Hydrogen Sulfide Promotes Thyroid Hormone Synthesis and Secretion by Upregulating Sirtuin-1

Area of Science:

• Endocrinology
• Molecular Biology
• Gasotransmitter Signaling

Background:

• Hypothyroidism can result from disrupted thyroid hormone synthesis and secretion by thyrocytes.
• Hydrogen sulfide (H2S), a gas signaling molecule, influences various physiological processes, often by upregulating sirtuin-1 (SIRT1).

Purpose of the Study:

• To investigate if H2S enhances thyroid hormone synthesis and secretion through SIRT1 upregulation.
• To determine the role of H2S in regulating key proteins involved in thyroid hormone production and transport.

Main Methods:

• Assessed H2S-generating enzyme expression in human thyroid tissues using RT-PCR and immunohistochemistry.
• Measured serum H2S levels in hypothyroid patients and euthyroid controls using selective sensors.
• Evaluated thyroid hormone levels (FT4, TT4, TSH) in hypothyroid rats treated with an H2S donor (NaHS).
• Examined the effect of NaHS and a SIRT1 inhibitor (EX527) on thyroid hormone synthesis/secretion proteins (TPO, NIS, Pendrin, MCT8) in human thyrocytes.

Main Results:

• Serum H2S levels were significantly lower in hypothyroid patients and positively correlated with thyroid hormone levels (FT3, FT4, TT3, TT4).
• NaHS administration improved thyroid function in hypothyroid rats.
• In human thyrocytes, NaHS increased the expression of TPO, NIS, Pendrin, and MCT8 in a dose-dependent manner.
• SIRT1 inhibition with EX527 blocked the NaHS-induced upregulation of these proteins and reduced FT4 secretion.

Conclusions:

• Hydrogen sulfide (H2S) is primarily generated by CBS in thyrocytes.
• Reduced serum H2S levels are associated with hypothyroidism.
• H2S promotes thyroid hormone synthesis and secretion by upregulating SIRT1 and increasing the expression of key regulatory molecules.