The long-term objectives are to determine whether hypothalamic control of GRF and SRIF involves self-regulation (ultrashort-loop feedback) of each of these neuropeptides on its own neurosecretion and/or the action of each of these neurohormones to regulate the hypothalamic release of the other, and to establish what the implications of such control systems are for the regulation of pulsatile GH release. Since hypothalamic dysfunction has been implicated in GH deficiency and short stature and could be involved in gigantism and acromegaly, it is pertinent to examine possible mechanisms of autoregulation and reciprocal control of GRF and SRIF since disruption of these could function in disordered GH secretion.
The specific aims proposed to accomplish this are: 1. to determine in which hypothalamic nuclei administered GRF and SRIF are active to alter pulsatile GH secretion and whether these nuclei correspond to areas containing GRF and SRIF neuronal elements; 2. to collect information on the physiological function of GRF and SRIF autoregulation or reciprocal control in pulsatile GH secretion by using a SRIF antagonist and GRF and SRIF antisera for passive immunoneutralization studies; 3. to generate GRF and SRIF antisera in rabbits for the establishment of GRF and SRIF radioimmunoassays, for passive immunoneutralization studies, and for immunohistochemistry; 4. to determine whether administered GRF and SRIF have direct actions on their own release and/or on the release of each other by using the superfusion of hypothalamic slices and median eminences; 5. to determine effects of administered GRF and SRIF on the hypothalamus of the monosodium-glutamate-treated, GRF-deficient rat and the implications for pulsatile Gh release; 6. to observe the anatomical associations of GRF and SRIF neuronal elements at the light microscopic level to underpin the in vivo and in vitro findings of specific aims 1-5 above.
