SOMATOSTATIN AND GROWTH HORMONE-RELEASING HORMONE IN NORMAL AND TUMORAL HUMAN BREAST-TISSUE - ENDOGENOUS CONTENT, IN-VITRO PULSATILE RELEASE, AND REGULATION

Endogenous production of SRIH and GHRH was analysed in human breast ti ssue. SRIH precursor (pro-SRIH) was identified after Sephadex G-50 fil tration of acetic acid extracts of normal and tumoral human breast sam ples. SRIH-(1-14) or -(1-28) could not be detected in breast tissue, w hereas the immunoreactive SRIH released in vitro was characterized as SRIH-(1-28). Endogenous production of GHRH was assessed by identificat ion of GHRH messenger ribonucleic acid by PCR followed by sequencing o f the amplified complementary DNA and by high performance liquid chrom atographic characterization of immunoreactive GHRH contained in the ti ssue and released in vitro. There were no differences in pro-SRIH or G HRH-(1-44) tissue contents between normal and tumoral samples. The rel ease of both peptides was evidenced in perifusion and static incubatio n. Perifusion of normal breast tissue (n = 3) showed pulsatile release of SRIH and GHRH. Perifusion of tumors (n = 4) showed SRIH release in 50% of the cases. SRIH release was pulsatile in one case. GHRH releas e was observed in the four tumoral samples analysed, but was pulsatile in only one case. In static incubation, tumors (n = 6) secreted 13 ti mes more GHRH than did normal samples (n = 3; 383 +/- 92 vs. 29.6 +/- 4.6 fmol/mg protein; P < 0.05). Stimulation of GHRH release by exogeno us SRIH was observed only with the normal tissue. Together these data provide evidence for the existence of local production of SRIH and GHR H by human breast. Hypersecretion of GHRH by breast tumors indicates t hat this peptide could play a role in maintaining epithelial cell prol iferation as is the case for other peptides produced locally.