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.