The objectives of this project are to develop the techniques to study brain regulation of growth hormone using sheep as a model.
Specific aims of this project are: (1) develop and validate stereotaxic methods for placement of electrodes, infusion cannulae and push-pull cannulae in the arcuate nucleus (ARC) ventromedial nucleus (VMN) periventricular nucleus (PV) and median eminence (ME); (2) map these regions by providing an electrical stimulus and determining the change in concentration of plasma GH; (3) determine the relationships between plasma GH and ME release of growth hormone releasing factor (GRF) and somatostatin (SRIF). The methods involve surgical placement of guide cannulae into the ARC, VMN, PV and ME of anesthetized ewes. An electrical stimulus will be applied to either the ARC, VMN or the PV. Jugular vein concentrations of GH will be quantified and compared to push-pull cannula perfusates from the ME quantified for SRIF or GRF. Collections will begin 1 hour before and 2 hours following a stimulus. The sheep will be allowed to rest for 3 weeks before the application of a stimulus to another nucleus or the use of a different intensity, duration or frequency of a stimulus to a particular nucleus. Hormone responses will be analyzed by analysis of variance and regression heterogeneity. The sheep has not been used in studies such as these but has advantages over other nonprimate models. These studies should provide a basis for future proposals to study the mechanisms by which the central nervous system integrates the control of GH secretion under normal conditions and under conditions of GH deficiency or excesses such as found in dwarfism or acromegaly.
| Sartin, J L; Bartol, F F; Kemppainen, R J et al. (1988) Modulation of growth hormone-releasing factor stimulated growth hormone secretion by plasma glucose and free fatty acid concentrations in sheep. Neuroendocrinology 48:627-33 |
