Overlapping molecular pathways between cannabinoid receptors type 1 and 2 and estrogens/androgens on the periphery and their involvement in the pathogenesis of common diseases (Review)

Abstract

The physiological and pathophysiological roles of sex hormones have been well documented and the modulation of their effects is applicable in many current treatments. On the other hand, the physiological role of endocannabinoids is not yet clearly understood and the endocannabinoid system is considered a relatively new therapeutic target. The physiological association between sex hormones and cannabinoids has been investigated in several studies; however, its involvement in the pathophysiology of common human diseases has been studied separately. Herein, we present the first systematic review of molecular pathways that are influenced by both the cannabinoids and sex hormones, including adenylate cyclase and protein kinase A, epidermal growth factor receptor, cyclic adenosine monophosphate response element-binding protein, vascular endothelial growth factor, proto-oncogene serine/threonine-protein kinase, mitogen-activated protein kinase, phosphatidylinositol-4,5-bisphosphate 3-kinase, C-Jun N-terminal kinase and extracellular-signal-regulated kinases 1/2. Most of these influence cell proliferative activity. Better insight into this association may prove to be beneficial for the development of novel pharmacological treatment strategies for many common diseases, including breast cancer, endometrial cancer, prostate cancer, osteoporosis and atherosclerosis. The associations between cannabinoids, estrogens and androgens under these conditions are also presented and the molecular interactions are highlighted.

<p>Cannabidiol as a Novel Therapeutic for Immune Modulation</p>

“… 19 Studies have also shown that activation of the CB 1 receptor also leads to regulation of mitogen-activated protein kinases (MAPKs) that are vital to inflammatory and immune cellular responses, including extracellular signal-regulated protein kinase 1/2 (ERK1/2), p38, and c-jun terminal kinase (JNK). 20 , 21 The phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) is a third pathway involved in cell growth and survival that may also be activated by CB 1 receptor. 22 , 23 Similarly, CB 2 receptor agonism modulates and inhibits AC and cAMP leading to the inactivation of PKA by G i/o protein coupling.…”

Cannabinoids and Hormone Receptor-Positive Breast Cancer Treatment

“…There is evidence that molecular pathways between CBRs and estrogens overlap, and this could impact pathogenesis of common diseases, including HR+ BC [38]. Most of the preclinical studies have explored the effects of cannabinoids on BC cell lines.…”

A new ESI-LC/MS approach for comprehensive metabolic profiling of phytocannabinoids in Cannabis

“…Their pharmacological effects have been found to be mediated mainly through two specific plasma membrane G-protein-coupled receptors, referred to as cannabinoid receptors CB1 and CB2. Today, more receptors of the endocannabinoid system are known, including GPR55, GPR119 and TRPV1, however their physiological functions are still mostly unknown 12 – 16 . In addition it is widely accepted today that different cannabinoids act on multiple targets 17 , 18 .…”