Bellantoni M F, Harman S M, Cho D E, Blackman M R
Endocrinology Section, National Institute on Aging, National Institutes of Health, Francis Scott Key Medical Center, Baltimore, Maryland 21224.
J Clin Endocrinol Metab. 1991 Jan;72(1):172-8. doi: 10.1210/jcem-72-1-172.
Prior studies in women have shown a positive correlation of endogenous estrogen levels with spontaneous and stimulated GH secretion and basal insulin-like growth factor-I (IGF-I) levels. In postmenopausal women, estrogen replacement therapy (ERT) by the oral route increases basal and GHRH-stimulated GH secretion but decreases basal IGF-I levels. To assess the corresponding effects of transdermal ERT (tERT) on this axis, we administered four 8-week regimens of transdermal 17 beta-estradiol (Estraderm; 0, 50, 100, or 150 micrograms/day) combined with oral medroxyprogesterone acetate (10 mg each day) during weeks 3-4 and 7-8 of each 8-week regimen (except placebo) to 28 healthy nonobese postmenopausal women, aged 45.3-71.8 yr. Basal levels of estradiol (E2), GH, and IGF-I as well as GH responsivity to bolus iv administration of GH-releasing hormone-(1-44) (1 micrograms/kg), were measured before tERT and at weeks 6 and 8 of each regimen; estrone (E1) levels were measured before tERT and at week 6 of each regimen. Before tERT, age was inversely correlated with both the peak GH response to GHRH (r = -0.43; P less than 0.02) and basal IGF-I levels (r = -0.37; P less than 0.05), but not with basal E2, E1, or GH levels. There were progressive increases in plasma E2 and E1 levels with increasing doses of tERT (P = 0.0001), independent of age (P greater than 0.2) and body mass index (P greater than 0.2). Mean basal GH and IGF-I levels were not altered significantly by tERT or medroxyprogesterone acetate. Peak and integrated GH secretory responses to exogenous GHRH decreased with increasing tERT dose (P less than 0.01) in both younger and older postmenopausal women. Our findings suggest that the known effects of tERT on bone and other tissues are not mediated via increases in circulating levels of immunoreactive GH or IGF-I, but do not preclude the possibility of tERT-induced increases in the biological activity or paracrine action of IGF-I.
先前针对女性的研究表明，内源性雌激素水平与自发性及刺激性生长激素（GH）分泌以及基础胰岛素样生长因子-I（IGF-I）水平呈正相关。在绝经后女性中，口服途径的雌激素替代疗法（ERT）可增加基础及生长激素释放激素（GHRH）刺激的GH分泌，但会降低基础IGF-I水平。为评估经皮ERT（tERT）对该轴的相应影响，我们在28名年龄在45.3 - 71.8岁的健康非肥胖绝经后女性的每个8周疗程（安慰剂除外）的第3 - 4周和第7 - 8周，给予四种为期8周的经皮17β-雌二醇（Estraderm；0、50、100或150微克/天）与口服醋酸甲羟孕酮（每天10毫克）联合治疗方案。在tERT治疗前以及每个疗程的第6周和第8周，测量雌二醇（E2）、GH和IGF-I的基础水平以及静脉推注GH释放激素-（1 - 44）（1微克/千克）后GH的反应性；在tERT治疗前以及每个疗程的第6周测量雌酮（E1）水平。在tERT治疗前，年龄与对GHRH的GH峰值反应（r = -0.43；P < 0.02）和基础IGF-I水平（r = -0.37；P < 0.05）均呈负相关，但与基础E2、E1或GH水平无关。随着tERT剂量增加，血浆E2和E1水平逐渐升高（P = 0.0001），与年龄（P > 0.2）和体重指数（P > 0.2）无关。tERT或醋酸甲羟孕酮对基础GH和IGF-I平均水平无显著影响。在年轻和老年绝经后女性中，随着tERT剂量增加，对外源性GHRH的GH峰值和整体分泌反应均降低（P < 0.01）。我们的研究结果表明，tERT对骨骼和其他组织的已知作用并非通过循环中免疫反应性GH或IGF-I水平的升高介导，但并不排除tERT诱导IGF-I生物活性或旁分泌作用增加的可能性。
