Abstract
Diazomethyl ketone and chloromethyl ketone analogs of thyrotropin releasing hormones have been synthesized and studied for their inhibitory effects on thyrotropin releasing hormone-induced release of radioactive 125I-labelled hormones from the thyroid gland of eight-week old male Long-Evans rats. When Long-Evans rats were pretreated with thyrotropin releasing hormone diazomethyl ketone (TRH-DMK) or the chloromethyl ketone derivative (TRH-CMK), a dose-related inhibition of thyrotropin releasing hormone-induced 125I release was observed which could be partially reversed by thyrotropin stimulating hormone (TSH). The diazomethyl ketone was a more effective inhibitor than the chloromethyl ketone. These compounds may act as an active-site directed antagonists whose effects are unique to the hypothalamo-pituitary-thyroid system.
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