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Title: Estrogenic compounds inhibit gap junctional intercellular communication in mouse Leydig TM3 cells

Abstract

Some estrogenic compounds are reported to cause testicular disorders in humans and/or experimental animals by direct action on Leydig cells. In carcinogenesis and normal development, gap junctional intercellular communication (GJIC) plays an essential role in maintaining homeostasis. In this study, we examine the effects of diethylstilbestrol (DES, a synthetic estrogen), 17{beta}-estradiol (E{sub 2}, a natural estrogen), and genistein (GEN, a phytoestrogen) on GJIC between mouse Leydig TM3 cells using Lucifer yellow microinjection. The three compounds tested produced GJIC inhibition in the TM3 cells after 24 h. Gradually, 10 {mu}M DES began to inhibit GJIC for 24 h and this effect was observed until 72 h. On the other hand, both 20 {mu}M E{sub 2} and 25 {mu}M GEN rapidly inhibited GJIC in 6 h and 2 h, respectively. The effects continued until 24 h, but weakened by 72 h. Furthermore, a combined effect at {mu}M level between DES and E{sub 2} on GJIC inhibition was observed, but not between GEN and E{sub 2}. DES and E{sub 2} showed GJIC inhibition at low dose levels (nearly physiological estrogen levels) after 72 h, but GEN did not. DES-induced GJIC inhibition at 10 pM and 10 {mu}M was completely counteracted by ICI 182,780more » (ICl), an estrogen receptor antagonist. On the other hand, the inhibitory effects on GJIC with E{sub 2} (10 pM and 20 {mu}M) and GEN (25 {mu}M) were partially blocked by ICI or calphostin C, a protein kinase C (PKC) inhibitor, and were completely blocked by the combination of ICI and calphostin C. These results demonstrate that DES inhibits GJIC between Leydig cells via the estrogen receptor (ER), and that E{sub 2} and GEN inhibit GJIC via ER and PKC. These estrogenic compounds may have different individual nongenotoxic mechanism including PKC pathway on testicular carcinogenesis or development.« less

Authors:
 [1];  [2];  [3]
  1. Department of Bioenvironmental Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670 (Japan) and Toxicology Laboratory, Pharmaceuticals Research Unit, Research and Development Division, Mitsubishi Pharma Corporation, Kisarazu 292-0818 (Japan) and Environmental Health Science Project for Future Generations, Graduate School of Medicine, Chiba University, Chiba 260-8670 (Japan). E-mail: Iwase.Yumiko@mg.m-pharma.co.jp
  2. Department of Bioenvironmental Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670 (Japan) and Environmental Health Science Project for Future Generations, Graduate School of Medicine, Chiba University, Chiba 260-8670 (Japan). E-mail: fukata@faculty.chiba-u.jp
  3. Department of Bioenvironmental Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670 (Japan) and Environmental Health Science Project for Future Generations, Graduate School of Medicine, Chiba University, Chiba 260-8670 (Japan) and Center for Environment, Health and Field Sciences, Chiba University, Kashiwa 277-0882 (Japan). E-mail: cmori@faculty.chiba-u.jp
Publication Date:
OSTI Identifier:
20783470
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 212; Journal Issue: 3; Other Information: DOI: 10.1016/j.taap.2005.08.005; PII: S0041-008X(05)00510-7; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CARCINOGENESIS; ESTRADIOL; HOMEOSTASIS; INHIBITION; MICE; RECEPTORS; TESTES

Citation Formats

Iwase, Yumiko, Fukata, Hideki, and Mori, Chisato. Estrogenic compounds inhibit gap junctional intercellular communication in mouse Leydig TM3 cells. United States: N. p., 2006. Web. doi:10.1016/j.taap.2005.08.005.
Iwase, Yumiko, Fukata, Hideki, & Mori, Chisato. Estrogenic compounds inhibit gap junctional intercellular communication in mouse Leydig TM3 cells. United States. doi:10.1016/j.taap.2005.08.005.
Iwase, Yumiko, Fukata, Hideki, and Mori, Chisato. Mon . "Estrogenic compounds inhibit gap junctional intercellular communication in mouse Leydig TM3 cells". United States. doi:10.1016/j.taap.2005.08.005.
@article{osti_20783470,
title = {Estrogenic compounds inhibit gap junctional intercellular communication in mouse Leydig TM3 cells},
author = {Iwase, Yumiko and Fukata, Hideki and Mori, Chisato},
abstractNote = {Some estrogenic compounds are reported to cause testicular disorders in humans and/or experimental animals by direct action on Leydig cells. In carcinogenesis and normal development, gap junctional intercellular communication (GJIC) plays an essential role in maintaining homeostasis. In this study, we examine the effects of diethylstilbestrol (DES, a synthetic estrogen), 17{beta}-estradiol (E{sub 2}, a natural estrogen), and genistein (GEN, a phytoestrogen) on GJIC between mouse Leydig TM3 cells using Lucifer yellow microinjection. The three compounds tested produced GJIC inhibition in the TM3 cells after 24 h. Gradually, 10 {mu}M DES began to inhibit GJIC for 24 h and this effect was observed until 72 h. On the other hand, both 20 {mu}M E{sub 2} and 25 {mu}M GEN rapidly inhibited GJIC in 6 h and 2 h, respectively. The effects continued until 24 h, but weakened by 72 h. Furthermore, a combined effect at {mu}M level between DES and E{sub 2} on GJIC inhibition was observed, but not between GEN and E{sub 2}. DES and E{sub 2} showed GJIC inhibition at low dose levels (nearly physiological estrogen levels) after 72 h, but GEN did not. DES-induced GJIC inhibition at 10 pM and 10 {mu}M was completely counteracted by ICI 182,780 (ICl), an estrogen receptor antagonist. On the other hand, the inhibitory effects on GJIC with E{sub 2} (10 pM and 20 {mu}M) and GEN (25 {mu}M) were partially blocked by ICI or calphostin C, a protein kinase C (PKC) inhibitor, and were completely blocked by the combination of ICI and calphostin C. These results demonstrate that DES inhibits GJIC between Leydig cells via the estrogen receptor (ER), and that E{sub 2} and GEN inhibit GJIC via ER and PKC. These estrogenic compounds may have different individual nongenotoxic mechanism including PKC pathway on testicular carcinogenesis or development.},
doi = {10.1016/j.taap.2005.08.005},
journal = {Toxicology and Applied Pharmacology},
number = 3,
volume = 212,
place = {United States},
year = {Mon May 01 00:00:00 EDT 2006},
month = {Mon May 01 00:00:00 EDT 2006}
}