description): Acquisition of a critical body mass is thought to be important for the initiation of puberty. Although a number of studies in a variety of species have linked body size to puberty, the signal responsible for increasing pulsatile gonadotropin hormone releasing hormone (GnRH) secretion and initiating puberty is unknown. However, the recent identification of the protein leptin has lead to the hypothesis that a developmental increase in leptin, derived from accumulating fat mass, acts centrally to increase GnRI-1 secretion and a parallel increase in the pituitary release of the gonadotropins, resulting in gonadal activation. While the hypothesis that leptin initiates puberty has yet to be adequately tested in primates which, unlike rodents, show a protracted period of post-natal development prior to puberty. Before prospective studies can be initiated in primates, additional preliminary data derived from a female monkey model are needed to A) define precisely the temporal relationship between prepubertal increases in diurnal leptin concentrations and the emergence of nocturnal gonadotropin release and B) develop a protocol to assess how the sustained administration of leptin affects GnRH secretion in well nourished females.
Specific Aim 1 will test the hypothesis that the developmental rise in nocturnal leptin secretion precedes the emergence nocturnal gonadotropin secretion in females.
Specific Aim 2 will test the hypothesis that the timing of daytime food intake influences the pattern but not amplitude of the diurnal leptin secretion.
Specific Aim 3 will determine the dose of sustained administration leptin that reverses the fasting-induced suppression of gonadotropin secretion and will test the hypothesis that leptin binding protein facilitates leptin's access to the brain and effects on neuroendocrine systems.
Specific Aim 4 will obtain information on the efficacy of leptin administration to immature females on metabolic and reproductive parameters.
| Wilson, Mark E; Kinkead, Becky (2008) Gene-environment interactions, not neonatal growth hormone deficiency, time puberty in female rhesus monkeys. Biol Reprod 78:736-43 |
| Wilson, Mark E; Fisher, Jeffrey; Chikazawa, Kathy et al. (2003) Leptin administration increases nocturnal concentrations of luteinizing hormone and growth hormone in juvenile female rhesus monkeys. J Clin Endocrinol Metab 88:4874-83 |
