Morphological changes to somatotroph cells and in vitro individual GH release, in male rats treated with recombinant human GH

The effect of in vivo chronic administration of recombinant human growth ho rmone (rhGH) on morphology and individual GH release in somatotroph cells w as evaluated in young male Wistar rats. Over an 18-day period, 30-day-old m ale rats were injected daily with 1.5 1U rhGH/kg (GPG group) or saline (VPG group) by subcutaneous injection. Electron-immunocytochemical, ultrastruct ural and morphometric studies of somatotroph cells were carried out. Additi onally, rat pituitary cells were dispersed and overall and individual GH re lease was studied by radioimmunoassay and cell immunoblot assay (quantified by image analysis), respectively. The ultrastructure and size of somatotro ph cells did not change, but volume density of secretion granules was reduc ed (p<0.01) by previous in vivo GH treatment. At four days, basal GH releas e of rat pituitary cell monolayer cultures was lower in the GPG group than in the VPG group (p<0.05); after 12 hours of culture, GHRH stimulation of G H release was lower in the GPG group than in the VPG group (p<0.05), and GH RH+SRIH inhibited GH release in the GPG group (p<0.05), but not in the VPG group. The percentage of somatotroph cells was not modified, but the ratio of strongly/weakly GH-immunostained cells had changed; weakly GH-immunostai ned cells increased from 34% to 55%. Moreover, in vitro treatment with GHRH , SRIH, and both, easily changed the strongly/weakly GH-immunostained cell ratio. Individual GH re:lease, however, was not changed by previous in vivo GH treatment, although GHRH preferably stimulated a subpopulation of GH ce lls and SRIH did not :inhibit individual GH release. These data suggest tha t exogenous chronic rhGH treatment down-regulates somatotroph function by m odifying the proportion of GH cell subpopulation.