Thyrotropin-releasing hormone and phorbol esters induce phosphatidylcholine synthesis in GH(3) pituitary cells: Evidence for stimulation via protein kinase C Journal Article


Author: Kolesnick, R. N.
Article Title: Thyrotropin-releasing hormone and phorbol esters induce phosphatidylcholine synthesis in GH(3) pituitary cells: Evidence for stimulation via protein kinase C
Abstract: Phorbol esters have been shown to stimulate phosphatidylcholine synthesis via the CDP-choline pathway. The present study compares the effects of phorbol esters and thyrotropin-releasing hormone (TRH) on phosphatidylcholine metabolism in GH3 pituitary cells. In a previous study (Kolesnick, R.N., and Paley, A.E. (1987) J. Biol. Chem. 262, 9204-9210), the potent phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA) induced time- and concentration-dependent incorporation of 32P(i) and [3H]choline into phosphatidylcholine in short-term labeling experiments. In this study, TPA is shown to activate choline-phosphate cytidylyltransferase (EC 2.7.7.15), the regulatory enzyme of the CDP-choline pathway, by stimulating redistribution of the inactive cytosolic form of the enzyme to the membrane. Redistribution was quantitative. TPA reduced cytosolic activity from 3.5 ± 0.4 to 1.5 ± 0.3 nmol·min-1·107 cells-1 and enhanced particulate activity from 2.5 ± 0.4 to 4.9 ± 0.6 nmol·min-1·107 cells-1. TRH also stimulated time- and concentration-dependent 32P(i) and [3H]choline incorporation into phosphatidylcholine. An increase was detectable after 5 min; and after 30 min, the levels were 164 ± 9 and 150 ± 11% of control, respectively; EC50 ~ 2 x 10-10 M TRH. These events correlated directly with TRH-induced 32P(i) incorporation into phosphatidylcholine. TRH also stimulated redistribution of cytidylyltransferase specific activity. TRH reduced cytosolic activity 45% and enhanced particulate activity 51%. Neither TRH nor TPA stimulated phosphatidylcholine degradation. In cells down-modulated for protein kinase C (Ca2+/phospholipid-dependent protein kinase), the effects of TPA and TRH on 32P(i) incorporation into phosphatidylcholine were abolished. However, TRH-induced incorporation into phosphatidylinositol still occurred. These studies provide evidence that hormones may regulate phosphatidylcholine metabolism via the protein kinase C pathway.
Keywords: nonhuman; animal cell; cell line; in vitro study; dose-response relationship, drug; kinetics; choline; protein kinase c; radioisotope; phosphates; phosphatidylcholine; phorbol ester; tetradecanoylphorbol acetate; endocrine system; intoxication; hypophysis; pituitary gland; phosphatidylcholines; support, u.s. gov't, p.h.s.; protirelin
Journal Title: Journal of Biological Chemistry
Volume: 262
Issue: 30
ISSN: 0021-9258
Publisher: American Society for Biochemistry and Molecular Biology  
Date Published: 1987-10-25
Start Page: 14525
End Page: 14530
Language: English
PUBMED: 3117787
PROVIDER: scopus
DOI: 10.1016/S0021-9258(18)47827-1
DOI/URL:
Notes: Article -- Export Date: 5 February 2021 -- Source: Scopus
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  1. Richard N Kolesnick
    299 Kolesnick