NEUROENDOCRINOLOGY OF PUBERTY AND SEXUAL DEVELOPMENT

The proposal is aimed at gaining new insight into the developmental
processes that underlie the maturation of the reproductive hypothalamus
and, hence, the onset of female puberty. Utilizing the rat as the animal
model, experiments are proposed to examine the hypothesis that brain
neuronotrophic factors regulate the development of the hypothalamic LHRH-
secreting system, which culminates when a discharge of LHRH release
triggers the first preovulatory surge of gonadotropins. To this end, the
following specific aims are proposed. 1. To document the hypothesis that nerve growth factor (NGF) and
transforming growth factor alpha (TGFalpha), as well as their respective
receptors, are expressed in the hypothalamus, and to examine their
contribution to the developmental regulation of LHRH secretion. 2. To examine the hypothesis that TGFalpha facilitates the morphological
and functional differentiation of LHRH neurons and to determine whether NGF
is trophic for LHRH neurons and/or a neuronal system regulatory to LHRH
function. 3. To examine the hypothesis that hypothalamic trophic factors, and in
particular the epidermal growth factor receptor EGFr/TGFalpha ligand system
can influence LHRH synthesis by directly regulating transcriptional
activity of the LHRH gene. 4. To examine the hypothesis that TGFalpha is one of the neuronotrophic
factors that contribute to the peripubertal, gonadal-independent activation
of LHRH release. The accomplishment of these aims depends on the team participation of one
neuroendocrinologist, one molecular biologist, and two morphologists, and
on the integrated use of neuroendocrine, neurobiology and molecular biology
approaches.