Gonadotropin Regulation of Glutathione Synthesis in the Rat Ovary

Details

• Personal Author:
  Faustman EM ; Kavanagh TJ ; Luderer U ; White CC
• Description:
  Glutathione (GSH), an antioxidant and conjugator of electrophilic toxicants, prevents toxicant-mediated destruction of ovarian follicles and oocytes. Ovarian GSH has previously been shown to change with estrous cycle stage in rats, suggesting that the gonadotropin hormones may regulate ovarian GSH synthesis. The present studies tested the hypotheses that [1] estrous cycle-related changes in ovarian GSH result from cyclic changes in protein and mRNA expression of the rate-limiting enzyme in GSH synthesis, glutamate cysteine ligase (GCL, also called y-glutamylcysteine synthetase), and [2] that these changes result from gonadotropin-mediated regulation of GCL subunit expression. In the first experiment, ovaries were harvested from cycling adult female rats on each stage of the estrous cycle. In the second experiment immature female rats were injected with pregnant mare's serum gonadotropin (PMSG) to stimulate follicular development or with vehicle and killed 8, 24, or 48 h later. In both experiments the ovaries were harvested for [1] total GSH assay, [2] Western analysis for GCL catalytic (GCLc) and regulatory (GCLm) subunit protein levels, or [3] Northern analysis for Gclc and Gclm mRNA levels. Ovarian GSH concentrations and Gclc and Gclm mRNA levels, but not GCL subunit protein levels, varied significantly with estrous cycle stage. PMSG administration significantly increased ovarian GSH concentrations 24 and 48 h later. GCLm protein levels increased significantly at 24h and 48h following PMSG. GCLc protein levels did not increase significantly following PMSG. Gcl subunit mRNA levels were not significantly increased at any time point by the planned ANOVA; however, an increase in Gclc at 48 h was identified by t-testing. These results support the hypothesis that gonadotropins regulate ovarian GSH synthesis by modulating GCL subunit expression. [Description provided by NIOSH]
• Subjects:
  Animals Antioxidants Endocrine System Occupational Health Safety Urogenital System
• Keywords:
  Animal Studies Author Keywords: Glutathione Cell Function Estrous Cycle Follicle-stimulating Hormone Glutamate Cysteine Ligase Glutamates Hormone Activity Hormones Luteinizing Hormone Ovary Proteins Reproductive Effects Ribonucleic Acids RNA Y-Glutamylcysteine Synthetase

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• ISSN:
  0890-6238
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  California ; OSHA Region 10 ; OSHA Region 9 ; Washington
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  495-504
• Volume:
  15
• Issue:
  5
• NIOSHTIC Number:
  nn:20058196
• Citation:
  Reprod Toxicol 2001 Sep-Oct; 15(5):495-504
• Contact Point Address:
  Ulrike Luderer, Center for Occupational and Environmental Health, University of California, Irvine, CA, USA
• Email:
  uluderer@uci.edu
• CAS Registry Number:
  Glutathione (CAS RN 70-18-8)
• Federal Fiscal Year:
  2001
• Performing Organization:
  University of California, School of Public Health, Los Angeles, CA
• Peer Reviewed:
  True
• Start Date:
  19990701
• Source Full Name:
  Reproductive Toxicology
• End Date:
  20040630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:9328aa4f6714278172ae935f923770b5c71211c6c73368d233fd60201ab368ba72e6abc438d278314099f1ab937394c2394b07c8123a006fcb6994cf6b9619cc
• Download URL:
  https://stacks.cdc.gov/view/cdc/221331/cdc_221331_DS1.pdf
• File Type:
  [PDF - 571.55 KB ]