Parathyroid hormone and uterine contraction
Shew, Ronald Lewis
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The purpose of the present investigation was to examine the effect of synthetic bovine parathyroid hormone [bPTH-(l-34)] on the contraction of rat uterine horns iii vitro. The studies were designed: 1) to examine the effect of bPTH-(.l-34) on uterine contraction stimulated by various contractile agonists as well as by electrical stimulation, 2) to determine whether the uterine response to bPTH-(l-34) treatment was specific or merely due to the addition of polypeptide molecules to the in vitro tissue bath, 3) to investigate the effect of oxidation of bPTH-(l-34) molecule on the observed uterine response to the hormone, 4) to determine if the action of bPTH-(,l-34) on stimulated uterine contraction was direct or indirect and 5) to examine the possible mechanism by which bPTH-(.l-34) alters uterine contraction. Synthetic bPTH- (1-34) significantly diminished the magnitude of uterine contraction initiated by oxytocin, prostaglandin F-a (PGF a), acetylcholine (Ach) or electrical stimulation. In contrast, bovine serxim albumin (BSA), corticotropin inhibiting peptide (CIP) and salmon calcitonin (sCT) did not reduce oxytocin stimulated uterine contraction. Synthetic bPTH-(1-34) obtained from two different sources both diminished the magnitude of uterine contraction stimulated by oxytocin. Oxidation of bPTH-(1-34) by hydrogen peroxide destroyed the ability of the hormone to diminish oxytocin stimulated uterine contraction. However the effect of bPTH-(.l-34) was not blocked or reversed by anticholinergic (atropine), antiadrenergic (a-phentolamine, g-propranolol), or antihistaminergic (H1-pyrilamine, H2-cimetidine) drugs. Similarly, indomethacin, a prostaglandin synthetase inhibitor, also did not inhibit the hormone's effect. The effect of bPTH-(l-34) was enhanced by theophylline and 1-methyl-3-i3obutylxanthine (MIX) and was partially destroyed with imidazole. In addition, N 0 -dibutyryl-adenosine-3', 5'-cyclic phosphate also reduced oxytocin stimulated contraction. Finally, bPTH-(l-34) was shown to increase the levels of radioimmunoassable cyclic-3', 5'-adenosine monophosphate (cAI'lP) in uterine tissue. These results suggest that: 1) bPTH-(l-34) is capable of reducing uterine contraction stimulated by a variety of contractile agonists, 2) the effect of bPTH-(1-34) on uterine contraction was not caused by a contaminant in the hormone preparation nor due to a general action of polypeptides on uterine contraction in vitro, 3) alteration of the structural configuration of bPTH-(l-34) by H_0_ oxidation effectively abolishes the effect on uterine contraction, 4) the bPTH-(.l-34) effect is due to the direct action of the hormone on uterine tissue, and 5) the effect of bPTH- (1-34) may be mediated by cyclic-AMP.