On the Mechanism of Action of TRF: Effects of Cycloheximide and Actinomycin on the Release of TSH Stimulated in Vitro by TRF and its Inhibition by Thyroxine

Abstract

Hypothalamic TRF stimulates the release of thyrotropin TSH from pituitary tissues incubated in vitro. Cycloheximide (up to 100 [mu]g/ml) or actinomycin D (up to 10 [mu]g/ml) does not inhibit the effects of TRF under conditions in which the antibiotics are shown to inhibit incorporation of 3H-leucine or 3H-uridine. Thyroxine (T4) inhibits the release of TSH normally produced by TRF; cycloheximide prevents or reverses this inhibition. Actinomycin D, in small doses (0.1, 0.2 [mu]g/ml) shown not to interfere with 3H-leucine incorporation, does not reverse the T4-inhibition of the TSH-release but can prevent it. De novo biosynthesis of the protein portion of TSH is not involved in the release of TSH produced by TRF. T4-inhibition of the effects of TRF is effected through one or several intermediate substances, the synthesis of which is induced by T4 and can be modified by cycloheximide or actinomycin D. Several hypotheses are presented to relate these observations to the effects of elevated K+ and Ca++ requirement on the stimulation by TRF or TSH release in vitro.