title: A role for endocannabinoids in acute stress-induced suppression of the hypothalamic-pituitary-gonadal axis in male rats.
abstract: OBJECTIVE
  Stress is known to be an inhibitor of the reproductive hypothalamic-pituitary-gonadal (HPG) axis. However, the neural and molecular connections between stress and reproduction are not yet understood. It is well established that in both humans and rodents, kisspeptin (encoded by the kiss1 gene) is a strong stimulator of the HPG axis. In the present study we hypothesized that endocannabinoids, an important neuromodulatory system in the brain, can act on the HPG axis at the level of kiss1 expression to inhibit reproductive function under stress.
  
  
  METHODS
  Adult male Wistar rats were unilaterally implanted with an intracerebroventricular cannula. Afterwards, the animals were exposed to immobilization stress, with or without the presence of the cannabinoid CB1 receptor antagonist AM251 (1 µg/rat). Blood samples were collected through a retro-orbital plexus puncture before and after stress. Five hours after the stress, brain tissue was collected for reverse transcriptase-quantitative polymerase chain reaction measurements of kiss1 mRNA.
  
  
  RESULTS
  Immobilization stress (1 hour) resulted in a decrease in the serum luteinizing hormone concentration. Additionally, kiss1 gene expression was decreased in key hypothalamic nuclei that regulate gonadotrophin secretion, the medial preoptic area (mPOA), and to some extent the arcuate nucleus (ARC). A single central administration of AM251 was effective in blocking these inhibitory responses.
  
  
  CONCLUSIONS
  These findings suggest that endocannabinoids mediate, at least in part, immobilization stress-induced inhibition of the reproductive system. Our data suggest that the connection between immobilization stress and the HPG axis is kiss1 expression in the mPOA rather than the ARC.
authors: Department of Physiology, School of Medicine, Tehran University of Medical Science, Tehran, Iran.
authors: Maryam
authors: M
authors: Karamikheirabad
authors: Department of Physiology, Medical School, Shahid Beheshti Medical Sciences University, Tehran, Iran.
authors: Gila
authors: G
authors: Behzadi
authors: Department of Physiology, School of Medicine, Tehran University of Medical Science, Tehran, Iran.
authors: Mahdieh
authors: M
authors: Faghihi
authors: Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran.
authors: Reza
authors: R
authors: Raoofian
authors: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors: Shahram
authors: S
authors: Ejtemaei Mehr
authors: Centre for Neuroendocrinology and Department of Anatomy, University of Otago School of Medical Sciences, Dunedin, New Zealand.
authors: Wieteke Ameliek
authors: WA
authors: Zuure
authors: Department of Physiology, School of Medicine, Tehran University of Medical Science, Tehran, Iran.
authors: Hamid Reza
authors: HR
authors: Sadeghipour
keywords: Cannabinoids; Immobilization; Kisspeptins; Rats; Reproduction