Neural grafts and the restoration of pituitary and gonadal function in hypogonadal (HPG) mice

The hypogonadal mouse is a mutant deficient in the hypothalamic gonadotrophic hormone releasing hormone (GnRH) with a consequent extreme depletion in pituitary luteinising hormone (LH) and follicle stimulating hormone (FSH) and a failure of post-natal gonadal growth. Grafting late foetal-early neonatal preoptic area (POA) tissue into the third ventricle of adult hpg mice resulted in increased GnRH receptors in the pituitary, increased synthesis and secretion of LH and FSH, and full stimulation of spermatogenesis in the male and folliculogenesis in the females. Although the POA grafts in the female stimulated ovarian and uterine growth and vaginal opening, so far there has been no evidence of ovarian cyclicity and the females did not ovulate spontaneously. However the increased ovarian steroidogenesis stimulated full female mating behaviour and a high percentage of the females became pregnant. The evidence suggests that these females must have ovulated reflexly upon mating, raising the question as to where in the graft the mating response was transduced. Over 90% of GnRH positive axons ended up innervating the median eminence, suggesting that even in adult mice this region of the brain retains its trophic capacity. In male hpg mice treated with testosterone there was no evidence of a negative feedback upon the graft induced elevation of pituitary LH and FSH content, suggesting that a site of androgen negative feedback may be at a CNS site removed from the GnRH neurone.