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.
