GENE-TRANSCRIPTION OF RECEPTORS FOR GROWTH HORMONE-RELEASING PEPTIDE AND SOMATOSTATIN IN HUMAN PITUITARY-ADENOMAS

Growth hormone (GH)-releasing peptides (GHRP) or secretagogs (GHS) con stitute a family of synthetic compounds with potent and specific GH re leasing activity. The receptor (GHS-R) has recently been cloned even t hough the endogenous ligand remains to be identified. GHRPs act both a t the hypothalamic and the pituitary level through mechanisms involvin g amplification of GH-releasing hormone activity and functional somato statin antagonism. In the present study we examined the co-expression of messenger RNA (mRNA) for GHS-R and all 5 somatostatin receptor subt ypes (sstr 1-5) in 28 human pituitary tumors by RT-PCR. GHS-R transcri ption was detected in 11 out of 12 somatotroph adenomas and in 2 out o f 2 prolactinomas, whereas GHS-R expression was detected in only 2 out of 14 clinically nonfunctioning adenomas (NFPA), and no expression wa s seen in the only ACTH secreting adenoma. Almost all tumors expressed sstr 2 mRNA (n = 24), whereas only 1 tumor expressed sstr 4 mRNA. The expression of sstr 3 mRNA was inversely associated with GHS-R express ion (P < 0.001), which could be attributed to a high prevalence of sst r 3 expression in NFPA. This study suggests that GHS-R expression is p redominantly observed in somatotroph adenomas and much less so in NFPA . Moreover, the presence of a distinct pattern of somatostatin recepto r subtype co-expression is suggested, which may provide a molecular ba sis for the complex interaction between GHRPs and somatostatin.