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, chronic circulating levels of endogenous growth hormone (GH) were studied in transgenic mice with ectopic overexpression of the human growth hormone-releasing hormone (h-GH-RH) gene. In comparison with their normal littermates, transgenic h-GH-RH mice had elevated plasma levels of GH, prolactin (PRL), and corticosterone. In addition, they had elevated body, liver, kidney, spleen, and pituitary weights compared with normal mice. Testis and seminal vesicle weights were also increased in transgenic mice. Although basal plasma luteinizing hormone (LH) levels, plasma estradiol levels in females, and plasma testosterone levels in males did not differ significantly between normal and transgenic animals, the LH response to castration was severely impaired in transgenic mice of both sexes. Among the biogenic amines studied in the hypothalamus, only dopamine concentrations were significantly lower in transgenic animals compared with their normal littermates. This decrease in hypothalamic dopamine may be related to the hyperprolactinemia in transgenic animals. In vitro, pituitaries from transgenic mice released significantly higher amounts of GH, and although the basal release of LH was not different in both normal and transgenic mice, the response to gonadotropin-releasing hormone was significantly smaller in transgenic mice. Cultured anterior pituitary cells from transgenic mice secreted high quantities of GH and PRL in vitro, but these quantities significantly decreased from 1 to 8 wk in culture. These results show that high, persistent levels of circulating endogenous GH induce alterations in neuroendocrine functions related to the hypothalamo-pituitary-gonadal and the hypothalamo-pituitary-adrenal axes.