Regulation of growth hormone release: evidence against negative feedback in rat pituitary cells.

To determine if the anterior pituitary gland is the site of negative feedback inhibition of GH release, we studied the effect of GH and multiplication-stimulating activity (MSA), a member of the somatomedin family, on isolated rat anterior pituitary cells in primary culture. The effect of GH was examined in two ways: 1) by adding to the cultures human GH (10 ng/ml to 20 microgram/ml) which was biologically active in the rat but not cross-reactive in the rat GH (rGH) RIA, and 2) by comparing rGH secretion in cultures of different cell densities. No suppression of either basal or prostaglandin E1-stimulated rGH release was found. An enhancement observed in serum-free conditions at high human GH concentrations was interpreted as a nonspecific response to protein, because bovine serum albumin produced the same effect. When added in the presence of serum, MSA (1--500 ng/ml) had no effect on rGH secretion. In the absence of serum, there were 71% and 30% increases in the basal and prostaglandin E1-stimulated rates of hormone release, respectively, possibly attributable to a trophic effect of MSA. Six other hormones having structural or functional similarity to either GH or somatomedin also failed to inhibit rGH secretion. Our results do not support the hypothesis that GH or somatomedin exerts a negative feedback effect on GH release directly on the anterior pituitary gland. Most likely, the hypothalamus or a higher brain center is the site for such regulation.