Neural transplantation in hypogonadal (hpg) mice - physiology and neurobiology

Abstract

The hypogonadal (hpg) mouse mutant has a deletion in the region encoding the hypothalamic gonadotrophic hormone-releasing hormone decapeptide. As a consequence pituitary gonadotrophic hormone synthesis and release is severely curtailed and there is little or no post-natal gonadal development. Grafts of late fetal/early neonatal brain tissue containing the decapeptide-producing neurones into the third ventricle of hpg mice result, in a majority of animals, in a near normalisation of pituitary function with full spermatogenesis in male mice and full follicular and uterine development in females. The vast majority of positive responding females with vaginal opening and uterus growth show no evidence of spontaneous oestrous cycles, ovulation or corpora lutea. These female mice mate with normal males with many of them demonstrating reflex ovulation. In both male and female mutants with successful grafts there is an absence of gonadal steroid negative feedback upon the synthesis and secretion of pituitary gonadotrophic hormones. The releasing factor axon terminals from grafts within the third ventricle identified by immunohistochemical methods are targeted specifically to the median eminence. There is evidence for host innervation of grafts, but how specific this is for the control of gonadotrophic hormone-releasing hormone cell bodies remains to be elucidated.