Modulation of thyroid hormone-dependent Na+,K(+)-ATPase induction in cultured human submandibular gland cell lines, HSG cells.

The hormonal regulation of Na+,K(+)-ATPase enzyme activities and induction of the alpha subunit protein of the enzyme in the human submandibular gland (HSG) were studied by use of cultured HSG cells. We treated HSG cells with thyroid hormone, androgen, mineralocorticoid, and glucocorticoid, singly or in combination. 3,5,3'-Triiodothyronine (T3), 5 alpha-dihydrotestosterone (DHT), and aldosterone (Ald) induced neither Na+,K(+)-ATPase enzyme activity nor its protein. On the other hand, dexamethasone (Dex) induced both Na+,K(+)-ATPase enzyme activity and the alpha subunit protein level to 128% of the control. The effects of Dex in combination with either T3 or DHT were similar to the effect of Dex alone. Treatment in combination with Dex and Ald increased the enzyme activity and alpha subunit protein level to 160%, synergistically. These increased Na+,K(+)-ATPase enzyme activities were shown to be dependent on their protein levels induced by the hormones. Contrary to the previous evidence that Na+,K(+)-ATPase of ducts in the salivary gland are thyroid hormone inducible, HSG cells had an insignificant response to thyroid hormone in the present study. Also, Na+,K(+)-ATPase enzyme activity and its alpha subunit protein were not induced by any kind of combined treatments with T3. Furthermore, T3 did not cause intracellular calcium mobilization in HSG cells. In view of all data taken together, we suggest that HSG cells lack the thyroid hormone receptor, which is necessary for Na+,K(+)-ATPase induction in human salivary gland.