GONADOTROPIN-SECRETION, SYNTHESIS, AND GENE-EXPRESSION IN 2 TYPES OF BOVINE GROWTH-HORMONE TRANSGENIC MICE

Expression of the mouse metallothionein-I (MT) promoter/bovine growth hormone (bGH) or the phosphoenolpyruvate carboxykinase (Pepck) promote r/bGH fusion genes in male transgenic mice is associated with alternat ions in adenohypophyseal function and fertility. To determine the effe cts of these gene constructs on gonadotropin synthesis and secretion, we have examined basal and GnRH-stimulated LH and FSH release in vitro using static incubations and perifusions of the pituitary; we have al so examined pituitary content of LH, FSH, LHbeta mRNA, and FSHbeta mRN A in MT/bGH and Pepck/bGH transgenic mice as well as in normal mice. I n addition, we have measured LH and FSH release from normal pituitarie s transplanted under the kidney capsules of Pepck/bGH transgenic or no rmal mice. We found that in Pepck/bGH transgenic mice, pituitary conte nts of FSH and FSHbeta mRNA were reduced, while FSH release in vitro i n pituitary incubations and perifusions was increased. Steady-state le vels of LHbeta mRNA as well as LH responses to GnRH in perifusions wer e reduced; LH release in incubations and pituitary LH content were not changed; and basal LH secretion in perifusions was increased. In MT/b GH transgenic mice, in which peripheral bGH levels are much lower than in Pepck/bGH mice, similar trends were observed, but most of the appa rent differences between transgenic and normal animals were not statis tically significant. When normal pituitaries were transplanted under t he kidney capsules of Pepck/bGH transgenic mice, the expected decrease in LH and FSH secretion was attenuated and the response to GnRH stimu lation was lost. We suggest that in transgenic mice expressing the bGH gene, there is a pretranslational inhibitory influence on FSHbeta and LHbeta gene expression, combined with stimulatory influences on gonad otropin release at both the hypothalamic and the pituitary levels. Pla sma gonadotropin levels appear to reflect the balance of these inhibit ory and stimulatory influences. The actions of these putative influenc es on the synthesis and release of LH and FSH may be different, leadin g to divergent changes of pituitary content and release of LH and FSH in these animals.