Clin Exp Reprod Med.
2013 Dec;40(4):155-162. 10.5653/cerm.2013.40.4.155.
A role for endocannabinoids in acute stress-induced suppression of the hypothalamic-pituitary-gonadal axis in male rats
- Affiliations
-
- 1Department of Physiology, School of Medicine, Tehran University of Medical Science, Tehran, Iran. sadeghipour@sina.tums.ac.ir
- 2Department of Physiology, Medical School, Shahid Beheshti Medical Sciences University, Tehran, Iran.
- 3Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran.
- 4Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
- 5Centre for Neuroendocrinology and Department of Anatomy, University of Otago School of Medical Sciences, Dunedin, New Zealand.
- KMID: 2167493
- DOI: http://doi.org/10.5653/cerm.2013.40.4.155
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 microg/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.
CONCLUSION
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.
Keyword
MeSH Terms
-
Adult
Animals
Arcuate Nucleus
Axis, Cervical Vertebra*
Brain
Cannabinoids
Catheters
Endocannabinoids*
Gene Expression
Humans
Immobilization
Kisspeptins
Luteinizing Hormone
Male*
Polymerase Chain Reaction
Preoptic Area
Punctures
Rats*
Rats, Wistar
Receptor, Cannabinoid, CB1
Reproduction
RNA, Messenger
Rodentia
Cannabinoids
Endocannabinoids
Kisspeptins
Luteinizing Hormone
RNA, Messenger
Receptor, Cannabinoid, CB1
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