Protein kinase C as a mediator of TSH and thyroid autoantibody action.
Although it is well-established that TSH activates a cAMP-dependent pathway in the thyroid follicular cell leading to thyroid hormone synthesis and release, the present review provides new evidence that TSH also activates a non-cAMP-dependent signal transduction system. This cascade involves phosphoinositide (PI) turnover, diacylglycerol accumulation and protein kinase C (PKC) activation. Activation of this pathway leads to an inhibition of differentiated thyroid function in vitro. Recent evidence suggests that TSH can activate both pathways via a single transcription unit. Unlike TSH, TSH-receptor antibodies may selectively activate cAMP with no effects on PI turnover. In contrast, preliminary studies suggest TSH-blocking antibodies may activate PKC. PKC may be an important mediator of TSH and, possibly, thyroid autoantibody action.
Division of Endocrinology, University of Alberta, Edmonton, Canada.
J
J
Ginsberg
D001323:Autoantibodies / Q000276:immunology*; D000242:Cyclic AMP / Q000502:physiology; D006801:Humans; D018828:Immunoglobulins, Thyroid-Stimulating; D010716:Phosphatidylinositols / Q000378:metabolism; D011493:Protein Kinase C / Q000502:physiology*; D011989:Receptors, Thyrotropin / Q000276:immunology / Q000502:physiology; D013961:Thyroid Gland / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D013972:Thyrotropin / Q000494:pharmacology*
D001323:Autoantibodies; D018828:Immunoglobulins, Thyroid-Stimulating; D010716:Phosphatidylinositols; D011989:Receptors, Thyrotropin; D013972:Thyrotropin; D000242:Cyclic AMP; D011493:Protein Kinase C