GROWTH HORMONE REGULATION OF PUBERTY & FERTILITY

研究继续确定如何生长激素（GH）- 胰岛素样生长因子-I（IGF-I）轴在青少年中受到调节 以及GH和IGF-I的变化如何影响 生殖成熟和成年生育力。 的比较 卵巢切除的青少年（n = 11）至成年（n = 11）女性显示 持续皮下注射IGF-I有效地提高了 其主要载体蛋白（IGFBP-3）在所有年龄的血清水平， 从而减缓所施用的肽的降解。 雌二醇 替代治疗增加了青春期女性的IGF-I分泌， 青春期，但实际上抑制血清IGF-I在青春期后， 成年女性 尽管老年人的GH分泌也减少， 女性，其减少不能解释的抑制作用 雌二醇对IGF-I的影响。 与此相反，雌二醇增加IGFBP-3在所有 年龄 这些数据表明，雌二醇对肝脏的影响， IGF-I的分泌随着生长发育而变化。 其他研究表明，雌二醇和生长激素状态相互作用， 调节IGF-I轴。 这些雌性的替代品 降低血清IGF-I。 虽然用生长抑素治疗 类似物或GH受体拮抗剂显著降低血清 IGF-I与雌二醇联合治疗， 血清IGF-I升高。 这些数据表明，GH状态决定 雌二醇对肝脏IGF-I合成和释放的影响。 在 在另一项研究中，将IGF-I的作用与IGF-I类似物进行了比较 其对IGF-I载体蛋白的亲和力降低， 与IGF-I受体结合的妥协。 IGF-I输注 有效地升高血清IGFBP-3，而类似物没有这样的作用。 效果 由于与受体的结合不受蛋白质的影响， 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可提前猴的首次排卵（n = 6），这种效应与早期激活 促黄体激素释放激素（LHRH）神经元 动物对兴奋性氨基酸类似物更敏感， N-甲基D，L-天冬氨酸比未处理的雌性（n = 6）。 然而，在这方面， 这种效应依赖于外源性的相应能力， IGF-I升高血清IGFBP-3。 如果IGFBP-3不显示 当IGF-I相应升高时，给予的IGF-I迅速降解，不能 具有组织特异性作用。 与此相反，成人治疗 用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 GH-IGF-I轴的作用可能仅限于青春期， 不参与维持正常的排卵功能。

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.