Continuous Gonadotropin-Releasing Hormone Infusion Stimulates Dramatic Gonadal Development in Hypogonadal Female Mice'

ABSTRACT Adult hypogonadal (hpg) mice, lacking GnRH, have infantile reproductive systems and levels of pituitary gonadotropins that are lower than normal. The mutant mice respond to brain grafts containing GnRH neurons with gonadal development and increased production of gonadotropins. In view of the substantial literature regarding the nature and necessity of pulsatile GnRH stimulation of gonadotropins, we were not surprised in earlier studies to find that the majority of hpg mice with successful grafts have pulsatile LH secretion. It is not known, however, why LH pulsatility was undetectable in some animals with significant gonadal development. The present experiment was intended to determine the degree to which hpg mice respond to continuous infusion of GnRH via osmotic minipumps. Unexpectedly, female hpg mice exhibited dramatic ovarian and uterine growth after 15 or 30 days of continuous exposure to GnRH, with five-and eightfold increases in ovarian and uterine weights, respectively. Despite evidence of increased gonadotropin secretion in the treated hpg mice, pituitary stores of FSH and LH remained low. Similar treatment of normal female mice for 15 days also depleted pituitary concentrations of LH and FSH without significantly altering gonadal weights or plasma gonadotropin levels. It is clear from the present findings that inferences of pulsatile GnRH secretion based on stimulation of gonadal development in hpg mice should be made with caution