Parathyroid hormone-related protein and human myometrial cells: action and regulation.
Parathyroid hormone-related protein (PTH-rP), like parathyroid hormone (PTH), acts on myometrial smooth muscle to cause relaxation, and PTH-rP expression has been demonstrated in the myometrium of pregnant and estrogen-treated nonpregnant rats and in human myometrium, leiomyomata and separated myometrial smooth muscle cells in culture. PTH-rP may facilitate the myometrial quiescence characteristic of the first 95% of normal pregnancy and uterine vasorelaxation. This study was conducted to explore further the function and regulation of expression of PTH-rP in human myometrium. Treatment of myometrial smooth muscle cells with analogs of PTH-rP caused an increase the intracellular levels of cAMP and treatment of myometrial cells with forskolin or dibutyryl cyclic AMP caused an increase in the levels of PTH-rP mRNAs. Tetradecanoyl phorbol acetate (TPA) and okadaic acid caused a striking increase in the levels of PTH-rP mRNAs, much greater than that evoked by forskolin, dibutyryl cAMP, or transforming growth factor-beta (TGF-beta). These findings are supportive of the conclusion that myometrial cells respond to PTH-rP with activation of adenylyl cyclase and that PTH-rP gene expression may be modulated by way of a number of distinct intracellular signaling pathways.
Morimoto
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The Cecil H. and Ida Green Center for Reproductive Biology Sciences and the Department of Obstetrics-Gynecology, The University of Texas Southwestern Medical School, Dallas 75235-9051, USA.
Devora
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Mibe
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Casey
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MacDonald
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D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009215:Myometrium / Q000187:drug effects* / Q000502:physiology; D019319:Okadaic Acid / Q000494:pharmacology; D010281:Parathyroid Hormone / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D044162:Parathyroid Hormone-Related Protein; D011247:Pregnancy; D011506:Proteins / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D006063:Chorionic Gonadotropin; C470121:PTHLH protein, human; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D012333:RNA, Messenger; D005576:Colforsin; D019319:Okadaic Acid; D003994:Bucladesine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D003346:Corticotropin-Releasing Hormone; D013755:Tetradecanoylphorbol Acetate