Gonadotropin secretion, synthesis, and gene expression in two types of bovine growth hormone transgenic mice

Abstract

Expression of the mouse metallothionein-I (MT) promoter/bovine growth hormone (bGH) or the phosphoenolpyruvate carboxykinase (Pepck) promoter/bGH fusion genes in male transgenic mice is associated with alternations in adenohypophyseal function and fertility. To determine the effects 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 also examined pituitary content of LH, FSH, LHβ mRNA, and FSHβ mRNA in MT/bGH and Pepck/bGH transgenic mice as well as in normal mice. In addition, we have measured LH and FSH release from normal pituitaries transplanted under the kidney capsules of Pepck/bGH transgenic or normal mice. We found that in Pepck/bGH transgenic mice, pituitary contents of FSH and FSHβ mRNA were reduced, while FSH release in vitro in pituitary incubations and perifusions was increased. Steady-state levels of LHβ mRNA as well as LH responses to GnRH in perifusions were reduced; LH release in incubations and pituitary LH content were not changed; and basal LH secretion in perifusions was increased. In MT/bGH transgenic mice, in which peripheral bGH levels are much lower than in Pepck/bGH mice, similar trends were observed, but most of the apparent differences between transgenic and normal animals were not statistically significant. When normal pituitaries were transplanted under the kidney capsules of Pepck/bGH transgenic mice, the expected decrease in LH and FSH secretion was attenuated and the response to GnRH stimulation was lost. We suggest that in transgenic mice expressing the bGH gene, there is a pretranslational inhibitory influence on FSHβ and LHβ gene expression, combined with stimulatory influences on gonadotropin release at both the hypothalamic and the pituitary levels. Plasma gonadotropin levels appear to reflect the balance of these inhibitory and stimulatory influences. The actions of these putative influences on the synthesis and release of LH and FSH may be different, leading to divergent changes of pituitary content and release of LH and FSH in these animals.