Somatostatin partially reverses desensitization of somatotrophs induced by growth hormone-releasing factor

Abstract

The effect of somatostatin on GH-releasing factor (GRF)-induced desensitization of somatotrophs was studied in vitro. Primary cultures of rat anterior pituitary cells pretreated for 4 or 18 h with GRF(1-40) (100 nmol/l) showed a 50% or greater reduction in maximal GH release when rechallenged with 10 nmol GRF/l. Rechallenge GRF dose-response curves were either very flat, making accurate measurement of the dose giving 50% maximum stimulation (ED50) impossible, or the ED50 concentration was increased from 0.3 nmol/l (untreated) to 2 nmol/l (GRF pretreated). Although GRF pretreatment reduced cellular GH content by 40-50%, correction for this did not restore GRF responsiveness measured in terms of maximal GRF-stimulated/unstimulated GH release (maximal/basal ratio), or the GRF ED50 concentration. Maximal/basal GH release per 4 h from GRF-pretreated cells was reduced when cells were rechallenged with forskolin (5 mumol/l) or calcium ionophore (A23187; 10 mumol/l), to the same extent as when rechallenged with 10 nmol GRF/l. Although this might be explained by a reduction in the pool of releasable GH, an alternative explanation is that pretreatment with GRF d disrupts the GH release mechanism(s) at a common step(s) beyond cyclic AMP generation and Ca2+ influx. Co-incubation of cells with somatostatin and GRF (100 nmol/l) partially reversed the desensitizing action of GRF during both 4- and 18-h pretreatments in a dose-dependent manner, with 1 mumol somatostatin/l being most effective. Maximal GRF (100 nmol/1-stimulated/basal GH release was 4.4 +/- 1.0 (mean +/- S.E.M., n = four experiments), 1.55 +/- 0.09 and 2.43 +/- 0.1 for control, GRF-pretreated (4 h) and GRF plus somatostatin-pretreated cells respectively.(ABSTRACT TRUNCATED AT 250 WORDS)