The Metabolism of Estrogens by the Human Liver Studied in Vitro12

Abstract

In the preceding paper (1) a method was described which permits the simple calorimetric estimation of microgram amounts of estrogens in the presence of tissues. The results obtained by the use of this method in a study of the in vitro metabolic action of rat liver on 17-p8 estradiol were also reported.In the present paper we are reporting a similar study on human liver. The original motive for this study was to evaluate whether a deficiency of the metabolic function of the liver exists in patients with cancer of the uterus. Patients with this type of cancer and other diseases were studied. METHODSThe procedures described in the preceding paper for the incubation of liver slices, the extraction of the estrogens and the calorimetric method for the measurement of estrogens were used in the present work and found to be applicable without modification to the study of human liver.Human liver specimens were obtained at laparotomy from patients with various surgical diseases. The patients were unselected. The liver specimen was immersed into ice-cold Krebs solution in the operating room, immediately transferred to the laboratory and the incubation experiment begun. The time interval between surgical removal of the specimen and the beginning of the incubation period did not exceed 10 minutes and was comparable to the time interval obtaining in the experiments with rat liver.The liver specimen consisted of a wedge of tissue resected from the anterior border and weighing approximately 2 gms. Sufficient tissue was available in each case to run the metabolic, the control and the blank experiments with slices from the same bloc of tissue.

Alpha2-macroglobulin levels in disease in man

“…Fourteen of the 25 liver disease patients were on ACTH or corticosteroid therapy but this was not related to %e-macroglobulin concentration either in this group or in the patients with rheumatoid arthritis. If, however, cx2-macroglobin is involved in oestrogen metabolism, as the higher levels in normal women and especially in pregnant women suggest, then the marked increase in menwith chronic liver disease could reflect failure of oestrogen inactivation (Tagnon, Lieberman, Schulman, and Brunschwig, 1952). There is clinical evidence of Alpha2-macroglobulin levels in disease in man oestrogen excess in male, but not female, cirrhotics (Sherlock, 1963).…”

Artificial Estrogens

“…The average human liver was found to be capable of metabolizing 11.5 g. of "«''-estradiol in 25 hr. (484), but there is no proved relationship for in vivo inactivating ability. Apparently the ability of liver to inactivate an estrogen depends on the animal; human (514) and monkey (184) liver is inferior to rat liver.…”

The Effect of Estrogen on Water and Electrolyte Metabolism. Ii. Hepatic Disease

“…Although somewhat more controversial (17), the balance of evidence indicates that in humans also estrogens are chiefly inactivated in the liver (18,19).…”