Pituitary and gonadal function in hypogonadotrophic hypogonadal (hpg) mice bearing hypothalamic implants

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Abstract
GnRH [gonadotropin releasing hormone] receptor values are 30-50% of normal in pituitaries of hpg male mice, and testicular LH [luteinizing hormone] receptors only 8% of normal (160.4 .+-. 17.6 and 2013 .+-. 208.1 fmol/testis respectively). In male hpg mice bearing fetal preoptic area (POA) hypothalamic implants for 10 days there was no change in pituitary GnRH receptors, pituitary gonadotropin content or seminal vesicle weight. Testicular weights and LH receptors were doubled in 4/10 mice and 2 had increased serum FSH levels. Between 26 and 40 days after implantation pituitary GnRH receptors and pituitary LH increased to normal male levels, although at 40 days serum and pituitary FSH concentrations had reached only 50% of normal values. Testicular and seminal vesicle weights increased > 10-fold by 40 days after implantation and LH receptors of 70% of normal. In hpg female mice bearing hypothalamic implants for 30-256 days pituitary gonadotropin concentrations were normal, even though GnRH receptors reached only 60% of normal values (6.18 .+-. 0.4 and 9.8 .+-. 0.4 fmol/pituitary respectively). Serum FSH was substantially increased from values of < 30 ng/ml in hpg mice to within the normal female range in hypothalamic implant recipients. Ovarian and uterine weights increased after hypothalamic grafting from only 4-5% to > 74% of normal values. LH receptors increased from 6.5 .+-. 1.3 fmol ovary for hpg mice to 566.9 .+-. 39.2 fmol/ovary for implant recipients. Vaginal opening occurred .apprx. 23 days after implantation and these animals displayed prolonged periods of estrus. Brain sections from animals with POA implants revealed that a prerequisite for restoration of near-normal pituitary and gonadal function was the anatomical connection of donor tissue to the median eminence of the recipient. Implantation of fetal hypothalamic tissue largely reverses the GnRH deficiency of male and female hpg mice. The pituitary-gonadal response to hypothalamic implantation follows a time-course similar to that during normal sexual maturation, but is more variable than the previously reported effects of multiple GnRH injections. Although hypothalamic grafts in female hpg mice result in almost normal pituitary and ovarian endocrine function, cyclic ovarian activity does not occur, possibly reflecting the lack of appropriate neural control over the implanted tissue.