Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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Effects of Propyl Pyrazole Triol on the Blood Vessel-Dilation and Cellular Morphology of Liver and Kidney in Adult Male Mouse

성체 수컷 생쥐에서 간장과 신장의 혈관 확장 및 세포 형태에 미치는 Propyl Pyrazole Triol의 영향

  • Lee, Eun-Jung (Department of Biology, College of Natural Sciences, Sunchon National University) ;
  • Lee, Yu-Mi (Department of Biology, College of Natural Sciences, Sunchon National University) ;
  • Choe, Eun-Sang (Department of Biology, College of Natural Sciences, Pusan National University) ;
  • Seong, Chi-Nam (Department of Biology, College of Natural Sciences, Sunchon National University) ;
  • Cho, Hyun-Wook (Department of Biology, College of Natural Sciences, Sunchon National University)
  • 이은정 (순천대학교 자연과학대학 생명과학) ;
  • 이유미 (순천대학교 자연과학대학 생명과학) ;
  • 최은상 (부산대학교 자연과학대학 생명과학부) ;
  • 성치남 (순천대학교 자연과학대학 생명과학) ;
  • 조현욱 (순천대학교 자연과학대학 생명과학)
  • Published : 2006.12.30
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Abstract

The present study was designed to characterize the effects of estrogen receptor agonist (4,4',4'-(4-Propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol, PPT) on liver and kidney in male mouse using a light microscopic analysis. PPT was subcutaneously given to adult male mice at a weekly dosage of 178.6mg/kg in a volume 0.08 ml of vehicle for 3, 5 and 8 weeks. There were differences in body and organ weights between control and the treated groups. Body and kidney weights were decreased in treated group whereas, liver weight was increased. In microscopic observations, sinusoidal diameter in liver of treated group was increased 156%, 216% and 255% on week 3, 5 and 8 respectively. Compared to the control, diameter of proximal convoluted tubules in kidney was increased 37% and 43% or week 5 and 8 in treated group. Whereas, height of epithelial cells in the proximal tubules was reduced at all time points. These results suggest that microstructure of liver and kidney was changed by treatment of estrogen receptor agonist PPT in the male mice.

Keywords

References

  1. Brunette, M.G. and Leclerc, M. (2001): Effects of estrogen on calcium and sodium transport by the nephron luminal membranes. J. Endocrinol., 170, 441-450 https://doi.org/10.1677/joe.0.1700441
  2. Cappon, G.D., Horimoto, M. and Hurtt, M.E. (2004): Reproductive toxicity assessment of lasofoxifene, a selective estrogen receptor modulator (SERM), in male rats. Birth Defects Res., (Part B) 71, 142-149 https://doi.org/10.1002/bdrb.20008
  3. Cho, H.W., Nie, R., Carnes, K., Zhou, Q., Sharief, N.A.Q. and Hess, R.A. (2003): The antiestrogen ICI 182,780 induces early effects on the adult male mouse reproductive tract and long-term decreased fertility without testicular atrophy. Reprod. Biol. Endocrinol., 1, 57 https://doi.org/10.1186/1477-7827-1-57
  4. Cignarella, A., Paoletti, R. and Puglisi, L. (2001): Direct Effects of estrogen on the vessel wall. Med. Res. Rev., 21, 171-184 https://doi.org/10.1002/1098-1128(200103)21:2<171::AID-MED1005>3.0.CO;2-4
  5. Cohen, I.R., Sims, M.L., Robbins, M.R., Lakshmanan, M.C., Francis, P.C. and Long, G.G. (2000): The reversible effects of raloxifene on luteinizing hormone levels and ovarian morphology in mice. Reprod. Toxicol., 14, 37-44 https://doi.org/10.1016/S0890-6238(99)00065-9
  6. Cook, J.C., Johnson, L., O'Connor, J.C., Biegel, L.B., Krams, C.H., Frame, S.R. and Hurtt, M.E. (1998): Effects of dietary 17 beta-estradiol exposure on serum hormone concentrations and testicular parameters in male Crl:CD BR rats. Toxicol. Sci., 44, 155-168
  7. Couse, J.F. and Korach, K.S. (1999): Estrogen receptor null mice: What have we learned and where will they lead us? Endocrine Rev., 20, 358-417 https://doi.org/10.1210/er.20.3.358
  8. Edwards, R., Colombo, T. and Greaves, P. (2002): Have you seen this? peliosis hepatis. Toxicol. Pathol., 30, 521-523 https://doi.org/10.1080/01926230290105686
  9. Farhat, M.Y., Lavigne, M.C. and Ramwell, P.W. (1996): The vascular protective effects of estrogen. FASEB J., 10, 615-624 https://doi.org/10.1096/fasebj.10.5.8621060
  10. Frasor, J., Barnett, D.H., Danes, J.M., Hess, R., Parlow, A.F. and Katzenellenbogen, B.S. (2003): Response-specific and ligand dose-dependent modulation of estrogen receptor (ER) $\alpha$ activity by ER$\beta$ in the uterus. Endocrinol., 144, 3159-3166 https://doi.org/10.1210/en.2002-0143
  11. Grese, T.A. and Dodge, J.A. (1998): Selective estrogen receptor modulators (SERMs). Curr. Pharm. Des., 4, 71-92
  12. Han, H.J., Jung, J.C. and Taub, M. (1999): Response of primary rabbit kidney proximal tubule cells to estrogens. J. Cell. Physiol., 178, 35-43 https://doi.org/10.1002/(SICI)1097-4652(199901)178:1<35::AID-JCP5>3.0.CO;2-P
  13. Hess, R.A. (2003): Estrogen in the adult male reproductive tract: a review. Reprod. Biol. Endocrinol., 1, 52 https://doi.org/10.1186/1477-7827-1-52
  14. Hess, R.A., Bunick, D., Lee, K.H., Bahr, J., Korach, K.S. and Lubahn, D.B. (1997): A role for oestrogens in the male reproductive system. Nature, 390, 509-512 https://doi.org/10.1038/37352
  15. Kraichely, D.M., Sun, J., Katzenellenbogen, J.A. and Katzenellenbogen, B.S. (2000): Conformational changes and coactivator recruitment by novel ligands for estrogen receptor-$\alpha$ and estrogen receptor-$\beta$: Correlations with biological character and distinct differences among SRC coactivator family members. Endocrinol., 141, 3534-3545 https://doi.org/10.1210/en.141.10.3534
  16. Kuiper, G.G.J.M., Enmark, E., Pelto-Huikko, M., Nilsson, S. and Gustafsson, J. (1996): Cloning of a novel estrogen receptor expressed in rat prostate and ovary. Proc. Natl. Acad. Sci. USA, 93, 5925-5930
  17. Ma, H., Sprecher, H.W. and Kolattukudy, P.E. (1998): Estrogen-induced production of a peroxisome proliferator-activated receptor (PPAR) ligand in a PPAR$\gamma$-expressing tissue. J. Biol. Chem., 273, 30131-30138 https://doi.org/10.1074/jbc.273.46.30131
  18. Maric, C., Sandberg, K. and Hinojosa-Laborde, C. (2004): Glomerulosclerosis and tubulointerstitial fibrosis are attenuated with 17$\beta$-estradiol in the aging Dahl salt sensitive rat. J. Am. Soc. Nephrol., 15, 1546-1556 https://doi.org/10.1097/01.ASN.0000128219.65330.EA
  19. Oliveira, C.A., Carnes, K., Franca, L.R. and Hess, R.A. (2001): Infertility and testicular atrophy in the antiestrogentreated adult male rat. Biol. Reprod., 65, 913-920 https://doi.org/10.1095/biolreprod65.3.913
  20. Oliveira, C.A., Nie, R., Carnes, K., Franca, L.R., Prins, G.S., Saunders, P.T.K. and Hess, R.A. (2003): The antiestrogen ICI 182,780 decreases the expression of estrogen receptor-alpha but has no effect on estrogen receptorbeta and androgen receptor in rat efferent ductules. Reprod. Biol. Endocrinol., 1, 75 https://doi.org/10.1186/1477-7827-1-75
  21. Pfaffl, M.W., Lange, I.G. and Meyer, H.H.D. (2003): The gastrointestinal tract as target of steroid hormone action: Quantification of steroid receptor mRNA expression (AR, ER$\alpha$, ER$\beta$ and PR) in 10 bovine gastrointestinal tract compartments by kinetic RT-PCR. J. Steroid Biochem. Mol. Biol., 84, 159-166 https://doi.org/10.1016/S0960-0760(03)00025-6
  22. Radzikowska, E., Maciejewski, R., Janicki, K., Madej, B. and Wojtowicz, Z. (2001): The relationship between estrogen and the development of liver vascular disorders. Ann. Univ. Mariae Curie Sklodowska, 56, 189-193
  23. Roesch, D.M. (2006): Effects of selective estrogen receptor agonists on food intake and body weight gain in rats. Physiol. Behavior, 87, 39-44 https://doi.org/10.1016/j.physbeh.2005.08.035
  24. Sakamoto, M., Ueno, T., Nakamura, T., Hashimoto, O., Sakata, R., Kin, M., Ogata, R., Kawaguchi, T., Torimura, T. and Sata, M. (2001): Estrogen upregulates nitric oxide synthase expression in cultured rat hepatic sinusoidal endothelial cells. J. Hepatol., 34, 858-864 https://doi.org/10.1016/S0168-8278(01)00023-X
  25. Sapino, A., Pietribiasi, F., Bussolati, G. and Marchisio, P. (1986): Estrogen- and tamoxifen-induced rearrangement of cytoskeletal and adhesion structures in breast cancer MCF-7 cells. Cancer Res., 46, 2526-2531
  26. Sato, T., Wang, G., Hardy, M.P., Kurita, T., Cunha, G.R. and Cooke, P.S. (2002): Role of systemic and local IGF-I in the effects of estrogen on growth and epithelial proliferation of mouse uterus. Endocrinol., 143, 2673-2679 https://doi.org/10.1210/en.143.7.2673
  27. Shiau, A.K., Barstad, D., Loria, P.M., Cheng, L., Kushner, P.J., Agard, D.A. and Greene, G.L. (1998): The structural basis of estrogen receptor/coactivator recognition and the antagonism of this interaction by tamoxifen. Cell, 95, 927-937 https://doi.org/10.1016/S0092-8674(00)81717-1
  28. Sibonga, J.D., Lotinun, S., Evans, G.L., Pribluda, V.S., Green, S.J. and Turner, R.T. (2003): Dose-response effects of 2- methoxyestradiol on estrogen target tissues in the ovariectomized rat. Endocrinol., 144, 785-792 https://doi.org/10.1210/en.2002-220632
  29. Stauffer, S.R., Coletta, C.J., Tedesco, R., Nishiguchi, G., Carlson, K., Sun, J., Katzenellenbogen, B.S. and Katzenellenbogen, J.A. (2000): Pyrazole ligands: Structure-affinity/activity relationships and estrogen receptor-$\alpha$ selective agonists. J. Med. Chem., 43, 4934-4947 https://doi.org/10.1021/jm000170m
  30. Taylor, A.H. and Al-Azzawi, F. (2000): Immunolocalisation of oestrogen receptor beta in human tissues. J. Mol. Endocrinol., 24, 145-155 https://doi.org/10.1677/jme.0.0240145
  31. Toft, D. and Gorski, J. (1966): A receptor molecule for estrogens: Isolation from the rat uterus and preliminary characterization. Proc. Natl. Acad. Sci. USA, 55, 1574-1581
  32. Tostes, R.C., Nigro, D., Fortes, Z.B. and Carvalho, M.H.C. (2003): Effects of estrogen on the vascular system. Brazilian J. Med. Bio. Res., 36, 1143-1158 https://doi.org/10.1590/S0100-879X2003000900002
  33. Uno, K., Katagiri, H., Yamada, T., Ishigaki, Y., Ogihara, T., Imai, J., Hasegawa, Y., Gao, J., Kaneko, K., Iwasaki, H., Ishihara, H., Sasano, H., Inukai, K., Mizuguchi, H., Asano, T., Shiota, M., Nakazato, M. and Oka, Y. (2006): Neuronal pathway from the liver modulates energy expenditure and systemic insulin sensitivity. Sci., 312, 1656-1659 https://doi.org/10.1126/science.1126010
  34. Wade, G.N. and Heller, H.W. (1993): Tamoxifen mimics the effect of estradiol on food intake, body weight, and body composition in rats. Am. J. Physiol., 264, R1219-1223
  35. Wade, G.N., Gray, J.M. and Blaustein, J.D. (1993): Effects of estrogens and antiestrogens on eating behavior, metabolism, and energy balance. Oncol., 7, 61-68 https://doi.org/10.1159/000223707
  36. Wakeling, A.E., Newboult, E. and Peters, S.W. (1989): Effects of antiestrogens on the proliferation of MCF-7 human breast cancer cells. J. Mol. Endocrinol., 2, 225-234 https://doi.org/10.1677/jme.0.0020225
  37. Wang, H.H., Afdhal, N.H. and Wang, D.Q. (2004): Estrogen receptor alpha, but not beta, plays a major role in 17betaestradiol- induced murine cholesterol gallstones. Gastroenterol., 127, 239-249 https://doi.org/10.1053/j.gastro.2004.03.059
  38. White, R.E. (2002): Estrogen and vascular function. Vascular Pharmacol., 38, 73-80
  39. Winborn, W.B., Sheridan, P.J. and McGill, H.C.Jr. (1987): Sex steroid receptors in the stomach, liver, pancreas, and gastrointestinal tract of the baboon. Gastroenterol., 92, 23-32 https://doi.org/10.1016/0016-5085(87)90835-3
  40. Xiao, S., Gillespie, D.G., Baylis, C., Jackson, E.K. and Dubey, R.K. (2001): Effects of estradiol and its metabolites on glomerular endothelial nitric oxide synthesis and mesangial cell growth. Hypertension, 37, 645-650 https://doi.org/10.1161/01.HYP.37.2.645
  41. Yokomori, H., Oda, M., Ogi, M., Kamegaya, Y., Tsukada, N. and Ishii, H. (2001): Endothelial nitric oxide synthase and caveolin-1 are co-localized in sinusoidal endothelial fenestrae. Liver, 21, 198-206 https://doi.org/10.1034/j.1600-0676.2001.021003198.x