title: Hepatic cholesterol metabolism in estrogen-treated men.
abstract: Operative liver biopsies were obtained from two male patients who developed gallstone disease during estrogen treatment of metastatic prostatic carcinoma. The heparin-sensitive binding of 125I-low-density lipoprotein (LDL) to liver homogenates (reflecting the expression of the LDL receptor) was determined, together with the activities of the rate-limiting enzymes in cholesterol synthesis [3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase], bile acid production (cholesterol 7 alpha-hydroxylase), and cholesterol esterification (acyl CoA:cholesterol acyl transferase). The results were related to data available in 18 patients (5 male, 13 female) who underwent cholecystectomy because of gallstone disease. The hepatic 125I-LDL-binding activity was increased threefold compared with five controls, and the activity of HMG-CoA reductase was increased twofold. There was no major difference in the activities of cholesterol 7 alpha-hydroxylase or acyl CoA:cholesterol acyl transferase. The concentration of free and total cholesterol in liver microsomes was approximately 30% lower in the estrogen-treated men than in 11 controls. The results indicate that estrogen at pharmacological doses stimulates hepatic LDL-receptor expression and HMG-CoA reductase activity in men. The increased LDL-receptor expression could in part explain the enhanced plasma clearance of injected 125I-LDL and hence the reduction in plasma LDL cholesterol previously shown to occur in estrogen-treated men.
authors.affiliation: Department of Medicine, Karolinska Institute, Huddinge University Hospital, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Angelin
authors.forename: H
authors.initials: H
authors.lastname: Olivecrona
authors.forename: E
authors.initials: E
authors.lastname: Reihnér
authors.forename: M
authors.initials: M
authors.lastname: Rudling
authors.forename: D
authors.initials: D
authors.lastname: Ståhlberg
authors.forename: M
authors.initials: M
authors.lastname: Eriksson
authors.forename: S
authors.initials: S
authors.lastname: Ewerth
authors.forename: P
authors.initials: P
authors.lastname: Henriksson
authors.forename: K
authors.initials: K
authors.lastname: Einarsson
mesh_terms: D000368:Aged; D001646:Bile / Q000737:chemistry; D002769:Cholelithiasis / Q000139:chemically induced / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000032:analysis; D004967:Estrogens / Q000009:adverse effects*; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000032:analysis; D025782:Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent; D008055:Lipids / Q000032:analysis; D008074:Lipoproteins / Q000097:blood; D008099:Liver / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D011388:Prolactin / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy; D011973:Receptors, LDL / Q000378:metabolism; D002785:Sterol O-Acyltransferase / Q000032:analysis; D013739:Testosterone / Q000097:blood
chemical_list: D004967:Estrogens; D008055:Lipids; D008074:Lipoproteins; D011973:Receptors, LDL; D013739:Testosterone; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D025782:Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent; D002790:Cholesterol 7-alpha-Hydroxylase; D002785:Sterol O-Acyltransferase