Hypogonadism in the mutant hpg mouse is characterized by a deficiency of hypothalamic gonadotropin releasing hormone (GnRH). Affected male mice exhibit immature reproductive organs, small abdominal testes and low pituitary and plasma gonadotropin concentrations. Recent studies have demonstrated the potential of fetal brain transplants to establish functional connections with host tissues. We therefore sought to use this approach to correct the hpg deficit. Fetal preoptic area (POA) (a site of GnRH production) from unaffected animals of the hpg strain was transplanted into the anterior third ventricle of adult hpg mice. We report that in such implanted animals, killed 2 months post-implantation, the POA grafts contained GnRH neurones, from which GnRH-positive fibres could be traced to capillaries of the median eminence. Hypothalamic GnRH and pituitary and plasma gonadotropin concentrations were increased compared with levels in untreated (hpg) animals. The testes were enlarged and had descended into the scrotum. Evidence of full spermatogenesis and interstitial cell development was present in testicular sections. No such effects were seen with transplants of cortical tissue.

Gonadotropins-releasing hormone (Gn-RH) in selected regions of the female rat brain was measured by radioimmunoassay. Detectable immunoreactive Gn-RH was found in the anterior hypothalamic-septal region and in the mid-hypothalamic (arcuate-median eminence) region. Gn-RH was several times higher in the middle region than in the anterior region. Gn-RH was undetectable in the posterior hypothalamic region, frontal cerebral cortex and pineal glands, as well as in random blood samples, and low to undetectable in anterior pituitary glands. Gn-RH activity varied during the estrous cycle and after castration. In the mid-hypothalamic region, Gn-RH content was lowest throughout diestrus and in late morning and early afternoon of proestrus, and highest early in the morning of proestrus and during estrus. A significant decrease at mid-day was only found on the day of proestrus, a few hours prior to the critical period for LH release. In the anterior hypothalamic region, low Gn-RH activity was found from 1200 h of estrus to 1200 h of diestrus-2. A comparatively higher activity was seen at 1700 h of diestrus-2 and also from 1400 h of proestrus to 0800 h of estrus. Twenty-one days after ovariectomy, Gn-RH in the mid-hypothalamic region was significantly lower than the lowest values seen during the estrous cycle, while Gn-RH in the anterior hypothalamic region remained between low and high values seen during the cycle, being significantly higher than the low values. The changes observed during the estrous cycle and after castration suggest that gonadal steroids play a direct role in the control of hypothalamic Gn-RH. These data also demonstrate that Gn-RH varies in a different way in the anterior and mid-hypothalamic regions.

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Neural structures containing LHRH were characterized in the hypothalamus of the rhesus monkey by four different antisera to the hormone and an immunoperoxidase technique. Immunoreactive perikarya were present in a continuum from the septal-preoptic region anteriorly to the premammillary nucleus posteriorly. These cells were more concentrated in the pericommissural and tubero-infundibular regions. Reactive axons in the median eminence appeared to originate from the positive perikarya in the medial basal hypothalamus; this projection forms a tubero-infundibular tract containing LHRH. In addition, substantial numbers of fibers which entered the median eminence continued down the infundibular stalk and into the posterior pituitary. Other axons appeared to originate in the pericommisural region and projected to the organum vasculosum of the lamina terminalis. Scattered positive fibers were also present in other hypothalamic areas, especially in the periventricular zone and medical mammillary nucleus.