Inhibition of thyrotropin-induced DNA synthesis in thyroid follicular cells by microinjection of an antibody to the stimulatory G protein of adenylate cyclase, G(s)

Thyrotropin (TSH) is an important regulator of thyroid follicular cells. While its role in the maintenance of differentiated functions is undisputed, its role as a mitogen is less clear. TSH induces DNA synthesis and cell proliferation in some cells, while in others, TSH is mitogenic only in the presence of additional growth factors such as insulin-like growth factor-1. TSH causes elevations in intracellular cAMP and is thought to utilize this second messenger system in its mitogenic action. We studied TSH as a mitogen in Wistar rat thyroid cells (WRT) (Brandi, M. L., Rotella, C. M., Mavilia, C., Franceschelli, F., Tanini, A., and Toccafondi, R. (1987) Mol. Cell. Endocrinol. 54, 91-103) and examined the role of the guanine nucleotide binding protein, G(s), in its mitogenic action. WRT cells synthesized DNA in response to TSH and elevations in cAMP. In addition, TSH caused a rapid stimulation of an indicator gene whose expression is regulated by cAMP response elements. Following microinjection of an inhibitory polyclonal antibody raised against the G(s) protein, both TSH-induced changes in gene expression and DNA synthesis were significantly reduced. These results demonstrate that virtually all of the mitogenic action of TSH is transduced through the G(s) protein in WRT cells, presumably through the regulation of adenylate cyclase. Whether all or only part of TSH action is mediated by cAMP and the cAMP-dependent protein kinase remains to be determined.