Gallbladder disease is more prevalent in women than men. Estrogen therapy has been associated with an increased incidence of gallbladder disease in both sexes. Further, increased progesterone levels have been implicated in impairment of gallbladder motility in pregnancy. Because sex hormones often exert their action through specific receptors, we investigated whether human gallbladder contains receptors for estrogen and progesterone. Binding of radiolabeled hormones in cytosol and nuclei prepared from human gallbladder of both sexes is indicative of the presence of receptors for both estrogen and progesterone. The binding is saturable, of high affinity and highly specific for its particular type of hormone but not other steroids. Fractionation of sodium molybdate-stabilized gallbladder cytosol on Sephadex G-100 demonstrates that the labeled hormones are not bound to defined proteins such as sex steroid binding globulin or albumin. These studies indicate that human gallbladder contains both estrogen and progesterone receptors, that the presence of these receptors may explain the sensitivity of gallbladder tissue to these hormones and that certain aspects of gallbladder function may be mediated by the interaction of steroid hormones with these receptors.
The observations of an increased incidence of gallstones and related diseases in women combined with the demonstration that gallbladders from guinea pigs pretreated with progesterone demonstrate decreased motility (1) suggest that gallbladder may be a sex hormone responsive tissue. Additional experiments using gallbladders from pregnant guinea pigs suggest that the decreased motility of the gallbladder noted during pregnancy is a function of a reduction in the magnitude of the contractile response to both cholinergic agents and cholecystokinin (2). In addition to these observations, it has been demonstrated that prolonged progesterone treatment results in cholelithiasis in rabbits (3). In an effort to provide a biochemical basis for these many observations, the present study was designed to identify and characterize the cytosolic and nuclear progesterone and estrogen binding proteins present in human gallbladder tissue. The results are consistent with the presence of classic estrogen and progesterone receptors in such tissue.