Characterization of Two Isoforms of Mouse 3(17)α-Hydroxysteroid Dehydrogenases of the Aldo-Keto Reductase Family(Biochemistry/Molecular Biology)

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概要

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• Mouse kidney contains two 3(17)α-hydroxysteroid dehydrogenases (HSDs) that show essentially the same properties except for their isoelectric points. However, the structural differences and physiological roles of the two enzymes remain unknown. In this study, we have isolated cDNAs for the two 3(17)α-HSDs from a total RNA sample of mouse kidney by reverse transcription-PCR. The identity of the cDNAs was confirmed by characterization of the recombinant enzymes that showed the same molecular weights, pI values, pH optima, substrate specificity and inhibitor sensitivity as those of the enzymes from mouse kidney. We also found that the recombinant enzymes reduce precursors of neuroactive progesterone derivatives, 5α-dihydrotestoserone, deoxycorticosterone, dehydroepiandrosterone, dehydroepiandrosterone sulfate and estrone at low K_m values of 0.3-2 μM. The two enzymes belonged to the aldo-keto reductase (AKR) family, and their 323-amino acid sequences differed only by five amino acids. The sequences of the two isoforms are identical to those of proteins that are predicted to be encoded in a gene for AKR1C21 in the database of the mouse genome. However, the mRNAs for the two isoforms were expressed in mouse kidney and other tissues, in which their expression levels were different. The results indicate an important role of 3(17)α-HSD in controlling the concentrations of various steroid hormones in the mouse tissues, and suggest the existence of two genes for the two isoforms of the enzyme.

• 社団法人日本薬学会の論文
• 2004-12-01

著者

• HARA Akira

  Laboratory of Biological Chemistry, Department of Applied Biological Chemistry, Faculty of Agricultu

• Hara A

  Laboratory Of Biochemistry Gifu Pharmaceutical University

• Hara Akira

  First Department Of Internal Medicine. Fukui Medical School

• USAMI Noriyuki

  Laboratory of Biochemistry, Gifu Pharmaceutical University

• Usami Noriyuki

  Laboratory Of Biochemistry Gifu Pharmaceutical University

• Usami Noriyuki

  岐阜薬科大学 生化学

• Usami N

  Department Of Hygienic Chemistry Faculty Of Pharmaceutical Sciences Hokuriku University

• Ishikura S

  Laboratory Of Biochemistry Gifu Pharmaceutical University

• Ishikura Shuhei

  Laboratory Of Biochemistry Gifu Pharmaceutical University

• Ishikura Syuhei

  Hospital For Sick Children

• Usami N

  Laboratory Of Biochemistry Gifu Pharmaceutical University

• El-KABBANI Ossama

  Department of Medicinal Chemistry, Victorian College of Pharmacy, Monash University

• Hara Akira

  岐阜薬科大学 生化学研究室

• Hara A

  Department Of Applied Biological Chemistry Faculty Of Agriculture Meijo University

• Hara Akira

  Shonan Institute Of Technology

• ISHIKURA Syuhei

  Laboratory of Biochemistry, Gifu Pharmaceutical University

• NAKAJIMA Satoko

  Laboratory of Biochemistry, Gifu Pharmaceutical University

• KAMEYAMA Akiko

  Laboratory of Biochemistry, Gifu Pharmaceutical University

• SHIRAISHI Hiroaki

  Laboratory of Biochemistry, Gifu Pharmaceutical University

• CARBONE Vincenzo

  Department of Medicinal Chemistry, Victorian College of Pharmacy, Monash University

• Hirakawa Akiha

  3rd Dept. Of Intern. Med. Kyoto Univ.

• Hara Akira

  Laboratory Of Biochemistry Gifu Pharmaceutical University

• Hara Akira

  Department Of Pathology Gifu University School Of Medicine

• Carbone Vincenzo

  Department Of Medicinal Chemistry Victorian College Of Pharmacy Monash University

• Hirakawa Akina

  3rd Medical Clinic Faculty Of Medicine Kyoto University

• Kameyama Akiko

  Laboratory Of Biochemistry Gifu Pharmaceutical University

• Shiraishi Hiroaki

  Laboratory Of Biochemistry Gifu Pharmaceutical University

• Shiraishi Hiroaki

  Endocrine Disrupters Research Laboratory National Institute For Environmental Studies

• El-kabbani Ossama

  Medicinal Chemistry And Drug Action Monash Inst. Of Pharmaceutical Sciences

• El-kabbani Ossama

  Department Of Medicinal Chemistry Victorian College Of Pharmacy Monash University

• Nakajima Satoko

  Laboratory Of Biochemistry Gifu Pharmaceutical University

• Hara Akira

  Laboratory Of Biochemistry And Nutritional Chemistry:(present Address)faculty Of Agriculture Meijo U

• Ishikura Syuhei

  Laboratory Of Biochemistry Gifu Pharmaceutical University

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