The overall objective of this research is to localize and determine the functional organization of brain structures which control the secretion of the anterior pituitary; attention will focus on somatostatin (SRIF) neurons which inhibit the secretion of growth hormone (GH) and thyroid-stimulating hormone (TSH).
The specific aims are to: 1) Test the hypothesis that the SRIF neurons which inhibit GH and TSH secretion under nonstress and stress conditions reside in groups that are anatomically and functionally separate; 2) Locate the SRIF neurons essential for GH responses to feedback and other physiological signals, including response to stress; 3) Test the hypothesis that SRIF neurons play a major role in producing the marked species differences that characterize the control of GH secretion. In the first series of studies, in vivo and in vitro approaches will be used to identify and localize the neural structures that inhibit GH and TSH secretion under nonstress and stress conditions, using ablative procedures (electrolytic and ibotenic acid lesions). and to study the effects of such lesions on SRIF release as assessed in vivo by push-pull perfusion and in vitro by perifusion of preoptic- basal hypothalamic (PO-BH) tissue. In situ hybridization and immunocytochemistry will also be used to localize the SRIF neurons involved. The next series of studies will use most of the same methods to locate the SRIF neurons essential for GH/SRIF responses to feedback and other physiological signals. Emphasis will be placed on the organization of neural circuits that inhibit GH secretion in response to stress and the role of corticotropin releasing factor in this regard. A final series of studies will use some of the same in vivo and in vitro approaches to investigate the bases for the remarkable species differences that characterize the control of GH secretion; in addition to rats, these experiments will involve hamsters and a few rhesus macaques. The latter will be used only for in vitro perifusion of PO-BH tissues obtained as they become available from experiments of others. These projects should provide new and useful information about the organization and function of brain structures that control GH secretion and growth.
