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  • Title: Release of thyrotropin and prolactin by a thyrotropin-releasing hormone (TRH) precursor, TRH-Gly: conversion to TRH is sufficient for in vivo effects.
    Author: Pekary AE, Stephens R, Simard M, Pang XP, Smith V, DiStefano JJ, Hershman JM.
    Journal: Neuroendocrinology; 1990 Dec; 52(6):618-25. PubMed ID: 2126612.
    Abstract:
    The mechanism by which TRH-Gly (pGlu-His-Pro-Gly), a biosynthetic precursor of thyrotropin-releasing hormone (TRH, pGlu-His-Pro-NH2), stimulates pituitary thyrotropin (TSH) and prolactin release has been studied in urethane-anesthetized 2-month-old (250 g) male Sprague-Dawley rats and in vitro with GH3 cells, a rat anterior pituitary tumor cell line. We used specific radioimmunoassays to measure TRH-Gly and TRH levels in rat cortex, hypothalamus, medulla, eyes and whole blood as a function of the intracisternal (IC) dose of TRH and TRH-Gly administered 40 min prior to sacrifice. IC injection of 1.0 mg of TRH-Gly led to a significant (p less than 0.005) increase in the TRH levels in hypothalamus, medulla and blood. The relative potency of IC and intracardiac (IK) TRH and TRH-Gly release of rat TSH was compared by radioimmunoassay and further refined using estimates based on in vivo kinetics of TRH-Gly alpha-amidation. The binding of TRH-Gly to the plasma membrane receptors for TRH on GH3 cells was also investigated. In regard to TSH release, TRH-Gly given IC had only 0.042% of the potency of TRH given IC and was consistent with its rate of IC alpha-amidation. IK TRH-Gly had 0.16% of the potency of IK TRH of TSH release and was also consistent with its rate of intravascular conversion to TRH. The mean peak TSH response occurred at 20 min after IC TRH-Gly or IC TRH injection but the post-peak decline was slower for IC TRH-Gly.(ABSTRACT TRUNCATED AT 250 WORDS)
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