Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P21554 (cannabinoid receptor)
 3,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study was to test whether the recently described endogenous ligand for the cannabinoid receptor; arachidonyl-ethanolamide (anandamide, ANA), may produce similar effects on pregnancy as the main psychoactive component of marihuana: delta9-tetrahydrocannabinol (THC) in rats. ANA, THC (0.02 mg/kg i.p./day, respectively) or vehicle were injected daily over the third week of pregnancy. The pregnant rats were either killed on day 21 of pregnancy or followed up to delivery. Results show a significant increase in the duration of pregnancy after both THC and ANA treatment. Both drugs caused an increase in the frequency of stillbirths. The mothers' hormone contents in tissues and sera were measured. Decreased LH content was observed in the serum of treated animals. No changes in FSH content were observed either in the pituitary or in the sera. Pituitary prolactin (PRL) levels was lower in ANA treated animals as compared both to controls or THC treated subjects. The serum PRL content decreased in all experimental groups. Decrease in serum progesterone was more prominent in treated rats. Serum levels of prostaglandins (PGF 1alpha and PGF 2alpha) were significantly decreased after THC and ANA treatment. We conclude that ANA has the same tendency to change reproductory parameters in pregnant rats as THC, although in some cases the effects of ANA were slightly different from that of THC. Both endogenous and exogenous cannabinoids inhibit PG synthesis in pregnant rats and this maybe responsible for the delay constitute the mechanism in the onset of labour.
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PMID:Effects of anandamide on gestation in pregnant rats. 919 80

Anandamide (AEA), a prominent member of the endogenous ligands of cannabinoid receptors (endocannabinoids), is known to adversely affect female fertility. However, a potential role of AEA in male reproductive functions is unknown. Here we report evidence that immature mouse Sertoli cells have the biochemical tools to bind and inactivate AEA, i.e. a functional type-2 cannabinoid receptor (CB2R), a selective AEA membrane transporter, and an AEA-degrading enzyme fatty acid amide hydrolase. We show that, unlike CB2R, the activity of AEA membrane transporter and the activity and expression of FAAH decrease, whereas the apoptosis-inducing activity of AEA increases with age during the neonatal period. We also show that FSH reduces the apoptotic potential of AEA, but not that of its nonhydrolyzable analog methanandamide. Concomitantly, FSH enhances FAAH activity in a manner dependent on mRNA transcription and protein synthesis and apparently involving cAMP. These data demonstrate that Sertoli cells partake in the peripheral endocannabinoid system, and that FSH reduces the apoptotic potential of AEA by activating FAAH. Taken together, it can be suggested that the endocannabinoid network plays a role in the hormonal regulation of male fertility.
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PMID:Anandamide activity and degradation are regulated by early postnatal aging and follicle-stimulating hormone in mouse Sertoli cells. 1248 26

The type 1-cannabinoid receptor, CNR1, regulates differentiation of spermatids. Indeed, we have recently reported that the genetic inactivation of Cnr1 in mice influenced chromatin remodeling of spermatids, by reducing histone displacement and then sperm chromatin quality indices (chromatin condensation and DNA integrity). Herein, we have studied, at both central and testicular levels, the molecular signals potentially involved in histone displacement. In particular, investigation of the neuroendocrine axis involved in estrogen production demonstrated down-regulation of the axis supporting FSH/estrogen secretion in Cnr1-knockout male mice. Conversely, Cnr1-knockout male mice treated with 17beta-estradiol showed a weak increase of pituitary Fsh-beta subunit mRNA levels and a rescue of sperm chromatin quality indices demonstrating that estrogens, possibly in combination with FSH secretion, play an important role in regulating chromatin remodeling of spermatids.
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PMID:Low 17beta-estradiol levels in CNR1 knock-out mice affect spermatid chromatin remodeling by interfering with chromatin reorganization. 2367 85

Ovarian steroidogenesis is embedded in a sensitive network of regulatory mechanisms crucial for human fertility. The endocannabinoid system (ECS) represents an intrinsic modulating system involved in the regulation of endocrine functions. In the present study we characterized the ECS in the human granulosa cell line KGN and its impact on gonadotropin sensitivity and steroid hormone synthesis under basal and FSH-stimulated conditions. Expression studies were performed and estradiol was measured. CB1, CB2, DAGL, FAAH, GPR55, MAGL, NAPE-PLD and TRPV1 were expressed without FSH-dependent effects. Treatment with selective cannabinoid receptor agonists reduced basal but not FSH-stimulated estradiol and CYP19. Progesterone was not altered by ECS manipulation. CB1 agonist changed the expression of miRNAs associated with granulosa cell function, e.g. miR-23a, miR-24, miR-181a and miR-320a. Present data indicate a modulating role of the intrinsic ovarian ECS in the regulation of estradiol synthesis.
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PMID:The endocannabinoid system in the human granulosa cell line KGN. 2677 29