The overall objective is to understand the mechanisms whereby growth- related cues influence the rate of sexual maturation and onset of puberty. Specifically, to determine the neurotransmitter pathways which transduce the signal from growth-related cues to the reproductive system. The specific aims of the proposed research are l) to determine if delayed puberty, caused by growth restriction, is due to central nervous system inhibition of the GnRH neurosecretory system, 2) to determine the neurotransmitter pathways which may be involved in the inhibition and/or lack of stimulation of the GnRH neurosecretory system during delayed puberty caused by growth restriction, and 3) to determine the neurotransmitter pathways which are activated and/or released from inhibition resulting in a rise in GnRH (and therefore LH) secretion and onset of estrous cycles during realimentation following delayed puberty due to growth restriction. Several experimental approaches and methodologies will be used to attain these objectives. The prepubertal female rat will be used as the animal model, in which puberty is delayed by dietary-induced growth restriction to 75-80 g body weight. In this model, LH pulse frequency is low, but can be reinstated to the normal post-pubertal high level by ad libitum feeding. In addition, following realimentation, estrous cycles resume within one week. To determine if delayed puberty in this model is due to central nervous system inhibition, two approaches will be utilized. Experiment l will investigate the effects of the non-specific central nervous system inhibitor, sodium pentobarbital, on LH secretion in growth- restricted rats. Experiment 2 will determine the effects of specifically located hypothalamic knife-cuts on LH secretion and estrous cycles in the growth-restricted rat. To determine the neurotransmitter pathways which may be involved in the inhibition and/or lack of stimulation of the GnRH neurosecretory system during delayed puberty caused by growth restriction, several experiments are proposed. A series of studies will investigate the effects of cerebroventricular administration of a variety of neurotransmitter agonists and antagonists on reproductive function. Neurotransmitter pathways which will be investigated include opioid, dopamine, norepinephrine, serotonin, gamma-amino butyric acid, NPY, and glutamate. These pathways will be investigated in individual as well as in combined studies. To determine the neurotransmitter pathways which are activated and/or released from inhibition resulting in a rise in GnRH (and therefore LH) secretion and onset of estrous cycles during realimentation following delayed puberty due to growth restriction, similar approaches to those used in Specific Aim 2 will be employed. Neurotransmitter pathways which will be investigated include opioid, dopamine, norepinephrine, serotonin, gamma-amino butyric acid, NPY, and glutamate. This combined approach will determine the neural interactions which transduce the signal between growth and metabolism and reproductive activity. The results of this project have relevance to the understanding of puberty, and to other physiological conditions in which the reproductive system is less active due to metabolic perturbations, such as during extensive exercise, postpartum anovulation, or during metaboliC disease states, for example, anorexia nervosa.