Clues to understanding the oxidation of estradiol in humans: effects of acute infectious hepatitis, autoimmune hepatitis, and chronic liver disease.
Determination of 2- and 16alpha-hydroxylation of estradiol in patients with a variety of liver disorders using a dynamic method of quantitating the extent of hydroxylation revealed specific and characteristic differences in the metabolic response. Patients with acute or silent variants of hepatitis B had estrogen metabolite patterns that were indistinguishable from those found in the control subjects. Female patients with autoimmune hepatitis (formerly known as lupoid hepatitis), however, showed a moderate significant decrease (P < 0.01) in 2-hydroxylation as compared with normal controls (mean 16.3 +/- 1.9 vs. 33.9 +/- 2.5), with no significant change in 16alpha-hydroxylation. Male and female subjects with chronic alcoholic cirrhosis were almost devoid of 2-hydroxylation (mean 2.9 +/- 0.5, P < 0.01), but did show a significant increase in 16alpha-hydroxylation (P < 0.01). The results, therefore, show that the alterations in patterns of biological oxidation are highly specific and do not reflect a general inability to metabolize estrogens in the cirrhotic patient. However, the results also suggest the possibility that a substantial fraction of 16alpha-hydroxylation may occur elsewhere in the body at sites other than in the liver, explaining why this biotransformation pathway is elevated, while the reaction at C-2 is almost absent in the alcoholic cirrhotic subjects.
Lahita
Robert G
RG
Beth Israel Medical Center, Newark, New Jersey 07112, USA. rlahita@att.net
Schaefer
Robert A
RA
Bradlow
H Leon
HL
Kreek
Mary Jeanne
MJ
D000208:Acute Disease; D000328:Adult; D002908:Chronic Disease; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D006509:Hepatitis B / Q000378:metabolism*; D019693:Hepatitis, Autoimmune / Q000378:metabolism*; D006801:Humans; D006900:Hydroxylation; D008107:Liver Diseases / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction
D004958:Estradiol