Debeljuk L, Steger R W, Wright J C, Mattison J, Bartke A
Department of Physiology, Southern Illinois University School of Medicine, Carbondale 62901, USA.
Endocrine. 1999 Oct;11(2):171-9. doi: 10.1385/ENDO:11:2:171.
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.
在本研究中，我们在异位过表达人生长激素释放激素（h-GH-RH）基因的转基因小鼠中，研究了内源性生长激素（GH）长期高循环水平诱导的神经内分泌改变。与正常同窝小鼠相比，转基因h-GH-RH小鼠的血浆GH、催乳素（PRL）和皮质酮水平升高。此外，与正常小鼠相比，它们的体重、肝脏、肾脏、脾脏和垂体重量增加。转基因小鼠的睾丸和精囊重量也增加。虽然正常和转基因动物之间基础血浆促黄体生成素（LH）水平、雌性血浆雌二醇水平和雄性血浆睾酮水平没有显著差异，但两性转基因小鼠对去势的LH反应严重受损。在所研究的下丘脑生物胺中，与正常同窝小鼠相比，转基因动物中只有多巴胺浓度显著降低。下丘脑多巴胺的这种降低可能与转基因动物的高催乳素血症有关。在体外，转基因小鼠的垂体释放的GH量显著更高，虽然正常和转基因小鼠的LH基础释放没有差异，但转基因小鼠对促性腺激素释放激素的反应显著更小。转基因小鼠培养的垂体前叶细胞在体外分泌大量的GH和PRL，但在培养1至8周后，这些量显著减少。这些结果表明，内源性GH的持续高水平循环会诱导与下丘脑-垂体-性腺轴和下丘脑-垂体-肾上腺轴相关的神经内分泌功能改变。
