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

To investigate the effects of testosterone and estradiol (E 2 ) 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 E 2 to castrated male rabbits. In the normal animals, E 2 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 E 2 -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 E 2 (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 E 2 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 E 2 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.