compromise in binding to the IGF-I receptor. IGF-I infusion effectively elevated serum IGFBP-3 whereas the analog had no such effect. Since binding to the receptor is not compromised with the analog, these data suggest that IGF-I may increase IGFBP-3 by slowing degradation of the carrier protein. Functional studies revealed that the chronic infusion with IGF-I advances first ovulation in monkeys (n = 6) and this effect is associated with an earlier activation of luteinizing hormone releasing hormone (LHRH) neurons as treated animals were more responsive to the excitatory amino acid analog, n-methyl d,l aspartic acid than untreated females (n = 6). However, this effect is dependent upon the corresponding ability of exogenous IGF-I to elevate serum IGFBP-3. If IGFBP-3 does not show a corresponding rise, administered IGF-I is quickly degraded, unable to have its tissue specific effects. In contrast, treatment of adult monkeys with IGF-I (n = 6) or a somatostatin analog (n = 5) did not affect the parameters of an ovulatory cycle. These data suggest that the effects of the GH - IGF-I axis may be limited to puberty and are not involved in the maintenance of normal ovulatory function.