DIFFERENTIAL DESENSITIZATION RESPONSE OF THE NEONATAL AND ADULT-RAT SOMATOTROPH TO GROWTH HORMONE-RELEASING HORMONE AND PHORBOL ESTER

Elevated levels of circulating growth hormone (GH) in the perinatal an imal may be caused in part by relative resistance to the desensitizing effects of GH secretagogues. We compared the effects of 4-day exposur e of primary pituitary cell cultures from adult male and 2-day-old rat s to GH-releasing hormone (GHRH; 10 nM) or 12-O-tetradecanoyl-phorbol- 13-acetate (TPA; 1 mu M) on subsequent acute GH response to these secr etagogues. Prolonged exposure to GHRH reduced subsequent GHRH-induced GH release from pituitary cells of both age groups, but the reduction in GH response was significantly less in neonates than adults. In addi tion, GH secretion from neonatal pituitaries rose progressively during each day of GHRH exposure, to reach levels almost 7 times basal; by c ontrast, GH secretion from adult pituitaries increased only transientl y and then declined. Prolonged exposure to TPA reduced the subsequent GH response to TPA equally in neonates and adults, but differentially affected the GH response to GHRH; TPA exposure reduced the GH response to GHRH in neonates, but not in adults. These data suggest a fundamen tal difference between the GH regulatory processes of neonatal and adu lt pituitaries. The ability of the somatotroph to exhibit attenuated G H response on exposure to secretagogue is developmentally regulated, a nd relative resistance of the immature somatotroph to homologous desen sitization by GHRH may contribute to elevated serum GH levels during t he perinatal period.