The broad objective of this proposal is to investigate the hypothalamic mechanisms which mediate the ultrashort-loop feedback (autoinhibition) and reciprocal regulation of growth hormone- releasing factor (GRF) and somatostatin (somatotropin release- inhibiting factor, SRIF), and to observe how such systems of hypothalamic regulation influence pulsatile growth hormone (GH) secretion. The reason for investigating hypothalamic GRF and SRIF selfregulating systems is because disruption of these mechanisms may contribute to the pathogenesis of dwarfism, gigantism, acromegaly, and pituitary tumor formation in humans.
The specific aims proposed to investigate the mechanisms of GRF and SRIF ultrashort-loop feedback are: 1. to characterize further the mode by which intrahypothalamic SRIF produces its ultrashort-loop feedback effect in vivo through the use of GRF and SRIF peptide antagonists; 2. to examine the possible physiological participation of GABA neurons (interneurons?) in mediating GRF and SRIF ultrashort-loop feedback in vivo; 3. to obtain in vitro correlates concerning the role of GABA in mediating GRF and SRIF ultrashort-loop feedback; 4. to detect and measure GRF receptor activity which may mediate GRF ultrashort-loop feedback in the hypothalamus; 5. to determine whether hypothalamic GRF receptor characteristics are altered by various pharmacological or physiological states as they relate to modulation of GRF autofeedback.
