GROWTH HORMONE REGULATION OF PUBERTY & FERTILITY

这些正在进行的研究继续检验工作假说 生长激素诱导的胰岛素样生长因子-I的增加 胰岛素样生长因子-I(IGF-I)调节成人青春期的节奏并促进生育 女性。用于管理的IGF-I由 基因泰克公司和生长抑素类似物奥曲肽 由Sandoz制药公司慷慨提供。主要发现包括 1)IGF-I促进女性青春期发育 猴子，提前第一次排卵的年龄；2)IGF-I管理 增强垂体对黄体生成素(LH)分泌的反应 对兴奋性氨基酸类似物，绝经后女性的NMDA； 3)既不补充IGF-I，也不使用生长抑素治疗 类似物(降低内源性IGF-I)影响的参数 成年女性的排卵周期；4)既不补充IGF-I 生长抑素类似物的NOR治疗会影响脑垂体 促黄体生成素分泌对促黄体生成素释放激素类似物的反应 青春期后或成年女性；5)IGF-I增加血清 浓度的IGFBP-3，通过以下方式有效地提高其生物活性 减慢退化速度。这些数据表明，外设在 胰岛素样生长因子-I和胰岛素样生长因子结合蛋白-3在女性青春期调节中起重要作用 但并不参与维持成人的生育能力。 资助NIH/NICHD$87,692 4/01/82-11/30/98出版物， M.E.对生长激素-胰岛素样生长因子-I的调节 雌二醇对发育期和成年猴的胰岛素样生长因子-I轴的影响 用IGF-I替代和补充。J.of Clin.内分泌激素。 梅塔布。83：2018-2028,1998。威尔逊，M.E.过早抬高 胰岛素样生长因子-I促进恒河猴首次排卵 猴子。J.内分泌。158：247-257,1998。威尔逊，M.E.的影响 雌二醇和外源性胰岛素样生长因子-I对血管内皮细胞的影响 胰岛素样生长因子-I轴在生长激素抑制和拮抗临床应用中的作用。 内分泌激素。梅塔布。83：4013-4021,1998。威尔逊，M.E.连续 皮下输液而不是每天两次注射 胰岛素样生长因子-I更有效地提高血清胰岛素样生长因子水平 雌性猕猴体内的结合(IGFBP)-3。欧元。J.内分泌。(在 按下)。Wilson，M.E.和Lackey，S.IGF-I，但不是IGF-I变体 Long R3 IGF-I增加青春期猕猴血清IGFBP-3。生长 激素和胰岛素样生长因子研究(在印中)。P51 RR00165-38 1/1/98-12/31/98 耶尔基斯地区灵长类研究中心

These ongoing studies continued to test the working hypothesis that growth hormone-induced increases in insulin-like growth factor-I (IGF-I) regulates the tempo of puberty and promotes fertility in adult females. IGF-I for administration was generously provided by Genentech Inc. and the somatostatin analogue, Octreotide, was generously provided by Sandoz Pharmaceuticals. Major findings include 1) IGF-I administration accelerates the tempo of puberty in female monkeys, advancing the age at 1st ovulation; 2) IGF-I administration enhanced the pituitary response in luteinizing hormone (LH) secretion to the excitatory amino acid analog, NMDA in post menarchial females; 3) neither IGF-I supplementation nor treatment with a somatostatin analogue (which lowers endogenous IGF-I) affected parameters of ovulatory cycles in adult females; 4) neither IGF-I supplementation nor treatment with a somatostatin analogue affected the pituitary response in LH secretion to an LH re leasing hormone analog in post-pubertal or adult females; 5) IGF-I increases serum concentrations of IGFBP-3, effectively increasing its bioactivity by slowing degradation. These data indicate that peripheral increases in IGF-I and IGFBP-3 play an important role regulating puberty in females but is not involved in the maintenance of fertility in adults. FUNDING NIH / NICHD $87,692 4/01/82 - 11/30/98 PUBLICATIONS Wilson, M.E. Regulation of the growth hormone - insulin-like growth factor-I (IGF-I) axis in developing and adult monkeys is affected by estradiol replacement and supplementation with IGF-I. J. of Clin. Endocrinol. Metab. 83:2018-2028, 1998. Wilson, M.E. Premature elevation in insulin-like growth factor-I advances first ovulation in rhesus monkeys. J. Endocrinol. 158:247-257, 1998. Wilson, M.E. Effects of estradiol and exogenous insulin-like growth factor (IGF) -I on the IGF-I axis during GH inhibition and antagonism J. of Clin. Endocrinol. Metab. 83:4013-4021, 1998. Wilson, M.E. Continuous subcutaneous infusion rather than twice daily injections of insulin-like growth (IGF) -I more effectively elevates serum IGF binding (IGFBP) -3 in female monkeys. Eur. J. Endocrinol. (In press). Wilson, M.E. and Lackey, S. IGF-I but not the IGF-I variant Long R3 IGF-I increases serum IGFBP-3 in adolescent monkeys. Growth Hormone & IGF Res. (In press). P51 RR00165-38 1/1/98 - 12/31/98 Yerkes Regional Primate Research Center