Synthetic thyrotropin-releasing hormone (TRH) was administered by single intravenous injection to 79 healthy male volunteers and seven patients with secondary hypothyroidism. Plasma thyrotropin (TSH), growth hormone (GH), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and cortisol concentrations were measured before and after TRH administration. In the normal subjects, the mean base-line TSH concentration was 4.5 μU per milliliter. Plasma TSH rose promptly to a peak of 14.0 μU per milliliter 30 minutes after TRH injection. No rises were observed in the other plasma hormones measured. In the patients with secondary hypothyroidism, TRH failed to elevate TSH. No evidence of toxicity and no serious side effects were seen after TRH administration. TRH is a potent and nontoxic stimulator of TSH release in man and is a useful diagnostic compound in testing pituitary TSH reserve. The availability of TRH now makes possible the recognition of “hypothalamic” hypothyroidism. The concentration of thyroid hormones in blood is finely controlled by a dynamic control system involving the hypothalamus and the pituitary and thyroid glands. Thyrotropin-releasing hormone (TRH) from the hypothalamus stimulates the release of pituitary thyrotropin (TSH), the major regulator of thyroid-hormone formation and release. Thyroid hormones, in turn, restrain TSH secretion by blocking TRH action at the anterior-pituitary level.1 Purification of TRH from porcine hypothalami by Schally and his collaborators,2 and from ovine hypothalami by Guillemin and his co-workers,3 revealed that TRH in both species is a tripeptide whose structural formula is L-pyroglutamyl-L-histidyl-L-prolineamide. Available evidence indicates that human TRH.
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