RENAL-DERIVED SOMATOSTATIN: REGULATION BY GROWTH FACTORS AND cAMP.† 1698

Somatostatin (SS) is known to modulate renal phosphate, water and sodium excretion and tubular gluconeogenesis. We previously reported that freshly isolated human kidney and cultured human proximal tubular epithelial cells(PTEC) and mesangial cells (MC) transcribe SS mRNA; furthermore, PTEC and MC synthesize SS peptide (Regul. Pept., In Press; Pediatr Res 39, Part 2:371A, 1996). These findings raise the possibility that renal-derived SS modulates renal function in an autocrine/paracrine manner. Herein, we further characterize kidney-derived SS mRNA and peptide by Northern blot analysis and enzyme-linked immunoassay. We found that: 1) Human kidney expresses a 750 kb SS mRNA transcript identical in size to SS mRNA expressed in human thyroid carcinoma TT cells. 2) Fetal bovine serum and cAMP stimulate, while epidermal growth factor and hydrocortisone inhibit SS secretion. Insulin, transferrin, and selenium do not alter SS secretion. 3) PTEC secrete both of the major forms of SS, the tetradecapeptide, SS₁₄, and the 28 amino acid peptide, SS₂₈. These two forms of SS can trigger different or even opposite effects, depending on the cell type. Surprisingly, PTEC derived from different donors secrete widely varying proportions of these two peptides. Our findings indicate that renal-derived SS mRNA is processed to the same size as in non-renal cells and that physiologically relevant growth factors modulate PTEC SS secretion. The ability of PTEC to express both SS₁₄ and SS₂₈ expands the possible autocrine/paracrine effects of renal SS production on kidney cell growth, tubular transport and other renal functions.