INTERACTIONS OF HUMAN GROWTH-HORMONE AND PROLACTIN ON PITUITARY AND LEYDIG-CELL FUNCTION IN ADULT TRANSGENIC MICE EXPRESSING THE HUMAN GROWTH-HORMONE GENE

Adult male transgenic mice expressing the human growth hormone (hGH) gene are hypoprolactinemic. To evaluate the effects of exogenous prolactin (PRL) and endogenously secreted hGH on pituitary and Leydig cell function, adult male transgenic and nontransgenic mice (10-16 wk of age) were treated s.c. with either saline-polyvinylpyrrolidone (PVP) or oPRL (100 mu-g/mouse) in saline-PVP. Animals were treated twice daily; a total of 7 injections were given. One hour after the last injection, each group of mice was treated i.p. either with saline or oLH (0.3 mu-g/g BW); 2 h later, blood was obtained via heart puncture. Plasma FSH, LH, PRL, androstenedione (A-dione), and testosterone (T) levels were measured by validated RIAs. Basal PRL levels were significantly lower (p < 0.001) and basal LH concentrations were significantly higher (p < 0.01) in transgenic than in nontransgenic mice. Administration of PRL significantly decreased (p < 0.01) plasma LH levels in transgenic mice, whereas similar treatment of nontransgenic mice increased (p < 0.01) circulating LH concentrations. Plasma FSH levels were unaffected in transgenic and nontransgenic mice treated with saline or PRL. Basal plasma A-dione and T levels were similar in both groups of animals and were significantly increased after treatment with LH. Administration of PRL increased T levels in transgenic and nontransgenic mice, but the T response to LH treatment was greater in PRL-treated transgenic mice, indicating the synergistic effect of hGH in the biosynthesis of T. Since hyperprolactinemia was previously shown to increase LH secretion in normal adult male mice, our results demonstrate that, despite hyposecretion of PLR by the in situ pituitary gland of transgenic mice, plasma LH levels are elevated-probably as a result of the PRL-like activity of hGH. However, acute PRL treatment of transgenic mice decreased plasma LH levels and was associated with increases in circulating T levels. This suggests that exogenous PRL in conjunction with endogenous hGH may have increased the hypothalamic-pituitary sensitivity to the negative feedback effect of T. These results also demonstrate that, in addition to altering PRL and LH secretion, endogenously produced hGH modulates the effects of PRL, as well as LH on testicular endocrine function of adult transgenic mice expressing the hGH gene.