CORTICOSTERONE MODULATES GROWTH HORMONE-RELEASING FACTOR AND SOMATOSTATIN IN FETAL-RAT HYPOTHALAMIC CULTURES

It is well known that chronic supraphysiological doses of glucocortico ids (GC) inhibit GH secretion in vivo, and stimulate GH secretion from the somatotropes in vitro. It has been suggested that GC exert an inh ibitory role in the hypothalamus surpassing the GC-positive effect at the somatotrope level. To test the hypothesis that GC can affect growt h hormone-releasing factor (GRF) and somatostatin (SS) at the hypothal amic level, we studied the effect of corticosterone on the immunoreact ive content of GRF (IR-GRF) and SS (IR-SS) in cells and media of fetal hypothalamic cells in culture. After 20 days in culture, cells were i ncubated with serum-free medium containing corticosterone (from 0.3 to 300 nM) for 48 h. Corticosterone had a dual effect on IR-GRF. Concent rations in the range of the glucocorticoid receptor Kd (3 nM) increase d peptide content, whereas higher concentrations (30 and 300 nM) decre ased IR-GRF content in cells and media. Conversely, corticosterone inc reased SS cell content, only at a concentration of 3 nM, inducing a 2- to 3-fold increment in media content with the highest doses (30 and 3 00 nM). These results demonstrated that both GRF and SS are modulated by corticosterone in primary fetal rat hypothalamic cultures. Whereas GRF exhibited a dual response, stimulatory and inhibitory, at low and high corticosterone doses, respectively, SS showed a parallel increase with the corticosterone concentrations.