The Biphasic Stimulation of Proliferation of Leydig Cells by Estrogen Exposure

Details

• Personal Author:
  Du Mond JW Jr. ; Roy D ; Singh KP
• Description:
  In this study, we have examined the influence of diethylstilbestrol (DES) and 17B-estradiol on the proliferation of TM3 Leydig cells, a normalized mouse cell line. Cells were treated with seven different concentrations (1 pg-1 ug/ml) of DES or 17B-estradiol, and cell growth was measured at 24-, 48-, and 72-h periods. DES treatment resulted in a significant (p<0.05) stimulation of cell proliferation. We observed two independent peaks of cell proliferation, one at 1 pg/ml DES (186.87%) and the other at 100 ng/ml DES (248.23%). Cytotoxicity was noted at all time periods with 1 ug/ml DES treatment. 17B-estradiol treatment resulted in a significant stimulation of cell proliferation (p<0.05) with a trend similar in response to that of DES treatment, as peak proliferation was noted with 1 pg/ml 17B-estradiol (125.27%) and 10 ng/ml 17B-estradiol (138.31%). Based on these data, it appears that DES is more mitogenic in these Leydig cells compared to 17B-estradiol. Furthermore, for the first time, we detected that both DES and 17B-estradiol were able to stimulate proliferation of Leydig cells in a biphasic fashion. Cell cycle kinetic analysis revealed that cell entry into the S-phase was higher in the DES treated cells compared to the controls, and doubling times of DES exposed cells were significantly reduced (p<0.05). Co-administration of tamoxifen at a concentration 1000-fold higher than either DES or 17B-estradiol resulted in complete inhibition of cell proliferation. Analysis of expression of ERa and ERB by RT-PCR in untreated Leydig cells, as well as Leydig cells exposed to 1 pg/ml DES, revealed that the transcripts of ERa and ERB were not detectable even after 40 cycles of amplification. A 100-ng/ml dose of DES induced ERa expression by 20-fold. These data suggest that estrogen exposure-mediated increases in cell proliferation, coupled with the decrease in cell cycle time, may allow greater accumulation of DNA damage to occur in the testicular target cells compared to untreated cells under normal cell cycle control. In addition, an unidentified estrogen receptor may be responsible for the mitogenic activity of estrogens at low levels. [Description provided by NIOSH]
• Subjects:
  Animals Estrogens Occupational Health Safety Urogenital System
• Keywords:
  Animal Studies Author Keywords: Cell Cycle Cell Proliferation Cellular Effects DNA Damage ERa And ERB Estrogen Estrogenic Hormones Leydig Cells Testes
• ISSN:
  1019-6439
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Alabama ; OSHA Region 4
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  18
• Issue:
  3
• NIOSHTIC Number:
  nn:20057618
• Citation:
  Int J Oncol 2001 Mar; 18(3):623-628
• Contact Point Address:
  Dr Deodutta Roy, Department of Environmental Health Sciences, School of Public Health, University of Alabama at Birmingham, 317 Ryals Building, 1665 University Blvd., Birmingham, AL 35294-0022, USA
• Email:
  Royd@uab.edu
• Federal Fiscal Year:
  2001
• Performing Organization:
  Deep South Center for Occupational Health and Safety, University of Alabama at Birmingham, Birmingham, AL
• Peer Reviewed:
  True
• Start Date:
  19980701
• Source Full Name:
  International Journal of Oncology
• End Date:
  20040630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:d9bb73142c57cae337c3de788da815b98db5cb905f3c60639a0688f2b05ad7c88ec75824d4ed170a5d3a19ba96364693cb106cf9e5b714285bde477cf69bc02a
• Download URL:
  https://stacks.cdc.gov/view/cdc/214891/cdc_214891_DS1.pdf
• File Type:
  [PDF - 2.52 MB ]