GROWTH HORMONE IN PITUITARY AND TESTICULAR FUNCTION

生殖产生不利的影响，在人类肢端肥大症由于过量的生长激素分泌。此外，在男性中，先天性GH抵抗是由于突变的GH受体（Laron综合征）与性成熟延迟有关，这表明GH在生殖中的作用。然而，目前尚不清楚这些变化是否通过脑垂体介导。为了解决这一问题，将在GH受体敲除小鼠（GHR-KO小鼠; Laron综合征模型）和表达人GHRH基因的转基因小鼠（GHRH小鼠;肢端肥大症模型）中评价垂体和睾丸功能。在GHR-KO雄性小鼠中，LH对GnRH治疗的反应是睾酮浓度增加，而LH对GnRH治疗的反应降低。具体的目的是评估为什么垂体和睾丸功能在这两个系列的小鼠改变。为了评价垂体和睾丸功能的改变是否是由于缺乏IGF-I分泌，将用IGF-I处理GHR-KO小鼠，或者为了确定该作用是否是由于高泌乳素血症，将通过多巴胺激动剂处理抑制泌乳素分泌。为了检查GHRH小鼠中增加的循环睾酮水平是否是由于IGF-I分泌增加所致，将用生长抑素处理这些动物以抑制IGF-I分泌。在这些实验中，将通过测量促性腺激素对GnRH治疗的反应来评价垂体功能，并评估垂体中LH β和FSH β mRNA的表达。将通过评价睾酮和睾酮前体对LH治疗的反应来确定睾丸功能。长期目标是研究外源性GH对实验动物生殖的长期影响。这些研究可能会对GH在衰老中的使用产生一些影响。

Re production is adversely affected in human acromegaly due to excess GH secretion. Also in men, congenital GH resistance is due to mutated GH receptors (Laron syndrome) is associated with delay in sexual maturation, suggesting a role of GH in reproduction. However, it is not know whether these changes are mediated via the pituitary gland. To address this issue, pituitary and testicular functions will be evaluated in GH receptor knockout (GHR-KO mice; a model for Laron syndrom) and transgenic mice expressing the human GHRH gene (GHRH mice; a model for acromegaly). In GHR-KO male mice, the LH response to GnRH treatment is testosterone concentrations are increased, whereas the LH response to GnRH treatment is decreased. The specific aims are to assess why the pituitary and testicular functions are altered in these two lines of mice. To evaluate whether the alterations in pituitary and testicular function are due to lack of IGF-I secretion, GHR-KO mice will be treated with IGF-I or to determine whether the effects are due to hyper prolactinemia, prolactin secretion will be suppressed by treatment with a dopamine agonist. To examine whether the increased circulating testosterone levels in GHRH mice is due to increased IGF-I secretion, these animals will be treated with somatostatin to suppress IGF-I secretion. In these experiments, the pituitary function will be evaluated by measuring the gonadotropin response to GnRH treatment and assess LHbeta and FSHbeta mRNA expressions in the pituitary gland. The testicular function will be determined by evaluating the testosterone and the testosterone precursor responses to LH treatment. The long-term goals are to examine the long-term effects of exogenous GH on reproduction in experimental animals. These studies may have some impact on the usage of GH in aging.