TESTOSTERONE FEEDBACK ON GONADOTROPIN-SECRETION AND GENE-EXPRESSION IN TRANSGENIC MICE EXPRESSING HUMAN GROWTH-HORMONE GENE

To determine the effects of testosterone on the regulation of gonadotr opins in metallothionein-1/human growth hormone (MT/hGH) transgenic mi ce, basal and gonadotropin-releasing hormone (GnRH)-stimulated luteini zing hormone (LH) and follicte-stimulating hormone (FSH) release from incubated pituitaries, as well as pituitary content of LH, FSH, and mR NA for their respective beta subunits, were measured in normal and tra nsgenic males that were injected with testosterone propionate (5 mu g/ g body weight; 24 hours before autopsy), injected with oil vehicle, ca strated for 10 days, or sham operated. In normal (non-transgenic) male s, exogenous testosterone induced the expected suppression, and castra tion induced the expected stimulation of various parameters of gonadot ropin synthesis and release. In contrast, in testosterone-treated and in castrated MT/hGH transgenic mice the release of LH and the pituitar y levels of LH-beta mRNA did not differ from the corresponding values measured in vehicle-injected and sham-operated transgenic controls. Pi tuitary LH content was elevated in testosterone-treated MT/hGH transge nic mice but was not changed in castrated transgenic males. The change s in pituitary levels of FSH and FSH-beta mRNA and in FSH release in M T/hGH transgenic mice in response to testosterone and castration were different from the changes in LH and LH-beta mRNA in the same mice, bu t similar to the changes of FSH and FSH-beta message produced in norma l mice by identical treatments. We suggest that hGH expression attenua tes the effects of testosterone on the mechanisms controlling LH relea se, with less influence on testosterone regulation of LH synthesis. Th ese effects of hGH expression appear to be selective for LH, without i nfluencing the FSH control system.