Studies on Somatotropin-release Inhibiting Factor

Abstract

Recently, Guillemin and his coworkers (1973) presented a tetradecapeptide structure for somato- tropin-release inhibiting factor (SRIF) and reported that the synthetic replicate corresponding to the proposed sequences possessed identical activities with that of natural purified SRIF. We have perform- ed the synthesis of this peptide and examined its effects on GH release and cyclic AMP formation in rat anterior pituitary gland. The concentration of cyclic AMP in tissue was determined by competi- tive protein binding assay and GH in the medium or in plasma were assayed using rat GH radio- immunoassay kit provided by NIAMDD. Synthetic SRIF (10ng/ml) decreased significantly the basal level of cyclic AMP in rat anterior pituitary incubated in KRB buffer containing glucose (1mg/ml) and theophylline (10^-2M) and showed marginal inhibition of GH release from the pituitary gland into the incudation medium. Higher dose of synthetic SRIF was needed to produce significant inhibi- tion of GH release from the gland into the medium. Stimulating effects of PGEi on both cyclic AMP formation and GH release in rat anterior pituitary were also suppressed by the addition of synthetic SRIF to the incubation medium. In vivo experiments, synthetic SRIF intravenously injected to the rat showed the inhibitory action to the PGE1 or Na pentobarbital stimulaton of GH release. However, not only the stimulation of GH release and of cyclic AMP production in rat anterior pituitary gland by stimulating substance of GH release, but also the cyclic AMP production induced by synthetic TRH or rat hypothalamic extract were inhibited by SRIF.
These results suggest that synthetic SRIF as well as hypothalamic releasing hormones may act through adenylate cyclase-cyclic AMP system in rat anterior pituitary, although the action of synthetic SRIF seems to be more complicate.