Affiliation:
1. Division of Endocrinology, Department of Medicine, Brown University/Rhode Island Hospital, Providence, Rhode Island 02903
2. Institut für Zellbiochemie, Universitätskrankenhaus Eppendorf, Universität Hamburg (T.O.B.), 22529 Hamburg, Germany
Abstract
Abstract
Disulfiram (Dis), an inhibitor of peptidyl-glycine α-amidating monooxygenase, the enzyme responsible for the production ofα -amidated peptides from their immediate, glycine-extended precursors was used to investigate the paracrine effects of TRH on anterior pituitary (AP) hormone secretion. It reduces the production of TRH without directly affecting the classical pituitary hormones, none of which is amidated.
Dis (8 μm) decreased the accumulation of TRH accompanied by an equimolar increase in TRH-Gly levels, indicating that pro-TRH biosynthesis persisted. TRH and TSH release into the medium was significantly lowered, whereas other pituitary hormones were unaffected. In contrast, dexamethasone (10 nm), which up-regulates TRH gene expression in this system, increased TRH (+89.5%) and TSH (+61.3%) secretion. The combination of dexamethasone and Dis further diminished the release of TRH (−73%) and TSH (−40.3%) observed with Dis alone, indicating that TRH synthesized within the AP regulates TSH secretion.
Dis significantly elevated prepro-TRH (25–50) and pro-TRH messenger RNA levels, suggesting that reduced TRH formation leads to increased pro-TRH biosynthesis and that TRH regulates its own secretion. Thus, TRH synthesized by cultured AP cells not only stimulates TSH release through a paracrine effect, but has a negative feedback on its own biosynthesis by an autocrine mechanism.
Reference48 articles.
1. TRH prohormone: biosynthesis, anatomic distribution, and processing.;Jackson;Front Neuroendocrinol,1990
2. Structure of the gene encoding rat thyrotropin releasing hormone.;Lee;J Biol Chem,1988
3. Distribution of thyrotropin-releasing hormone (TRH) and precursor peptide (TRH-Gly) in adult rat tissues.;Fuse;Endocrinology,1990
4. Identification in pituitary tissue of a peptide α-amidation activity that acts on glycine-extended peptides and requires molecular oxygen, copper, and ascorbic acid.;Eipper;Proc Natl Acad Sci USA,1983
5. Amidation of joining peptide, a major pro-ACTH/endorphin-derived product peptide.;Eipper;J Biol Chem,1986
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