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Sunday, January 1, 2012

Endocannabinoids and Gonadal Hormones

Cannabis sativa has historically been a widely consumed plant known for its psychoactive properties and its reported effects on motivation, metabolism, and sexual functioning. The primary active component of cannabis was identified in the 1960s as Δ9-tetrahydrocannabinol (THC). Conclusive evidence for the site of action of THC and other cannabinoids remained elusive until the discovery of the presence of a cannabinoid receptor. Cannabinoid receptors have since been discovered to be part of a major neuromodulatory system known as the endocannabinoid system.

The endocannabinoid system is widespread throughout the central nervous system (CNS) and peripheral regions and regulates a large array of physiological functions and behaviors. The endocannabinoid system contains two types of G protein-coupled cannabinoid receptors: the CB1 receptor and the CB2 receptor. CB1 receptors are found throughout the central nervous system and some peripheral tissues but are most densely expressed in the neurons of the cerebral cortex, hippocampus, amygdala, hypothalamus, basal ganglia outflow tracts, and cerebellum, whereas CB2 receptors are mostly expressed in peripheral tissues and immune cells.

The same can be said for gonadal hormones, and there are several major lines of evidence suggesting that the two systems interact extensively.

First, components of the endocannabinoid system are present throughout the hypothalamic-pituitary-gonadal (HPG) axis, and perturbations to this system cause changes in the HPG.

Second, changes in theHPGaxis alter the expression and function of proteins of the endocannabinoid system.

Third, the endocannabinoid system is implicated in many behavioral and physiological functions, such as sexual behavior, that are known to be regulated by gonadal hormones.

The current review seeks to summarize the findings relating to interactions between endocannabinoids and gonadal hormones.


Gorzalka BB, Dang SS. Endocannabinoids and Gonadal Hormones: Bidirectional Interactions in Physiology and Behavior. Endocrinology. http://endo.endojournals.org/content/early/2011/12/28/en.2011-1643.abstract

Endocannabinoids act as a major neuromodulatory system in a variety of physiological and behavioral functions. Three major lines of evidence suggest that the endocannabinoid system interacts with gonadal hormones. First, the endocannabinoid system is implicated in behaviors and physiological functions that are known to be regulated in part by gonadal hormones. Second, receptors and metabolic enzymes of the endocannabinoid system are localized extensively on structures in the hypothalamic-pituitary-gonadal axis. Third, changes in levels of gonadal hormones alter endocannabinoid signaling. Here we reviewed and summarized the current evidence regarding the interaction between the endocannabinoid system and androgens, estrogens, and progesterone. Overall, it appears that bidirectional interactions characterize the relationship between endocannabinoids and gonadal hormones, with endocannabinoids down-regulating hypothalamic-pituitary-gonadal activity and gonadal hormones modulating protein expression in the endocannabinoid system. An understanding of these interactions will have implications for elucidating the neuroendocrine mechanisms underlying a number of behavioral and physiological functions as well as potential pharmaceutical treatments for disorders of these functions.


Summary of major interactions of the endocannabinoid system with androgens. Endocannabinoids suppress release of GnRH, LH, and FSH. Red arrows and boxes represent interactions in the primary feedback loop of androgens and the endocannabinoid system. Black arrows and blue boxes represent other interactions occurring beyond the primary feedback loop.


Summary of major interactions of the endocannabinoid system with estrogens. Endocannabinoids suppress release of GnRH, LH, and FSH. Estrogens regulate functioning of FAAH, the principal catabolic enzyme for the endocannabinoid anandamide. Red arrows and boxes represent interactions in the primary feedback loop of androgens and the endocannabinoid system. Black arrows and blue boxes represent other interactions occurring beyond the primary feedback loop.


Summary of major interactions of the endocannabinoid system with progesterone. Endocannabinoids suppress release of GnRH, LH, and FSH. Progesterone regulates functioning of FAAH, the principal catabolic enzyme for the endocannabinoid anandamide. Red arrows and boxes represent interactions within the HPG axis. Black arrows, blue boxes, and green boxes represent other interactions.