Endocannabinoids and the Endocrine System in Health and Disease

Hillard, Cecilia J.

doi:10.1007/978-3-319-20825-1_11

Cited by 34 publications

(19 citation statements)

References 153 publications

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“…As a consequence, subsequent CORT production is elevated in response to a given amount of ACTH. There is also evidence for adrenal CORT production to be regulated by adrenal endocannabinoid function (221). …”

Section: Experimental Manipulation Of the Hpa Axismentioning

confidence: 99%

A users guide to HPA axis research

Spencer

Deak

2017

Physiology & Behavior

288

180

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Glucocorticoid hormones (cortisol and corticosterone - CORT) are the effector hormones of the hypothalamic-pituitary-adrenal (HPA) axis neuroendocrine system. CORT is a systemic intercellular signal whose level predictably varies with time of day and dynamically increases with environmental and psychological stressors. This hormonal signal is utilized by virtually every cell and physiological system of the body to optimize performance according to circadian, environmental and physiological demands. Disturbances in normal HPA axis activity profiles are associated with a wide variety of physiological and mental health disorders. Despite numerous studies to date that have identified molecular, cellular and systems-level glucocorticoid actions, new glucocorticoid actions and clinical status associations continue to be revealed at a brisk pace in the scientific literature. However, the breadth of investigators working in this area poses distinct challenges in ensuring common practices across investigators, and a full appreciation for the complexity of a system that is often reduced to a single dependent measure. This Users Guide is intended to provide a fundamental overview of conceptual, technical and practical knowledge that will assist individuals who engage in and evaluate HPA axis research. We begin with examination of the anatomical and hormonal components of the HPA axis and their physiological range of operation. We then examine strategies and best practices for systematic manipulation and accurate measurement of HPA axis activity. We feature use of experimental methods that will assist with better understanding of CORT’s physiological actions, especially as those actions impact subsequent brain function. This research approach is instrumental for determining the mechanisms by which alterations of HPA axis function may contribute to pathophysiology.

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Section: Experimental Manipulation Of the Hpa Axismentioning

confidence: 99%

A users guide to HPA axis research

Spencer

Deak

2017

Physiology & Behavior

288

180

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“…THC has been shown to have a pronounced regulatory effect on the hypothalamic-pituitary-gonadal axis (Hillard, 2015). As marijuana laws undergo reform, with the prevalence of marijuana use expected to rise further (Cerda et al, 2012), the potential effects of marijuana on male reproductive health requires further elucidation.…”

Section: Introductionmentioning

confidence: 99%

“…Marijuana may be related to reproductive health because of changes in circulating hormones, through tetrahydrocannabinol (THC), the principal active component of marijuana, which binds to cannabinoid system receptors (du Plessis et al, 2015). THC has been shown to have a pronounced regulatory effect on the hypothalamic-pituitary-gonadal axis (Hillard, 2015). As marijuana laws undergo reform, with the prevalence of marijuana use expected to rise further (Cerda et al, 2012), the potential effects of marijuana on male reproductive health requires further elucidation.…”

Section: Introductionmentioning

confidence: 99%

Marijuana use and serum testosterone concentrations among U.S. males

et al. 2017

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Background Marijuana has been reported to have several effects on the male reproductive system. Marijuana has previously been linked to reduced adult testosterone, however, a study in Denmark reported increased testosterone concentrations among marijuana users. This study was performed to estimate the effect of marijuana use on testosterone in U.S. males. Methods Data on serum testosterone, marijuana use and covariates for 1577 men from the 2011–2012 U.S. National Health and Nutrition Examination Survey (NHANES) were analyzed. Information on marijuana use was collected by a self-administered computer-assisted questionnaire. Serum testosterone was determined using isotope dilution liquid chromatography tandem mass spectrometry. The effects of marijuana use on serum testosterone concentrations were examined by frequency, duration, and recency of use. Adjusted means and 95% confidence intervals (CI) of serum testosterone across levels of marijuana use were estimated using multiple linear regression weighted by the survey weights. Results The majority (66.2%) of the weighted study population reported ever using marijuana with 26.6% reporting current marijuana use. There was no difference in serum testosterone between ever users (adjusted mean = 3.69 ng/mL, 95% CI: 3.46, 3.93) and never users (adjusted mean = 3.70 ng/mL, 95% CI: 3.45, 3.98) upon multivariable analysis. However, serum testosterone was inversely associated with time since last regular use of marijuana (p-value for trend = 0.02). When restricted to men aged 18 – 29 years, this relationship strengthened (p-value for trend < 0.01) and serum testosterone was also inversely associated with time since last use (p-value for trend < 0.01), indicating that recency of use, and not duration or frequency, had the strongest relationship with testosterone levels. Discussion Serum testosterone concentrations were higher in men with more recent marijuana use. Studies are needed to determine the extent to which circulating testosterone concentrations mediate the relationship of marijuana use to male reproductive outcomes.

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“…Similarly, the selective pharmacological inhibition of CB1R and CB2R in early embryos resulted in altered development of the locomotor system at later stages [31], and treatment with ∆9-THC or CBD resulted in altered motor neurons morphology, synaptic activity at the neuromuscular junction and locomotor responses to sound [32]. Reducing the level of 2-AG via knockdown of Daglα resulted in abnormal behaviors, characterized by stereotyped movement and altered motion perception [33].Few reports have linked the eCB/CB1R signaling functions to the maturation and physiology of the hypothalamic neuroendocrine systems controlling reproduction and appetite [34][35][36]. The gonadotropin releasing hormone (GnRH) neurons, which are central for the control of sexual maturation, fertility and reproduction, have been extensively studied.…”

mentioning

confidence: 99%

“…In this context, eCBs have been shown to modulate the input and the firing activity of GnRH neurons [36], and CB1R activation inhibits presynaptic GABA release [37,38]. Accordingly, the literature reports a link between perturbations of CB1R (either due to consumption of phyto-cannabinoids or exposure to synthetic cannabinoids) and altered functionality of the neuroendocrine gonadotropic system, puberty and fertility deficits [35,36].…”

mentioning

confidence: 99%

Interference with the Cannabinoid Receptor CB1R Results in Miswiring of GnRH3 and AgRP1 Axons in Zebrafish Embryos

Zuccarini

D’Atri

Cottone

et al. 2019

IJMS

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The G protein-coupled cannabinoid receptors type 1 (CB1R) and type 2 (CB2R), and their endocannabinoid (eCBs) ligands, have been implicated in several aspects of brain wiring during development. Here we aim to assess whether interfering with CB1R affects development, neuritogenesis and pathfinding of GnRH and AgRP neurons, forebrain neurons that control respectively reproduction and appetite. We pharmacologically and genetically interfered with CB1R in zebrafish strains with fluorescently labeled GnRH3 and the AgRP1 neurons. By applying CB1R antagonists we observed a reduced number of GnRH3 neurons, fiber misrouting and altered fasciculation. Similar phenotypes were observed by CB1R knockdown. Interfering with CB1R also resulted in a reduced number, misrouting and poor fasciculation of the AgRP1 neuron’s axonal projections. Using a bioinformatic approach followed by qPCR validation, we have attempted to link CB1R functions with known guidance and fasciculation proteins. The search identified stathmin-2, a protein controlling microtubule dynamics, previously demonstrated to be coexpressed with CB1R and now shown to be downregulated upon interference with CB1R in zebrafish. Together, these results raise the likely possibility that embryonic exposure to low doses of CB1R-interfering compounds could impact on the development of the neuroendocrine systems controlling sexual maturation, reproduction and food intake.

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Endocannabinoids and the Endocrine System in Health and Disease

Cited by 34 publications

References 153 publications

A users guide to HPA axis research

A users guide to HPA axis research

Marijuana use and serum testosterone concentrations among U.S. males

Interference with the Cannabinoid Receptor CB1R Results in Miswiring of GnRH3 and AgRP1 Axons in Zebrafish Embryos

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