The somatostatin analogue octreotide modulates iodothyronine deiodinase activity and pituitary neuromedin B

Somatostatin inhibits growth hormone and thyrotropin (TSH) secretion. It al so enhances the inhibitory effect of thyroid hormone (TH) on TSH by poorly understood mechanisms. We investigated the acute effect of the long-acting somatostatin analogue, octreotide (OCT), on anterior pituitary type 1 (D1) and 2 (D2) deiodinase activity, on liver D1, and on pituitary content of ne uromedin B (NB), an autocrine inhibitor of TSH secretion, which is positive ly regulated by thyroid hormones. Euthyroid or hypothyroid rats were sacrif iced at different times after a single subcutaneous injection of OCT (1 mu g/kg body weight [BW]). D1 and D2 activities were measured by the release o f I-125 from I-125 reverse triiodothyronine (rT(3)) under different assay c onditions. NE, TSH, TSI and thyroxine (T-4) were quantitated by radioimmuno assay (RIA). In euthyroid rats, liver and pituitary D1 activities were decr eased (50%) 6 hours after OCT injection; pituitary D2 and NE remained uncha nged. In hypothyroid rats, OCT increased near to the level of normal rats b oth pituitary D1 activity (but not liver) and NE content, at 24 hours and a t 6 and 24 hours, respectively (p < 0.05). Pituitary D2, greatly increased by hypothyroidism, showed a small (25%) but significant reduction at 3 hour s, persisisting at 24 hours (p < 0.01), although it remained higher than th at of euthyroid control. Serum thyroid hormones were not affected by OCT in jection. The results show that octreotide acutely regulates pituitary deiod inases and NE content, both representing mechanisms that potentially can co ntribute to somatostatin and octreotide actions on pituitary growth hormone (GH) and TSH secretion and to modulate these cells sensitivity to thyroid hormone action.