In vivo studies of somatostatin-14 and somatostatin-28 biosynthesis in rat hypothalamus.

The biosynthesis of somatostatin-14 (SRIF-14) and somatostatin-28 (SRIF-28) was studied in rat hypothalamus after injection of 35S-labeled cysteine into the third ventricle. Cysteine specific activity was quantitated, and found to decline rapidly after injection of the labeled amino acid: less than 0.1% of the injected label remained as free cysteine in the hypothalamus 30 min post injection. Incorporation of label into SRIF-14 and SRIF-28 reached maximum values 8 h post injection, compared with a labeling maximum at 1-2 h for acid-precipitable protein. Within 2 h after [35S]cysteine injection, nearly half of the total labeled hypothalamic SRIF appeared in the medial basal hypothalamus; 24-h post injection this percentage reached approximately 75%. Colchicine administration dramatically reduced the appearance of labeled SRIF in medial basal hypothalamus, but had no apparent effect on the total incorporation of [35S]cysteine into SRIF-14, SRIF-28, or acid-precipitable protein, or on radioimmunoassayable SRIF levels. These results suggest that 1) the technique employed for administering [35S] cysteine delivers the label as a pulse; 2) the timing of the appearance of labeled amino acid in SRIF-14, SRIF-28, and acid-precipitable protein is consistent with initial synthesis of a larger prohormone, followed by conversion to peptide products; and 3) the newly synthesized peptides are rapidly transported to the medial basal hypothalamus by a colchicine sensitive mechanism.