The proposed research is intended to apply the recent biochemical and pharmacological advances in GABA function to physiology in order to obtain a more accurate determination of GABA's significance in regulation of anterior pituitary secretion. The existing controversy over the physiological significance of GABA to hormone release results from the low potency of GABA in vivo and in vitro. It is now becoming apparent that benzodiazepines and endogenous inhibitor protein modulate the sensitivity of the GABA receptor. In addition Grandison and Guidotti have observed specific GABA binding receptors in the pituitary. Thus the previous inability of GABA at "physiological doses" to affect hormone release may involve insensitive GABA receptors. The research outlined below attempts to examine pituitary and hypothalamic GABA function and receptor sensitivity as it relates to the regulation of pituitary hormone secretion. The specificity of GABA action in vitro and in vivo and the interaction between GABA and bendiazepines, a substitute for a putative endogenous ligand, will be examined. Both biological activity, i.e., action on hormone release, and binding studies will be carried out. Correlation of GABA activity and hormone secretion in vivo will be made using GAD activity and GABA reuptake as measures of GABA function. Finally the relationship between GABA and the other neurotransmitters controlling hormone secretion will be studied as part of the major objective: increased understanding of the regulation of anterior pituitary hormone secretion.