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Developmental changes and differential regulation by testosterone and estradiol of growth hormone receptor expression in the rabbit

Yu YM, Domené HM, Sztein J, Counts DR, Cassorla F. Developmental changes and differential regulation by testosterone and estradiol of growth hormone receptor expression in the rabbit. Eur J Endocrinol 1996;135:583–90. ISSN 0804–4643

To investigate the effects of testosterone and estradiol (E₂) on growth hormone receptor (GH-R) gene expression, we measured GH-R mRNA levels in relation to the changes of sex steroid concentrations in the normal male rabbits aged 1–12 months and after administration of testosterone or E₂ to castrated male rabbits. In the normal animals, E₂ levels were below the detection limit in all age groups, and testosterone levels were below the detection limit at 1 month, increased at 2 months and reached the plateau of the adult levels after 4 months. Liver GH-R mRNA levels were low at 1 month, reached a peak at 2 months and then decreased slightly thereafter. In the castrated animals, liver and growth plate GH-R mRNA levels were increased in the testosterone-treated group (162.0 ± 12.0%, p < 0.025; 128.4 ± 7.6%; p < 0.025) and reduced in the E₂-treated group (29.6 ± 6.2%, p < 0.005; 53.6 ± 11.3%, p < 0.025). Sex steroid administration did not result in any significant change in GH-R mRNA levels in striated muscle, kidney and heart. Serum GH concentrations were increased in E₂ (15.3 ± 7.7 µg/l vs 4.8 ± 2.2 µg/l, p < 0.025) but the increase was not significant in testosterone-treated animals (8.4 ± 7.7 µg/l vs 4.8 ± 2.2 µg/l). Both testosterone and E₂ treatment resulted in a reduction of mean serum growth hormone-binding protein (GHBP) levels compared to control animals (1077 ± 422 pmol/l, p < 0.01; 1137 ± 443 pmol/l, p < 0.01; 2308 ± 565 pmol/l). We conclude that in addition to their stimulatory effect on GH secretion, testosterone and E₂ have opposite effects on GH-R gene expression in liver and growth plate in the rabbit. The modulation of GH-R expression by sex steroids may be important for growth during sexual maturation in mammals.

Yu M Yu, MD, 11600 Bootjack Court, Gaithersburg, MD 20878, USA

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