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 prote...
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Veröffentlicht in: | Endocrinology (Philadelphia) 2000-09, Vol.141 (9), p.3353-3365 |
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Zusammenfassung: | 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. |
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ISSN: | 0013-7227 1945-7170 |
DOI: | 10.1210/endo.141.9.7682 |