Abstract：
:Endometrial cancer is the most common malignancy of the female genital tract. Its incidence correlates with prolonged estrogen stimulation unopposed by progesterone or synthetic progestins. Estrogen and progestin action is regulated at the pre-receptor level, by interconversion of active hormones (estradiol (E2), progesterone (P)) with their inactive counterparts (estrone (E1), 20alpha-hydroxyprogesterone (20alpha-OHP)) in target tissues. Expression of enzymes that control the ratio of E2 and P may thus play role in the disease process. We first confirmed that AKR1C1 (human 20alpha-hydroxysteroid dehydrogenase) in a cellular context inactivates P by forming 20alpha-OHP but does not catalyze the reverse reaction. We next examined the expression of AKR1C1 and AKR1C3 (type 5 17beta-hydroxysteroid dehydrogenase) in 16 paired specimens of endometrial cancer and adjacent normal endometrium. Quantification by isoform specific real-time PCR revealed higher expression of AKR1C1 in nine specimens and higher expression of AKR1C3 in four specimens of endometrial cancer. Importantly, upregulation of both enzymes in the same specimen was observed. Since AKR1C1 inactivates P its elevated expression in diseased endometrium may contribute to diminished protection by P, while elevated expression of AKR1C3 which forms E2 in vivo, may contribute to the enhanced estrogen action. It is suggested that the expression of AKR1C1 and AKR1C3 in endometrial cancer will govern the ratio of P:E2.
journal_name
Mol Cell Endocrinoljournal_title
Molecular and cellular endocrinologyauthors
Rizner TL,Smuc T,Rupreht R,Sinkovec J,Penning TMdoi
10.1016/j.mce.2005.10.009keywords:
subject
Has Abstractpub_date
2006-03-27 00:00:00pages
126-35issue
1-2eissn
0303-7207issn
1872-8057pii
S0303-7207(05)00395-3journal_volume
248pub_type
杂志文章abstract：:Peritubular stem Leydig cells (SLCs) have been identified from rat testicular seminiferous tubules. However, no stem cells for peritubular myoid cells have been reported in the adult testis so far. In the present study, we tested the hypothesis that the peritubular SLCs are multipotent and able to form either Leydig o...
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pub_type： 杂志文章,评审
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journal_title：Molecular and cellular endocrinology
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