Early Exposure to Anti-androgen Compounds Induces the Delay in the Testis Development in Immature Male Rat

항안드로겐성 물질이 성 성숙 이전 단계의 정소에서 미치는 영향 연구

  • Hong Jin (National Institute of Toxicological Research Endocrine Toxicology Division) ;
  • Han Soon-Young (National Institute of Toxicological Research Endocrine Toxicology Division) ;
  • Moon Hyun-Ju (National Institute of Toxicological Research Endocrine Toxicology Division) ;
  • Kang Tae-Seok (National Institute of Toxicological Research Endocrine Toxicology Division) ;
  • Kang Il-Hyun (National Institute of Toxicological Research Endocrine Toxicology Division) ;
  • Kim Tae-Sung (National Institute of Toxicological Research Endocrine Toxicology Division) ;
  • Kim Seung-Hee (National Institute of Toxicological Research Endocrine Toxicology Division) ;
  • Kwon Ki-Sung (National Institute of Toxicological Research Endocrine Toxicology Division)
  • 홍진 (국립독성연구원 내분비장애물질팀) ;
  • 한순영 (국립독성연구원 내분비장애물질팀) ;
  • 문현주 (국립독성연구원 내분비장애물질팀) ;
  • 강태석 (국립독성연구원 내분비장애물질팀) ;
  • 강일현 (국립독성연구원 내분비장애물질팀) ;
  • 김태성 (국립독성연구원 내분비장애물질팀) ;
  • 김승희 (국립독성연구원 내분비장애물질팀) ;
  • 권기성 (국립독성연구원 내분비장애물질팀)
  • Published : 2006.09.01

Abstract

The experiments investigated whether early exposure to testosterone propionate (TP) during prepuberty alters testis development in Sprague-Dawley male rats. We performed Hershberger assay using the stimulated weanling male rats by OECD protocols, cDNA microarray, and Western blot. TP was subcutaneously injected to uncastrated Sprague-Dawley male rat of 22 days old for 10 consecutive days at doses of 0.4, 0.8, 1.0, 1.2, 1.6 mg/kg per day. At necropsy, the following tissues were removed and weighed: combined testes, epididymides (Epi), Cowper's glands (COW), levator am, and bulbocavernosus muscles (LABC), seminal vesicles, together with coagulating gland (SV) and ventral prostate (VP). We found that TP increased the weights of Epi, VP, SV, COW, and LABC, while testis was decreased in a dose-dependent manner. In cDNA microarray analysis of testis, there were significant reductions in the expression of cytochrome P450 11A (CYP11A), the rate-limiting enzyme of steroidogenesis. Taken together these results, TP exposure before puberty in male rats may produce the delay in testis development by inhibiting the CYP11A gene expression.

Keywords

References

  1. Almiron I and Chemes H. Spermatogenic onset. II. FSH modulates mitotic activity of germ and sertoli cells in immature rats, Int J Androl 1988; 76: 235-46
  2. Ashby J and Lefevre PA. The weanling rat as an assay for endocrine disruption Preliminary finding, Reg. Tox. Pharmacol. 1997; 26: 330-337 https://doi.org/10.1006/rtph.1997.1177
  3. Ashby J and Lefevre PA. The peripubertal male rat assay as an alternative to the Hershberger castrated male rat assay for the detection of antiandrogens, oestrogens and metabolic modulators, J. Appl. Toxicol. 2000; 20: 35-47 https://doi.org/10.1002/(SICI)1099-1263(200001/02)20:1<35::AID-JAT633>3.0.CO;2-8
  4. Dufau ML, Ulisse S, Khanum A, Buczko E, Kitamura M, Fabbri A and Namiki M. LH action in the Leydig cell:modulation by angiotensin II and corticotropin releasing hormone, and regulation of P450(17) alpha mRNA, J steroid Biochem 1989; 205-17
  5. Gancarczyk M, Tworzydlo W, Szlachta A, Sadowska J and Bilinska B. Hormonal regulation of oestrogen formation by Leydig cells in vitro: immunocytochemic approach, Folia Biol (Krakow) 2003; 181-8
  6. Gray Jr LE, Wolf C, Lambright C, Mann P, Price M, Cooper RL and Ostby J. Administration of potentially antiandrogenic pesticides (procymidon, linuron, iprodion chlozolinate, p, p′-DDE, and ketoconazole) and toxic substances (dibutyl- and diethylhexyl phthalate, PCB 169, and ethane dimethane sulphonate) during sexual differentiation produces diverse profiles of reproductive malformations in the male rat, Toxicol. Ind. Health 1999; 15: 94-118 https://doi.org/10.1177/074823379901500109
  7. Gray LE, Ostby J, Ferrell J, Rehnberg G, Linder R, Cooper R, Goldman J, Slott V and Laskey J. A dose-response analysis of methoxychor-induced alterations of reproductive development and unction in rat, Fundam. Appl. Toxicol. 1989; 12: 92-108 https://doi.org/10.1016/0272-0590(89)90065-1
  8. Holtz A, Brennan RG, Battiste D and Terner C. Androgen control of an inhibitory modulator of phosphodiesterase in rat epididymis and prostate, Endocrinology 1981; 1538-44
  9. Hershberger L, Shipley E and Meyer R. Myotrophic activity of 19-nor-testosterone and other steroids determined by modified levator ani muscle method, Proc. Soc. Exp. Biol. Med. 1953; 83: 175-180
  10. Kang IH, Kim HS, Shin JH, Kim TS, Moon HH, Kim IY, Choi KS, Kil KS, Park YI, Dong MS and Han SY. Comparison of anti-androgenic activity of flutamide, vinclozolin, procymidone, linuron, and p, p′ DDE in rodent 10-day Hershberger assay, Toxicology 2004; 146-159
  11. Jing Cheng, Fu Juan-Ling, Zhou Zong-can. The inhibitor effets of manganese on steroidogenesis in rat promary Leydig cells by disrupting steroidogenic acute regulatory (StAR) protein expression. Toxicology 2003; 1-10
  12. van Roijen JH, Ooms MP, Weber RF, Brinkmann AO, Grootegoed JA and Vreeburg JT. Comparison of the response of rat testis and accessory sex organs to treatment with testosterone and synthetic androgen methyltrienolone (R1881), J Androl 1997; 51-61