Inhibition of thyrotrophin-releasing hormone responsiveness by physiological concentrations of thyroid hormones in the cultured rat pituitary gland.

Diced quarter anterior pituitaries from mature females Wistar rats were cultured in synthetic medium with or without added serum. Using each culture as its own control, the thyrotrophin-releasing hormone (TRH) dose-thyrotrophin (TSH) response characteristics of both media were similar; significant TSH secretion being stimulated at TRH doses around 1-5 X 10(-9) mol/l. During days 1-3 of culture, basal TSH secretion fell significantly but TRH responsiveness was unchanged. Neither tri-iodothyronine (T3) nor thyroxine (T4) influenced basal TSH secretion. In both culture media inhibition of TRH responsiveness was demonstrated with concentrations of T3 and T4 within the ranges 1-5 X 10(-12) to 1-5 X 10(-9) mol/l for T3 and 6-5 X 10(-10) to 6-5 X 10(-7) mol/l for T4. Equivalent inhibition was accompanied by similar T3 concentrations whether T3 or T4 supplements were used, suggesting that T4 itself has no feedback action. The similar concentrations of T3 required to inhibit TRH responsiveness in media either with or without serum suggest that the pituitary is responsive not only to free but also to total thyroid hormone concentrations, since serum-free medium contains no thyroid hormone-binding protein.