Effects on the Pituitary-Thyroid Axis and Prolactin Secretion of Single and Repetitive Oral Doses of Thyrotropin-Releasing Hormone (TRH)

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Abstract
The effects of single and repetitive oral doses of synthetic TRH were studied in healthy young men and women. Administration of single doses of TRH, from 2.5 to 160 mg, to each of 18 subjects resulted in increasing maximum increments in serum levels of thyrotropin (TSH), thyroxine (T4, triiodothyronine (T3), and prolactin. The peak incremental responses were these: maximum Δ TSH, 27.1 ± 2.6 μU/ml (to the 80 mg TRH dose); maximum Δ T3, 113 ± 19 ng/100 ml (160 mg); maximum Δ T4, 4.2 ± 0.3 μg/100 ml (160 mg); maximum Δ prolactin in women 46.2 ± 8.2 ng/ml (80 mg); and the maximum Δ prolactin in men, 35.0 ± 3.9 ng/ml (80 mg). Administration of 10 mg of TRH every 8 hr for 22 consecutive doses to each of 9 normal young women resulted in raised mean serum T3 and T4 concentrations, which reached new steady-state levels in 4 and 3 days. The new steady-state T3 levels were approximately 30% higher than the pretreatment T3 level, and the new steady-state T4 levels were approximately 40% higher than the pretreatment T4 level. Concomitant with these increases, the serum TSH response to TRH was markedly inhibited; the responses to the seventh and twenty-second doses were less than 15% of that to the first. The serum prolactin responses to these doses, in contrast, were both approximately 66% of that to the first dose. Chronic TRH excess appears to increase serum prolactin more than serum TSH.

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