Can endocrine factors influence pathogenetic mechanisms in chronic active hepatitis (CAH) and primary biliary cirrhosis (PBC)? A hypothesis

Abstract

CAH and PBC are more common in females than in males. The age distribution and some symptoms indicate a poor or declining function of the corpus luteum. Many estrogens induce hepatic functional disturbances and may bind covalently to hepatic proteins. Bile acid formation and steroid hydroxylation are genetically controlled; many enzymes involved are stimulated by progesterone and possibly by glucocorticoids. A pathological bile might damage periportal hepatocytes in CAH and bile ducts in PBC. Toxic and/or immunological mechanisms might be involved. Disturbed secretion or effects of female sex steroids, glucocorticoids, adrenal or ovarian androgens, thyroid hormones, growth hormone and prolactin and pineal melatonin at the hepatic level and/or by altering the patient's general mode of immunological response, may influence the course of CAH and PBC. The sex distribution and familial crowding of these diseases might be due to genetically controlled endocrine and metabolic disturbances possibly responsive to therapeutic interventions other than those commonly used at present.