The Atrazine Metabolite Diaminochlorotriazine Suppresses LH Release from Murine LbetaT2 Cells by Suppressing GnRH-Induced Intracellular Calcium Transients

Details

• Personal Author:
  Dooley GP ; Hanneman WH ; Tjalkens RB
• Description:
  The primary metabolite of the herbicide atrazine (ATRA), diaminochlorotriazine (DACT), has been suggested to cause disruption in the hypothalamic--pituitary--gonadal axis leading to inhibition of luteinizing hormone (LH) release. DACT is a reactive electrophile known to form covalent protein adducts both in vitro and in vivo following ATRA exposure and might therefore target proteins involved in GnRH-induced calcium signaling and subsequent LH release. To test this hypothesis, LbetaT2 pituitary cells were exposed to 300 microM DACT for 24 h and examined by fluorescence microscopy for GnRH-induced changes in intracellular calcium and LH release. LbetaT2 cells exposed to DACT had markedly diminished GnRH-induced intracellular calcium transients and a significant decreased LH release in response to GnRH. DACT appeared to cause a selective decrease in caffeine-sensitive ryanodine receptor-operated calcium stores in LbetaT2 cells, rather than in thapsigargin-sensitive ER calcium stores. This sensitivity correlated with the formation of covalent protein adducts by DACT, as determined by mass spectrometry. ERp57 was identified by mass spectrometry as a target of DACT adduction in the ER that could potentially mediate the effects of DACT on inhibition of GnRH-induced calcium signaling and inhibition of LH release. Intracellular calcium responses to GnRH and release of LH were restored in DACT-treated cells with the addition of a calcium ionophore (A23187). These data suggest that DACT forms adducts on proteins involved in calcium handling within the ER and that dysfunction in this critical signaling system is associated with loss of normal sensitivity to GnRH and subsequent decreased release of LH. [Description provided by NIOSH]
• Subjects:
  Agriculture Herbicides Nervous System Occupational Health Safety Urogenital System
• Keywords:
  Agricultural Chemicals Atrazine Cell Signaling Estrogenic Hormones Hormone Activity Neurological Reactions Neurotoxic Agents Protein Biochemistry Reproductive Effects
• ISSN:
  2045-452X
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  Colorado ; OSHA Region 8
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  180-186
• Volume:
  2
• Issue:
  3
• NIOSHTIC Number:
  nn:20051890
• Citation:
  Toxicol Res 2013 May; 2(3):180-186
• Contact Point Address:
  William H. Hanneman, Center for Environmental Medicine, College of Veterinary Medicine and Biomedical Sciences, 1680 Campus Delivery, 135 Physiology Building, Fort Collins, USA
• Email:
  william.hanneman@colostate.edu
• CAS Registry Number:
  Atrazine (CAS RN 1912-24-9)
• Federal Fiscal Year:
  2013
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  Colorado State University - Ft. Collins
• Peer Reviewed:
  True
• Start Date:
  20030915
• Source Full Name:
  Toxicology Research
• End Date:
  20270914
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:611914b20ce82bfc8ec1993e593069ec9d57938d6015c7ae57cfd37cec1a7609b7b7c569bafa8a011d510551d2e587befcf02e19c5bae43fe79bf05e3609da9c
• Download URL:
  https://stacks.cdc.gov/view/cdc/211571/cdc_211571_DS1.pdf
• File Type:
  [PDF - 257.41 KB ]