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ORIGINAL RESEARCH ARTICLE

Influence of Estrogen Administration on the Growth Response to Growth Hormone (GH) in GH-Deficient Mice

Department of Medicine, Division of Endocrinology, and the Ilyssa Center for Molecular and Cellular Endocrinology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287

To whom requests for reprints should be addressed at ¹ 1830 East Monument Street #333, Baltimore, MD 21287. E-mail: salvator{at}jhmi.edu

In women who are growth hormone (GH) deficient, exogenous estrogens increase the dosage of GH that is needed to normalize circulating levels of insulin-like growth factor (IGF-1). Serum IGF-1 derives mostly from the liver, and it is unknown whether the peripheral effects of GH are also impaired by estrogens. Because the ultimate effect of GH is longitudinal growth, we have investigated the influence of estrogen administration on the growth response to recombinant mouse GH therapy in prepubertal GH-deficient (GHD) GHRH knockout (GHRHKO) female mice. Twenty-four GHRHKO female mice (4 animals/group) were treated for 4 weeks (from the second to sixth week of age) with the following schedules: Group I, GH only (25 µg/day); Group II, subcutaneous (sc) ethynil estradiol (EE) (0.035 µg/day); Group III, GH + scEE; Group IV, oral (po) EE (0.035 µg/day); Group V, GH + poEE; Group VI, placebo. At the end of the treatment period, we measured uterine weight, total body weight (TBW), body length (nose-anus, N-A), and femur length. In addition, serum IGF-1 levels were measured. Uteri of mice treated with oral or scEE showed similar increases in weight. There was no difference in the increase in longitudinal growth parameters between mice treated with GH alone or with GH in association with oral or scEE. Serum IGF-1 decreased in animals treated with GH + scEE, compared with GH group, but no group was significantly different from placebo. These results show that subcutaneous or oral EE does not reduce the growth response to GH in female GHD mice.

Key Words: ethynil estradiol • GHRH gene ablation • growth

This article has been cited by other articles:

				M. Alba, D. Fintini, A. Sagazio, B. Lawrence, J.-P. Castaigne, L. A. Frohman, and R. Salvatori Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse Am J Physiol Endocrinol Metab, December 1, 2006; 291(6): E1290 - E1294. [Abstract] [Full Text] [PDF]