The effects of hydrocortisone and RU486 (mifepristone) on iodide uptake in porcine thyroid cells in primary culture.
The effects of hydrocortisone on iodide uptake and DNA synthesis were studied in porcine thyroid cells cultured in phenol red-free medium supplemented with low concentrations (0-1%) of charcoal-stripped fetal calf serum. Hydrocortisone dose-dependently stimulated TSH-induced iodide uptake at physiological concentrations (1-1000 nM), and the minimum detectable dose was 33 nM hydrocortisone. Treatment of thyroid cells with hydrocortisone for 72 h increased cAMP production stimulated by TSH. In addition, this stimulatory effect of hydrocortisone was observed when iodide uptake was induced with 0.25 mM 8-bromo-cAMP. These results suggest that hydrocortisone stimulates iodide uptake, influencing cAMP production and post-cAMP pathways. The synthetic glucocorticoid antagonist RU486 alone had no effect on iodide uptake in porcine thyroid cells; however, along with TSH, RU486 a weak agonist activity. As a glucocorticoid antagonist, RU486 inhibited the stimulatory actions of hydrocortisone on iodide uptake in combination with TSH and also with 8-bromo-cAMP, suggesting a specific effect of hydrocortisone mediated by a glucocorticoid receptor. The effect of hydrocortisone on thyroid cell multiplication was also studied. Hydrocortisone decreased [3H]thymidine incorporation into DNA slightly but not significantly when the cells were treated with 100 ng/ml insulin-like growth factor-I and hydrocortisone. In summary, it has been demonstrated that hydrocortisone directly stimulated the function of porcine thyroid cells at physiological concentrations, by using a glucocorticoid receptor and by affecting cAMP pathways. The data that RU486 inhibited iodide uptake induced by hydrocortisone and TSH propose that monitoring of thyroid function may be necessary if RU486 is been used for a long time.
Second Department of Internal Medicine, Asahikawa Medical College, Japan.
Y
Y
Takiyama
H
H
Tanaka
Y
Y
Takiyama
I
I
Makino
D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006854:Hydrocortisone / Q000494:pharmacology*; D007454:Iodides / Q000493:pharmacokinetics*; D015735:Mifepristone / Q000494:pharmacology*; D013552:Swine / Q000378:metabolism*; D013936:Thymidine / Q000378:metabolism; D013961:Thyroid Gland / Q000166:cytology* / Q000378:metabolism* / Q000502:physiology; D013972:Thyrotropin / Q000494:pharmacology; D014316:Tritium
D007454:Iodides; D014316:Tritium; D015735:Mifepristone; D013972:Thyrotropin; D004247:DNA; D000242:Cyclic AMP; D013936:Thymidine; D006854:Hydrocortisone