Repair of reproductive deficits by neural transplantation.
Transplantation of brain tissue has been used to ameliorate the genetic lesion of the hypogonadal mutant mouse. This animal does not synthesize gonadotropin-releasing hormone (GnRH) and so has an infantile reproductive system. Implantation of normal fetal or neonatal preoptic area containing GnRH neurons reverses many aspects of the reproductive deficiency. Pituitary and plasma levels of gonadotropins rise, followed by growth of the gonads and sexual organs. Pituitary release of gonadotropins is episodic, suggesting that the grafted tissue is integrated into the "pulse generator." The vast majority of grafted animals do not show castration-induced elevations of luteinizing hormone (LH) nor respond to exogenous steroids with a depression in circulating LH. Negative feedback of gonadal steroids seems to be inoperative. In contrast, some females can show ovulatory surges of LH in response to mating (reflex ovulation), after administration of exogenous steroid (progesterone), and, on rare occasion, ovulation cycles occur spontaneously. Anatomical studies demonstrate that reproductive recovery is dependent on the outgrowth of GnRH axons to the host median eminence. Some but not all of the GnRH neurons within the grafts contribute to this innervation. GnRH axons exit into the host along well-defined pathways, recapitulating in part the paths taken by normal axons. How the graft and host are integrated to produce the panoply of reproductive responses is the subject of current study.
Silverman
A J
AJ
Department of Anatomy and Cell Biology, Columbia University, New York, New York 10032.
Silverman
R C
RC
Gibson
M J
MJ
D000818:Animals; D005260:Female; D007006:Hypogonadism / Q000503:physiopathology*; D008297:Male; D051379:Mice; D009474:Neurons / Q000637:transplantation*; D010906:Pituitary Hormone-Releasing Hormones / Q000172:deficiency / Q000502:physiology*
D010906:Pituitary Hormone-Releasing Hormones