Implantation of fetal preoptic area into the lateral ventricle of adult hypogonadal mutant mice: the pattern of gonadotropin-releasing hormone axonal outgrowth into the host brain.

Transplantation of fetal preoptic area tissue containing gonadotropin-releasing hormone neurons into the third ventricle of male hypogonadal mice resulted in an elevation of pituitary gonadotropin levels and correction of hypogonadism. This reversal of the neuroendocrine deficit was correlated with innervation of the median eminence by gonadotropin-releasing hormone axons. The specificity of fiber outgrowth suggested that local neuromodulatory factors might guide these axons to the nearby median eminence. To test this hypothesis, 14 adult hypogonadal males received unilateral fetal preoptic area grafts into the lateral ventricle, a site distant from the median eminence. After four months, healthy grafts containing numerous gonadotropin-releasing hormone neurons were seen in 9 hosts. However, none of these grafts corrected the hypogonadism of the host and there was no gonadotropin-releasing hormone innervation of the median eminence in any of these animals, thus demonstrating that the presence of gonadotropin-releasing hormone neurons in the ventricular space is itself not sufficient to stimulate the pituitary-gonadal axis. Instead, gonadotropin-releasing hormone axons coursed in the host fimbria, fornix, corpus callosum, and stria terminalis. These fibers could be traced into the anterior hippocampal area, medial and lateral septum, and the anterior hypothalamus. The distribution of these fibers included a number of regions which receive gonadotropin-releasing hormone fiber input in the normal mouse. These findings show that gonadotropin-releasing hormone neurons transplanted into the lateral ventricle can survive and extend processes into the host brain, often projecting to sites of normal gonadotropin-releasing hormone innervation. Their success in contacting these sites suggests that gonadotropin-releasing hormone fiber outgrowth may be influenced by regionally specified trophic and/or guidance factors.