Effects of overexpression of growth hormone-releasing hormone on the hypothalamo-pituitary-gonadal function in the mouse

In this investigation, the neuroendocrine alterations induced by high, chro nic circulating levels of endogenous growth hormone (GH) were studied in tr ansgenic mice with ectopic overexpression of the human growth hormone-relea sing hormone(h-GH-RH) gene. In comparison with their normal littermates, tr ansgenic h-GH-RH mice had elevated plasma levels of GH, prolactin (PRL), an d corticosterone. In addition, they had elevated body, liver, kidney, splee n, and pituitary weights compared with normal mice. Testis and seminal vesi cle weights were also increased in transgenic mice. Although basal plasma l uteinizing hormone (LH) levels, plasma estradiol levels in females, and pla sma testosterone levels in males did not differ significantly between norma l and transgenic animals, the LH response to castration was severely impair ed in transgenic mice of both sexes. Among the biogenic amines studied in t he hypothalamus, only dopamine concentrations were significantly lower in t ransgenic animals compared with their normal littermates. This decrease in hypothalamic dopamine may be related to the hyperprolactinemia in transgeni c animals. In vitro, pituitaries from transgenic mice released significantl y higher amounts of GH, and although the basal release of LH was not differ ent in both normal and transgenic mice, the response to gonadotropin-releas ing hormone was significantly smaller in transgenic mice. Cultured anterior pituitary cells from transgenic mice secreted high quantities of GH and PR L in vitro, but these quantities significantly decreased from 1 to 8 wk in culture. These results show that high, persistent levels of circulating end ogenous GH induce alterations in neuroendocrine functions related to the hy pothalamo-pituitary-gonadal and the hypothalamo-pituitary-adrenal axes.