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Mol. Hum. Reprod. Advance Access published online on April 26, 2004
Molecular Human Reproduction, doi:10.1093/molehr/gah062
© 2004 by Oxford University Press
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Received February 2, 2004
Revised March 18, 2004
Accepted March 25, 2004

Article

Characterization of htAKR, a novel gene product in the aldo-keto reductase family specifically expressed in human testis

Yutaro Azuma 1, Toru Nishinaka 2, So Ushijima 1, Jintetsu Soh 3, Masato Katsuyama 2, Hai-Ping Lu 4, Mitsuhiro Kawata 4, Chihiro Yabe-Nishimura 2*, Tsuneharu Miki 3

1 Departments of Pharmacology and Urology, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan
2 Department of Pharmacology, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan
3 Department of Urology, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan
4 Department of Anatomy, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan

* To whom correspondence should be addressed. E-mail: nchihiro{at}koto.kpu-m.ac.jp.


  Abstract

In human testis, expression of a novel member of the aldo-keto reductase family was identified. Based on its testis-specific expression, we termed this protein human testis aldo-keto reductase (htAKR). In addition to four major isoforms, the existence of multiple alternatively spliced products of htAKR was detected using RT-PCR followed by nested PCR. htAKR was a homologue of mouse liver keto-reductase, AKR1E1, with close similarity in their genomic organizations. htAKR4, the longest isoform, was expressed as a non-fused native form. It exhibited a limited activity toward 9,10-phenanthrenequinone, while no activity toward the steroids or prostaglandins was demonstrated. Using the laser capture microdissection technique and RT-PCR, expression of htAKR was detected in testicular germ cells as well as in interstitial cells. The levels of htAKR mRNA in the tissues obtained from seminoma were much lower than those in normal testes. A significant decline in the htAKR expression was observed when NEC8, a cell line originated from a human testicular germ cell tumour, was exposed to phorbol 12-myristate 13-acetate or 5{alpha}-dihydrotestosterone. These results indicate that the expression of htAKR, down-regulated in the testicular tumour, is possibly controlled by mitogenic and hormonal signals.

Key Words: Keywords: aldo-keto reductase, alternative splicing, mouse vas deferens protein, NEC8, seminoma


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