Epoxide hydrolase affects estrogen production in the human ovary.
To investigate the mechanisms of ovarian cell differentiation, we raised a new monoclonal antibody, HCL-3, which reacted with human luteal cells. It also reacted with human and porcine hepatocytes. The immunoaffinity-purified HCL-3 antigen from human corpora lutea (CL) was shown to be a 46-kDa protein. The N-terminal 22 amino acids of the 46-kDa protein from porcine liver exhibited high homology (82%) to human microsomal epoxide hydrolase (mEH). The purified HCL-3 antigen from human CL or porcine liver showed EH enzyme activity, confirming that HCL-3 antigen is identical to mEH, which is reported to detoxify the toxic substrates in the liver. In human follicles, mEH was immunohistochemically detected on granulosa and theca interna cells. In the menstrual and pregnant CL, mEH was also expressed on large and small luteal cells. A competitive inhibitor of EH, 1,2-epoxy-3,3,3-trichloropropane, inhibited the conversion of estradiol from testosterone by granulosa cells cultured in vitro, indicating the involvement of mEH in ovarian estrogen production. Because anticonvulsant sodium valproate and its analogues were reported to inhibit EH enzyme activity, these findings provide a new insight into the etiology of endocrine disorders that are frequently observed among epileptic patients taking anticonvulsant drugs.
Hattori
N
N
Department of Gynecology and Obstetrics, Faculty of Medicine, Kyoto University, Japan.
Fujiwara
H
H
Maeda
M
M
Fujii
S
S
Ueda
M
M
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000927:Anticonvulsants / Q000009:adverse effects; D001141:Aromatase / Q000378:metabolism; D004700:Endocrine System Diseases / Q000139:chemically induced; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors / Q000502:physiology*; D004967:Estrogens / Q000096:biosynthesis*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008861:Microsomes / Q000201:enzymology; D008875:Middle Aged; D008969:Molecular Sequence Data; D010053:Ovary / Q000378:metabolism* / Q000502:physiology; D011247:Pregnancy; D013552:Swine
D000911:Antibodies, Monoclonal; D000927:Anticonvulsants; D004791:Enzyme Inhibitors; D004967:Estrogens; D001141:Aromatase; D004851:Epoxide Hydrolases