NEUROBIOLOGICAL MECHANISMS TIMING PRIMATE PUBERTY

Description of projects available to graduate students:
Puberty in man and other higher primates is triggered by a resurgence in hypothalamic pulsatile GnRH release that has been held in check since infancy by a neurobiological “brake” imposed on the GnRH neuronal network. The notion of a brake is strictly conceptual and may result from withdrawal of an excitatory transynaptic or glial input, loss of an inhibitory input, or the combination of the two. Dr. Plant’s laboratory is examining these possibilities using the rhesus monkey as an experimental surrogate for the human situation. Current work focuses on the hypothesis that down regulation of KiSS1 (the gene encoding for kisspeptin) during juvenile development when GnRH pulsatility is arrested is a major component of the brake. KiSS1 expressing neurons in the primate hypothalamus are found in the arcuate nucleus and regulate GnRH pulsatility at axo-axonal contacts on GnRH neuronal terminals in the median eminence. GnRH neurons express the kisspeptin receptor (KiSSR1); a G protein couple receptor initially named, GPR54. The extent to which this receptor is found in the median eminence is under study. Another question being addressed is what is the nature of the physiological control system (i.e. a pubertal clock or a growth tracking device in the primate brain) that governs the developmental expression of KiSS1 in the arcuate nucleus. An answer to this question will probably solve the mystery of human puberty.

Techniques graduate student will learn:
In situ hybridization, fluorescence immunohistochemistry and confocal analysis, qRT-PCR, microarrays, receptor binding with radioactive and fluorescent probes.