Stimulation of Human Thyroid Growth Via the Inhibitory Guanine Nucleotide Binding (G) Protein Gi: Constitutive Expression of the G-Protein α Subunit Giα-1in Autonomous Adenoma

The α subunits of the stimulatory and inhibitory G proteins, Gsαand Giα, activate transmembrane-signaling systems involved in the control of cell proliferation. We have investigated the pattern of expression of Giαsubtypes and Giα-mediated proliferative responses in the human thyroid. Human thyroid membranes contain two subtypes of Giα, Giα-1and Giα-2, as assessed by using specific antibodies. The expression of Giα-1is under tight control by thyrotropin in vivo and in primary cultures of thyroid epithelial cells. In contrast, Giα-1is expressed in the absence of thyrotropin in thyroid autonomous adenoma, an endocrine-active tumor, and its levels are not regulated by thyrotropin in thyroid epithelial cells prepared from these tumors. If thyroid epithelial cells are treated with pertussis toxin to block signal transduction via Gi, the mitogenic response to serum factors is reduced. These observations demonstrate that Gisubtypes transmit growth stimuli in the human thyroid. The constitutive expression of Giα-1in autonomous adenoma may allow for the unregulated stimulation of thyroid cell proliferation by a yet unidentified signaling pathway and, thus, be causally related to autonomous growth of thyroid cells.