Modulation of thyroglobulin release by dog thyroid slices.

Area of Science:

• Endocrinology
• Cell Biology
• Molecular Biology

Background:

• Nonbutanol-extractable 131I (NBE131I), primarily thyroglobulin (Tg), release from dog thyroid slices is stimulated by TSH.
• This NBE131I (Tg) release serves as an in vitro model for thyroglobulin secretion.

Purpose of the Study:

• To further characterize the mechanisms underlying TSH-stimulated NBE131I (Tg) release in dog thyroid slices.
• To investigate the role of cyclic AMP (cAMP), cellular signaling pathways, and intracellular processes in Tg secretion.

Main Methods:

• Utilized dog thyroid slices incubated in vitro.
• Stimulated NBE131I (Tg) release using TSH, forskolin, and (Bu)2cAMP.
• Investigated the effects of carbamylcholine, atropine, methimazole, perchlorate, monensin, chloroquine, cytochalasin B, and EGTA on NBE131I (Tg) release.
• Assessed the formation of apical pseudopods and release of butanol-extractable 131I (BE131I, T4, T3, iodide).

Main Results:

• TSH-stimulated NBE131I (Tg) release is mediated by cAMP, similar to BE131I release.
• Carbamylcholine inhibited TSH-, (Bu)2cAMP-, and forskolin-stimulated NBE131I (Tg) release at a step beyond cAMP, an effect reversed by atropine.
• NBE131I (Tg) release occurred independently of apical pseudopod formation, intralysosomal Tg hydrolysis, or the escape of undegraded Tg from lysosomes.
• Cytochalasin B increased NBE131I (Tg) release, while EGTA enhanced it by removing Ca2+.

Conclusions:

• TSH-stimulated NBE131I (Tg) release in dog thyroid slices is cAMP-dependent and involves a signaling pathway inhibited by carbamylcholine.
• The secretion of Tg does not appear to involve neosynthesis, apical pseudopod formation, or lysosomal escape.
• These findings elucidate a distinct mechanism for thyroglobulin secretion in the thyroid gland.