MOLECULAR ANALYSIS FOR CAGREPEATS OF HUMAN ANDROGEN RECEPTOR GENE INJAPANESE INFETILE MALES

• Project/Area Number: 09671722
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: HYOGO COLLEGE OF MEDICINE
• Principal Investigator: KASUMI Hiroyuki HYOGO COLLEGE OF MEDICINE,DEPARTMENT OF OBSTETRICS AND GYNECOLOGY,ASSISTANT PROFESSOR, 医学部, 助手 (00289068)
• Co-Investigator(Kenkyū-buntansha): KOMORI Shinji HYOGO COLLEGE OF MEDICINE,DEPARTMENT OF OBSTETRICS AND GYNECOLOGY,LECTURER, 医学部, 講師 (60195865)
• Project Period (FY): 1997 – 1998
• Project Status: Completed (Fiscal Year 1998)
• Budget Amount: ¥3,000,000 (Direct Cost: ¥3,000,000); Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000); Fiscal Year 1997: ¥2,500,000 (Direct Cost: ¥2,500,000)
• Keywords: Androgen receptor gene / CAG repeat / oligozoospermia / infertility

Research Abstract

Mammalian spermatogenesis is absolutely dependent upon androgen produced via LH action on Leydig cells. Androgen acts directly on Sertoli cells of seminiferous tubules with no direct action on germ cells. Androgen thus promtes the initiation and maintenance of sperrnatogenesis, although the detailed molecular and cellular mechanisms remain obscure.
As androgen acts on target cells through the androgen receptor (AR), defects of the AR result in complete or partial androgen insensitivity syndrome (AIS ) which is observed as a range of phenotypes from complete sex-reversal (female phenotype ) to infertility (male phenotype). Since the AR gene was isolated, many AR gene abnormalities have been reported in cases of AIS.Most abnormalities in the AR gene have been identified with the DNA-binding and hormone-binding domains. Since it was observed that the elongation of CAG repeats in exon 1 of the AR gene caused pathogenesis of X-linked spinal and bulbar muscular atrophy (Kennedy's disease), the N-terminal domain has also been considered to play an important role in AR function.
We analyzed the CAG repeat length in exon 1 of the androgen receptor gene in 59 idiopathic Japanese infertile males with oligozoospermia. 36 fertile males were also analyzed as a control. The number of CAG repeats in infertile males ranged from 14 to 32 (mean 21.2 4.2), whereas the number of CAG repeats in fertile males ranged from 16 to 31 (mean 21.4 3.5). Among infertile males, 6 possessed a short form of 14 CAG repeats and 2 possessed 15 CAG repeats. On the other hand, fertile males did not possess a short form of 14 or 15 CAG repeats. The incidence of infertile males with 14 and 15 CAG repeats was significantly higher than that of fertile males. The results suggest that the reduction of CAG repeats in exon A of the androgen receptor is closely related to impaired spermatogenesis in Japanese infertile males.

Research Products

• [Publications] Komori, S., Tanaka, H., Sakata, K., Tsuji, Y., Shima, H., Koyama, K.: "Shortage of glutamine (CAG) homopolymeric repeats suppresses the expression of androgen gene in a case with the androgen insensitiviy syndrome." Gynecol. Eendocrinol.Vol.12 No.1. 1-8 (1998)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Komori, S., Kasumi, H,.Kanazawa, R., Sakata, K., Nakata, Y., Kato, H.and Koyama, K.: "CAG repeat length of the androgen receptor in Japanese infertile males with oligozoospermia." Mol.Hum.Reprod.Vol.5 No1. (1999)
  • Description: 「研究成果報告書概要(欧文)」より