Dexamethasone stimulates thyrotropin-releasing hormone production in a C cell line.
The hypothalamic peptide hormone TRH is also found in other tissues, including the thyroid. While TRH may be regulated by T3 in the hypothalamus, other regulators of TRH have not been identified and the regulation of TRH in nonhypothalamic tissues is unknown. We recently demonstrated the biosynthesis of TRH in the CA77 neoplastic thyroidal C cell line. We studied the regulation of TRH by dexamethasone in this cell line because glucocorticoids have been postulated to inhibit TSH secretion by decreasing TRH in the hypothalamus. Furthermore, TRH in the thyroid inhibits thyroid hormone release. Thus by regulating thyroidal TRH, glucocorticoids could also directly affect thyroid hormone secretion. Treatment of CA77 cells for 4 days with dexamethasone produced dose-dependent increases in both TRH mRNA and cellular and secreted TRH. Increases in TRH mRNA and peptide levels could be seen with 10(-9) M dexamethasone. A 4.8-fold increase in TRH mRNA and a 4-fold increase in secreted peptide were seen with 10(-7) M dexamethasone. Dexamethasone treatment did not increase beta-actin mRNA levels or cell growth. These results suggest that glucocorticoids may be physiological regulators of TRH in normal C cells. In addition to their inhibitory effects on TSH, glucocorticoids may decrease thyroid hormone levels by increasing thyroidal TRH. Since the glucocorticoid effects on C cell TRH are the converse of what is expected for hypothalamic TRH, glucocorticoid effects in these two tissues may be mediated by different regulators.
Tavianini
M A
MA
Geriatric Research, Education, and Clinical Center, American Lake Veterans Administration Medical Center, Tacoma, Washington 98493.
Gkonos
P J
PJ
Lampe
T H
TH
Roos
B A
BA
D000199:Actins / Q000235:genetics; D000818:Animals; D015152:Blotting, Northern; D002116:Calcitonin / Q000032:analysis; D003907:Dexamethasone / Q000494:pharmacology*; D005786:Gene Expression Regulation; D012313:RNA / Q000032:analysis / Q000302:isolation & purification; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D013973:Thyrotropin-Releasing Hormone / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D000199:Actins; D012333:RNA, Messenger; D013973:Thyrotropin-Releasing Hormone; D012313:RNA; D003907:Dexamethasone; D002116:Calcitonin