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• W2086448758 abstract "Developmental changes in the GH-insulin-like growth factor I (IGF-I) axis were evaluated in female rhesus monkeys to test the hypothesis that estradiol differentially regulates IGF-I secretion and molar ratios of IGF-I to IGF-binding protein-3 (IGFBP-3) from adolescence into adulthood and that estradiol can reestablish GH secretion in the face of enhanced IGF-I negative feedback inhibition of GH. Adult ovariectomized females were compared to ovariectomized adolescent females studied from 18–36 months of age, a period encompassing the juvenile phase through the expected age at first ovulation. A subgroup of adult (n = 5) and adolescent females (n = 5) was treated continuously with human IGF-I (110 μg/kg·day, sc) throughout the study period and were compared to age-matched, untreated adults (n= 5) and adolescent animals (n = 6). To further understand how IGF-I affects the GH-IGF-I axis, the acute response to IGF-I (100μ g/kg, sc) was assessed in adults and at two ages in developing females. Furthermore, all females were treated periodically with estradiol (4 μg/kg·day) to assess the effects on the parameters of the GH-IGF-I axis from adolescence into adulthood. Finally, the response to GHRH (1.0 μg/kg, iv) was assessed in adult females and in adolescent females at 18 and 24 months during no estradiol and estradiol replacement. Serum IGF-I and IGFBP-3, in the absence of estradiol replacement, increased significantly throughout puberty before declining from late adolescence into adulthood. Supplementation with IGF-I resulted in a significant increase in both serum IGF-I and IGFBP-3 concentrations at all ages, although the effect was less in juvenile females. Nevertheless, the age-dependent increase and decline in IGF-I and IGFBP-3 were maintained in these supplemented animals. Estradiol replacement significantly increased both serum IGF-I and IGFBP-3 through adolescence, even in IGF-I-supplemented animals. However, with the transition from adolescence, estradiol suppressed serum IGF-I secretion, yet continued to increase IGFBP-3 in young adult and fully adult females. This change in proportionately less IGF-I compared with IGFBP-3 resulted in a significant age-dependent decrease in the molar ratio of IGF-I to IGFBP-3. Indeed, the molar ratio was highest during midadolescence, when both IGF-I and IGFBP-3 were at their zeniths. Serum IGFBP-1 was significantly higher in adolescent compared with adult females. However, estradiol replacement significantly elevated serum IGFBP-1 in adult, but not adolescent, females, abolishing the age differences observed under no estradiol conditions. Serum GH was significantly higher in adolescent compared with adult females; levels in juvenile animals were intermediate. Replacement with estradiol significantly elevated serum GH in adolescent and adult females, particularly in females supplemented with IGF-I. In contrast, estradiol had no effect on serum GH during the juvenile phase. Supplementation with IGF-I significantly dampened the response to GHRH in young and fully adult females, but not in juvenile animals. However, estradiol replacement restored the response to GHRH in these adult, IGF-I-supplemented females. These data indicate that in the absence of any ovarian influence, the decline in serum IGF-I and IGFBP-3 begins in postpubertal, young adult females and is not necessarily a consequence of old age. Furthermore, there is an age-dependent uncoupling of estradiol regulation of the GH-IGF-I axis, as estradiol stimulates GH and IGFBP-3 at all ages but increases serum IGF-I only during adolescent and decreases IGF-I in postpubertal, young adult females. Furthermore, IGF-I has a greater suppressive effect on GH secretion with advancing age, an effect reversed by estradiol replacement. These data suggest that the deficits in the GH-IGF-I axis observed in aged individuals may reflect a continuation of the regulatory changes that begin in young adult females." @default.
• W2086448758 created "2016-06-24" @default.
• W2086448758 creator A5071603430 @default.
• W2086448758 date "1998-06-01" @default.
• W2086448758 modified "2023-10-16" @default.
• W2086448758 title "Regulation of the Growth Hormone-Insulin-Like Growth Factor I Axis in Developing and Adult Monkeys Is Affected by Estradiol Replacement and Supplementation with Insulin-Like Growth Factor I1" @default.
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• W2086448758 doi "https://doi.org/10.1210/jcem.83.6.4872" @default.
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• W2086448758 hasPublicationYear "1998" @default.
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