The Somatostatin Analogue Octreotide Modulates Iodothyronine Deiodinase Activity and Pituitary Neuromedin B

Abstract

Somatostatin inhibits growth hormone and thyrotropin (TSH) secretion. It also 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 neuromedin B (NB), an autocrine inhibitor of TSH secretion, which is positively regulated by thyroid hormones. Euthyroid or hypothyroid rats were sacrificed at different times after a single subcutaneous injection of OCT (1 microg/kg body weight [BW]). D1 and D2 activities were measured by the release of 125I from 125I reverse triiodothyronine (rT3) under different assay conditions. NB, TSH, T3, and thyroxine (T4) were quantitated by radioimmunoassay (RIA). In euthyroid rats, liver and pituitary D1 activities were decreased (50%) 6 hours after OCT injection; pituitary D2 and NB remained unchanged. In hypothyroid rats, OCT increased near to the level of normal rats both pituitary D1 activity (but not liver) and NB content, at 24 hours and at 6 and 24 hours, respectively (p < 0.05). Pituitary D2, greatly increased by hypothyroidism, showed a small (25%) but significant reduction at 3 hours, persisting at 24 hours (p < 0.01), although it remained higher than that of euthyroid control. Serum thyroid hormones were not affected by OCT injection. The results show that octreotide acutely regulates pituitary deiodinases and NB content, both representing mechanisms that potentially can contribute to somatostatin and octreotide actions on pituitary growth hormone (GH) and TSH secretion and to modulate these cells sensitivity to thyroid hormone action.

Different responses to chronic somatostatin analogues in patients with central hyperthyroidism

“…Similar TSH inhibitions have been reported after acute SMS test in acromegalic patients 26,27 . The lack of FT4 variations is indeed due to the long half‐life of T4, while the slight reduction in FT3 circulating levels is due to both its shorter half‐life and a possible inhibitory action on deiodinase activity of somatostatin analogues 28 …”

“…26,27 The lack of FT4 variations is indeed due to the long half-life of T4, while the slight reduction in FT3 circulating levels is due to both its shorter half-life and a possible inhibitory action on deiodinase activity of somatostatin analogues. 28 On the contrary, the thyroid hormone response to 2-month Octreotide-LAR administration was significantly different in the two groups of patients. In particular, no significant variations in serum FT3 or FT4, as well as TSH, concentrations were seen in all PRTH patients after 28 or 56 days of treatment, whereas significant reduction or normalization of free thyroid hormones were seen in seven of eight patients with TSH-oma, being criteria for response the normalization of free thyroid hormone levels or at least a reduction of FT3/FT4 levels greater than 30% vs. baseline values.…”

Regulação da síntese e secreção de tireotrofina

“…O hipotireoidismo está associado a baixas concentrações de NB, enquanto o hiper- tireoidismo aumenta sua concentração hipofisária, assim como a expressão do seu RNAm (32,33). Análogos da somatostatina, como o octeotride, que inibem o TSH, aumentam a concentração de NB (34). A NB encontra-se elevada em situações experimentais associadas com a redução da liberação de TSH, tais como jejum e diabetes mellitus (35), enquanto o TRH e o frio inibem sua expressão hipofisária (36).…”

The Autocrine/Paracrine Regulation of Thyrotropin Secretion

“…Hypothyroidism decreases while hyperthyroidism increases the rat pituitary content of NB and its mRNA (101,100). Octreotide, a long-acting somatostatin analogue, which has an inhibitory action on TSH release, has been shown to increase pituitary NB content (103). Experimental situations associated with reduced TSH release, such as fasting and diabetes mellitus, are also associated with increment in the pituitary content of NB (104).…”