Alcohol inhibits luteinizing hormone-releasing hormone release by activating the endocannabinoid system

Fernández‐Solari, Javier; Scorticati, Camila; Mohn, Claudia; Laurentiis, Andrea De; Billi, Silvia; Franchi, A.M.; McCann, Samuel M.; Rettori, Valéria

doi:10.1073/pnas.0307346101

Cited by 34 publications

(33 citation statements)

References 37 publications

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“…Furthermore, we have recently demonstrated that AEA inhibits the forskolin-stimulated LHRH release in male rats (16). In the present work we observed that AEA inhibited LHRH release from MBH of males but had no effect on the hypothalamic LHRH release in OVX rats.…”

Section: Discussionsupporting

confidence: 58%

“…We have recently demonstrated in male rats that AEA increased the release of GABA, a neurotransmitter involved in the inhibition of LHRH release (16). Thus, a stimulation of GABA release could be involved in the inhibition of basal LHRH release by AEA in males.…”

Section: Discussionmentioning

confidence: 93%

“…Synthase activity in MBH was assayed as described by Fernández-Solari et al (16). In brief, the MBH were homogenized in 200 l of buffer (20 mM Tris⅐HCl͞1 mM EDTA, pH 7.6) and centrifuged 2,000 ϫ g for 15 min.…”

Section: Methodsmentioning

confidence: 99%

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The inhibitory effect of anandamide on luteinizing hormone-releasing hormone secretion is reversed by estrogen

Scorticati

Fernández‐Solari

Laurentiis

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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Because ⌬-9-tetrahydrocannabinol (THC) inhibited luteinizing hormone-releasing hormone (LHRH) in male rats, we hypothesized that the endocannabinoid, anandamide (AEA), would act similarly. AEA microinjected intracerebroventricularly (i.c.v.) decreased plasma luteinizing hormone (LH) at 30 min in comparison to values in controls (P < 0.001). The cannabinoid receptor 1 (CB1-r)-specific antagonist, [N-(piperidin-1-yl)-1-(2,4-dichlorophenyl)-5-(4-chlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide] (AM251), produced a significant elevation in plasma LH (P < 0.01). AEA (10 ؊9 M) decreased LHRH release from medial basal hypothalami incubated in vitro. These results support the concept that endogenous AEA inhibits LHRH followed by decreased LH release in male rats. In ovariectomized (OVX) female rats, AEA i.c.v. also inhibited LH release, but in this case AM251 had an even greater inhibitory effect than AEA. In vitro, AEA had no effect on LHRH in OVX rats. It seems that endogenous AEA inhibits LHRH followed by decreased LH release in OVX rats but that AM251 has an inhibitory action in this case. In striking contrast, in OVX, estrogen-primed (OVX-E) rats, AEA i.c.v. instead of decreasing LH, increased its release. This effect was completely blocked by previous injection of AM251. When medial basal hypothalami of OVX-E rats were incubated, AEA increased LHRH release. The synthesized AEA was higher in OVX-E rats than in OVX and males, indicating that estrogen modifies endocannabinoid levels and effects. The results are interpreted to mean that sex steroids have profound effects to modify the response to AEA. It inhibits LHRH and consequently diminishes LH release in males and OVX females, but stimulates LHRH followed by increased LH release in OVX-E-primed rats.AM251 ͉ CB1 receptor ͉ medial basal hypothalamus I t is well known that ⌬-9-tetrahydrocannabinol (THC), the active principle isolated from Cannabis sativa, alters many reproductive parameters in both male and female laboratory animals and humans (1). It has been reported that THC decreases secretion of hormones that control reproduction in male rats (2) but on the other hand stimulates sexual behavior in female rats (3). Also, a marked depression within 1 h in luteinizing hormone (LH) secretion after THC administration has been reported in male rats (2, 4). The molecular target for the action of this plant-derived cannabinol is the endocannabinoid system. This endogenous system consists of two types of GTP-binding protein-coupled receptors, cannabinoid receptors type 1 (CB1-r) and cannabinoid receptors type 2, and their endogenous ligands named anandamide (AEA) and 2-arachidonyl glycerol (5). This endocannabinoid system plays modulatory roles in many processes of the brain, such as the regulation of appetite, temperature, memory, and sexual and motor behavior (6). The activation of the endocannabinoid system acts in series with changes in the activity of several neurotransmitters including ␥-aminobutyric acid (GABA), dopamine, and glutamate (7).We had previously demon...

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Section: Discussionsupporting

confidence: 58%

Section: Discussionmentioning

confidence: 93%

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The inhibitory effect of anandamide on luteinizing hormone-releasing hormone secretion is reversed by estrogen

Scorticati

Fernández‐Solari

Laurentiis

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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“…Postsynaptic GABA receptors, located on GnRH neurons, are not activated, and as a consequence, GnRH is not released. Interestingly enough, the inhibitory effect of AEA was higher than that of 2-AG [58,59]. Olah and coworkers postulated that the difference between the effects of AEA and 2-AG on the serum levels of LH is due to the difference in receptor activation as AEA can activate both CB1 and TRPV1 receptors while 2-AG acts only on the CB1 receptor [60].…”

Section: Ecs and The Hypothalamus-pituitary-gonadal Axismentioning

confidence: 99%

Marijuana, phytocannabinoids, the endocannabinoid system, and male fertility

Plessis

Agarwal

Syriac

2015

J Assist Reprod Genet

126

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Marijuana has the highest consumption rate among all of the illicit drugs used in the USA, and its popularity as both a recreational and medicinal drug is increasing especially among men of reproductive age. Male factor infertility is on the increase, and the exposure to the cannabinoid compounds released by marijuana could be a contributing cause. The endocannabinoid system (ECS) is deeply involved in the complex regulation of male reproduction through the endogenous release of endocannabinoids and binding to cannabinoid receptors. Disturbing the delicate balance of the ECS due to marijuana use can negatively impact reproductive potential. Various in vivo and in vitro studies have reported on the empirical role that marijuana plays in disrupting the hypothalamus-pituitary-gonadal axis, spermatogenesis, and sperm function such as motility, capacitation, and the acrosome reaction. In this review, we highlight the latest evidence regarding the effect of marijuana use on male fertility and also provide a detailed insight into the ECS and its significance in the male reproductive system.

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“…Having demonstrated the presence of CB1 receptors in the MBH, we studied the effect of AEA on LHRH release. Firstly, we showed that AEA (10 -9 M ) decreased by 70% the N-methyl D -aspartic acid (NMDA)-stimulated LHRH release from MBH incubated in vitro [10] . Secondly, we demonstrated that the same concentration of AEA significantly decreased the forskolin (FRSK)-induced cyclic AMP (cAMP) content and LHRH release.…”

Section: Endocannabinoids In Tnf-mentioning

confidence: 98%

Endocannabinoids in TNF-α and Ethanol Actions

Rettori

Fernández‐Solari²,

Prestifilippo³

et al. 2007

Neuroimmunomodulation

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During marijuana and alcohol consumption as well as during inflammation the reproductive axis is inhibited, mainly through the inhibition of luteinizing hormone-releasing hormone release. In male rats, this inhibitory effect is mediated, at least in part, by the activation of hypothalamic cannabinoid type 1 receptors (CB1). During inflammation, this activation of the endocannabinoid system seems to be mediated by an increase in TNF-α production followed by anandamide augmentations, similarly the effect of intragastric administration of ethanol (3 g/kg) seems to be due to an increase in anandamide. On the other hand, a number of different actions mediated by the endocannabinoid system in various organs and tissues have been described. Both cannabinoid receptors, CB1 and CB2, are localized in the submandibular gland where they mediate the inhibitory effect of intrasubmandibular injections of the endocannabinoid anandamide (6 × 10^–5M) on salivary secretion. Lipopolysaccharide (5 mg/kg/3 h) injected intraperitoneally and ethanol (3 g/kg/1 h) injected intragastrically inhibited the salivary secretion induced by the sialogogue metacholine; this inhibitory effect was blocked by CB1 and/or CB2 receptor antagonists. Similar to the hypothalamus, these effects seem to be mediated by increased anandamide. In summary, similar mechanisms mediate the inhibitory actions of endocannabinoids and cannabinoids in both hypothalamus and submandibular gland during drug consumption and inflammation.

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Alcohol inhibits luteinizing hormone-releasing hormone release by activating the endocannabinoid system

Cited by 34 publications

References 37 publications

The inhibitory effect of anandamide on luteinizing hormone-releasing hormone secretion is reversed by estrogen

The inhibitory effect of anandamide on luteinizing hormone-releasing hormone secretion is reversed by estrogen

Marijuana, phytocannabinoids, the endocannabinoid system, and male fertility

Endocannabinoids in TNF-α and Ethanol Actions

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