Direct effect of thyroxine on pig sphincter of Oddi contractility

Sphincter of Oddi (SO) motility has an important role in the regulation of bile flow. SO function disturbances (stenosis or dyskinesia) may prevent no rmal bile flow and thus enhance the probability of common bile duct (CBD) s tone formation. Previously we have shown that there is an increased prevale nce of diagnosed hypothyroidism in CBD stone patients, compared with gallbl adder stone patients or age-, sex-, and hospital-admission-adjusted control s. The present study was done to test the hypothesis that thyroxine directl y effects the SO. The specificity of the effects of thyroxine were studied by comparing with triiodothyronine (T-3), progesterone, cortisone, estrogen , and testosterone. For ex vivo studies three or four successive 1 to 1.5-m m SO rings were prepared from each pig and placed between two hooks in oxyg enated physiologic salt solution at 37 degreesC. SO contraction was measure d with isometric force displacement transducers and registered on a polygra ph. Each SO ring was stimulated with KCl (125 mM), acetylcholine (ACh; 10 o r 100 muM) and histamine (Hist; 10 or 100 muM) with and without thyroxine ( 10(-10) or 10(-8) M), T-3 (10(-9) or 10(-7) M), progesterone (1 muM), corti sone (1 muM), estrogen (1 muM), or testosterone (1 nM) in the medium. KCl, ACh, and Hist induced strong contractions in the SO rings. The addition of thyroxine did not influence significantly the KCl-induced contractions, but the ACh- and Hist-induced contractions decreased by a mean of 37-44% (P < 0.001) and 54-56% (P < 0.001), respectively, as compared to the contraction s without thyroxine. Triiodothyronine had a similar inhibitory effect to th yroxine, whereas cortisone, estrogen, and testosterone had no effect. Proge sterone decreased the KCl-, ACh-, and Hist-induced SO contractions. In conc lusion, physiological concentrations of thyroxine have an inhibitory effect on receptor-mediated ACh and Hist, but not on the nonspecific KCl-induced SO contraction ex vivo. The inhibitory effect is similar in thyroxine and t riiodothyronine. Of the steroid hormones, only progesterone nonspecifically ameliorates SO contractions ex vivo. Because the effect of thyroxine on th e SO is prorelaxing, the lack of thyroxine may result in an increased tensi on of the SO.