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Endocrine Disorder Marijuana Research

 

Endocannabinoids in endocrine and related tumours.

Author information

1
Dipartimento di Scienze Farmaceutiche, Università di Salerno, 84084 Fisciano (Salerno), Italy IEOS, CNR Napoli, 80131 Napoli, Italy.

Abstract

The ‘endocannabinoid system’, comprising the cannabinoid CB1 and CB2 receptors, their endogenous ligands, endocannabinoids and the enzymes that regulate their biosynthesis and degradation, has drawn a great deal of scientist attention during the last two decades. The endocannabinoid system is involved in a broad range of functions and in a growing number of physiopathological conditions. Indeed, recent evidence indicates that endocannabinoids influence the intracellular events controlling the proliferation of numerous types of endocrine and related cancer cells, thereby leading to both in vitro and in vivo antitumour effects. In particular, they are able to inhibit cell growth, invasion and metastasis of thyroid, breast and prostate tumours. The chief events of endocannabinoids in cancer cell proliferation are reported highlighting the correspondent signalling involved in tumour processes: regulation of adenylyl cyclase, cyclic AMP-protein kinase-A pathway and MEK-extracellular signal-regulated kinase signalling cascade.

Endocannabinoids in endocrine and related tumours.

Author information

1
Dipartimento di Scienze Farmaceutiche, Università di Salerno, 84084 Fisciano (Salerno), Italy IEOS, CNR Napoli, 80131 Napoli, Italy.

Abstract

The ‘endocannabinoid system’, comprising the cannabinoid CB1 and CB2 receptors, their endogenous ligands, endocannabinoids and the enzymes that regulate their biosynthesis and degradation, has drawn a great deal of scientist attention during the last two decades. The endocannabinoid system is involved in a broad range of functions and in a growing number of physiopathological conditions. Indeed, recent evidence indicates that endocannabinoids influence the intracellular events controlling the proliferation of numerous types of endocrine and related cancer cells, thereby leading to both in vitro and in vivo antitumour effects. In particular, they are able to inhibit cell growth, invasion and metastasis of thyroid, breast and prostate tumours. The chief events of endocannabinoids in cancer cell proliferation are reported highlighting the correspondent signalling involved in tumour processes: regulation of adenylyl cyclase, cyclic AMP-protein kinase-A pathway and MEK-extracellular signal-regulated kinase signalling cascade.

The role of the endocannabinoid system in the neuroendocrine regulation of energy balance.

Author information

1
INSERM U862, Avenir group Energy Balance and Obesity, Bordeaux, France.

Abstract

Animal and human studies carried out so far have established a role for the endocannabinoid system (ECS) in the regulation of energy balance. Here we critically discuss the role of the endocannabinoid signalling in brain structures, such as the hypothalamus and reward-related areas, and its interaction with neurotransmitter and neuropeptide systems involved in the regulation of food intake and body weight. The ECS has been found to interact with peripheral signals, like leptin, insulin, ghrelin and satiety hormones and the resulting effects on both central and peripheral mechanisms affecting energy balance and adiposity will be described. Furthermore, ECS dysregulation has been associated with the development of dyslipidemia, glucose intolerance and obesity; phenomena that are often accompanied by a plethora of neuroendocrine alterations which might play a causal role in determining ECS dysregulation. Despite the withdrawal of the first generation of cannabinoid type 1 receptor (CB1) antagonists from the pharmaceutical market due to the occurrence of psychiatric adverse events, new evidence suggests that peripherally restricted CB1 antagonists might be efficacious for the treatment of obesity and its associated metabolic disorders. Thus, a perspective on new promising strategies to selectively target the ECS in the context of energy balance regulation is given.

Endocrine effects of marijuana in the male: preclinical studies.

Abstract

Marijuana affects a variety of hormones that are regulated by hypothalamic function and it appears that the psychoactive ingredient, THC, is the major compound responsible for this action. It is probable that THC affects these hormones through its ability to alter various neural transmitters in the hypothalamus or neural transmitters in the CNS which impinge on the hypothalamus. The dopaminergic and serotonergic fibers seem to be particularly important. The two gonadotropins, LH and FSH, secreted by the pituitary gland are of major importance to reproduction in the male. Both gonadotropins appear to respond to a single releasing factor from the hypothalamus, GnRH, which is sensitive to catecholamine neurotransmitters. The THC-induced block of GnRH release results in lowered LH and FSH which is responsible for reduced testosterone production by the Leydig cells of the testis. Other hormones that might have a synergistic or antagonistic effect upon reproduction in the male are the adrenal cortical hormones, prolactin, thyroid hormones, and growth hormones. THC appears to depress prolactin, thyroid gland function, and growth hormone while elevating adrenal cortical steroids. Chronic exposure of laboratory animals, such as rats, mice, and monkeys to marijuana and to the various cannabinoids in marijuana has altered the function of several of the accessory reproductive organs. Reports of reduced prostate and seminal vesicle weights, as well as altered testicular function, have been partially explained by the effect of marijuana in lowering serum testosterone needed for proper function and support. Although some of the change in organ weight may be due to lowered testosterone production by the Leydig cells of the testis, some of the weight changes may be due to a direct action of THC, and perhaps some of the other nonpsychoactive cannabinoids in marijuana, on the tissue themselves. Also, of concern are the reports that acute cannabinoid treatments affects the quality and quantity of spermatozoa produced by the testis. The question is still unanswered as to whether or not the effects observed on spermatozoa are due to a direct action of the cannabinoids on spermatogenesis, or whether some of the observed effects may be due to altered hormone levels which are necessary for the support of spermatogenesis. Reduced testosterone and FSH may be important in producing the observed changes in sperm production by the seminiferous tubules. Many of the effects on the endocrine system caused by chronic treatment of animals with THC are completely reversible with time and there is reason to believe that tolerance develops to these effects with acute exposure to THC.(ABSTRACT TRUNCATED AT 400 WORDS).

PMID:

6090909

Endocrine effects of marijuana.

Author information

1
Division of Endocrinology and Metabolism, Johns Hopkins University, Baltimore, Maryland 21287, USA.

Abstract

In the 35 years since the active compound of marijuana, delta9-tetrahydrocannabinol, was isolated, the psychological and physiological impact of marijuana use has been actively investigated. Animal models have demonstrated that cannabinoid administration acutely alters multiple hormonal systems, including the suppression of the gonadal steroids, growth hormone, prolactin, and thyroid hormone and the activation of the hypothalamic-pituitary-adrenal axis. These effects are mediated by binding to the endogenous cannabinoid receptor in or near the hypothalamus. Despite these findings in animals, the effects in humans have been inconsistent, and discrepancies are likely due in part to the development of tolerance. The long-term consequences of marijuana use in humans on endocrine systems remain unclear.

 

Endocannabinoid system participates in neuroendocrine control of homeostasis.

Author information

1
Centro de Estudios Farmacológicos y Botánicos, CEFYBO-CONICET-UBA, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina. andredelaurentiis@yahoo.com

Abstract

The hypothalamo-neurohypophyseal system plays a role in homeostasis under a variety of stress conditions, including endotoxemia. Oxytocin (OXT) and vasopressin (VP) are important hormones synthesized by neurons in the hypothalamic paraventricular and supraoptic nuclei and released into different brain regions and from the neurohypophyseal terminals into the blood in response to many patho-physiological stimuli. However, the mechanism that controls OXT and VP secretion has not been fully elucidated. Nitric oxide (NO) is a known mediator that regulates the release of these hormones. The endocannabinoid system is a new intercellular system that modulates several neuroendocrine actions. Endocannabinoids (eCB) are released as retrograde messengers by many neurons, including hypothalamic magnocellular neurons and cannabinoid receptors are localized within these neurons, as well as in the anterior and posterior pituitary lobes, suggesting an eCB role in the production and release of OXT and VP. Lipopolysaccharide (LPS) injection is a model used as immune challenge. LPS causes a neuroendocrine response that is mediated by cytokines, tumor necrosis factor-alpha being one of them. We focused on NO and endocannabinoid system participation on OXT and VP production and secretion during basal and stress conditions and found that eCB affect basal OXT and VP secretion by acting differently at each level of the hypothalamo-neurohypophyseal system. After LPS, there is an increase in eCB synthesis that enhances OXT secretion.

The emerging role of the endocannabinoid system in endocrine regulation and energy balance.

Author information

1
Endocrinology Unit, Department of Internal Medicine and Gastroenterology, Sant’ Orsola-Malpighi Hospital, Bologna, Italy, and Department of Physiological Chemistry, Johannes Gutenberg-University Mainz, Germany. pagube@med.unibo.it

Abstract

During the last few years, the endocannabinoid system has emerged as a highly relevant topic in the scientific community. Many different regulatory actions have been attributed to endocannabinoids, and their involvement in several pathophysiological conditions is under intense scrutiny. Cannabinoid receptors, named CB1 receptor and CB2 receptor, first discovered as the molecular targets of the psychotropic component of the plant Cannabis sativa, participate in the physiological modulation of many central and peripheral functions. CB2 receptor is mainly expressed in immune cells, whereas CB1 receptor is the most abundant G protein-coupled receptor expressed in the brain. CB1 receptor is expressed in the hypothalamus and the pituitary gland, and its activation is known to modulate all the endocrine hypothalamic-peripheral endocrine axes. An increasing amount of data highlights the role of the system in the stress response by influencing the hypothalamic-pituitary-adrenal axis and in the control of reproduction by modifying gonadotropin release, fertility, and sexual behavior. The ability of the endocannabinoid system to control appetite, food intake, and energy balance has recently received great attention, particularly in the light of the different modes of action underlying these functions. The endocannabinoid system modulates rewarding properties of food by acting at specific mesolimbic areas in the brain. In the hypothalamus, CB1 receptor and endocannabinoids are integrated components of the networks controlling appetite and food intake. Interestingly, the endocannabinoid system was recently shown to control metabolic functions by acting on peripheral tissues, such as adipocytes, hepatocytes, the gastrointestinal tract, and, possibly, skeletal muscle. The relevance of the system is further strenghtened by the notion that drugs interfering with the activity of the endocannabinoid system are considered as promising candidates for the treatment of various diseases, including obesity.

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