title: Hypothalamus-pituitary axis: an obligatory target for endocannabinoids to inhibit steroidogenesis in frog testis.
abstract: Endocannabinoids - primarily anandamide (AEA) and 2-arachidonoylglycerol (2-AG) - are lipophilic molecules that bind to cannabinoid receptors (CB1 and CB2). They affect neuroendocrine activity inhibiting gonadotropin releasing hormone (GnRH) secretion and testosterone production in rodents, through a molecular mechanism supposed to be hypothalamus dependent. In order to investigate such a role, we choose the seasonal breeder, the anuran amphibian Rana esculenta, an experimental model in which components of the endocannabinoid system have been characterized. In February, at the onset of a new spermatogenetic wave, we carried out in vitro incubations of frog testis with AEA, at 10(-9)M dose. Such a treatment had no effect on the expression of cytochrome P450 17alpha hydroxylase/17,20 lyase (cyp17) nor 3-β-hydroxysteroid dehydrogenase/Δ-5-4 isomerase (3β-HSD), key enzymes of steroidogenesis. To understand whether or not the functionality of the hypothalamus-pituitary axis could be essential to support the role of endocannabinoids in steroidogenesis, frogs were injected with AEA, at 10(-8)M dose. Differently from in vitro experiment, the in vivo administration of AEA reduced the expression of cyp17 and 3β-HSD. Whereas the effect on 3β-HSD was counteracted by SR141716A (Rimonabant) - a selective antagonist of CB1, thus indicating a CB1 dependent modulation - the effect on cyp17 was not, suggesting a possible involvement of receptors other than CB1, probably the type-1 vanilloid receptor (TRPV1), since AEA works as an endocannabinoid and an endovanilloid as well. In conclusion our results indicate that endocannabinoids, via CB1, inhibit the expression of 3β-HSD in frog testis travelling along the hypothalamus-pituitary axis.
authors.affiliation: Dipartimento di Medicina Sperimentale, Seconda Università degli Studi di Napoli, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Chianese
authors.affiliation: Dipartimento di Medicina Sperimentale, Seconda Università degli Studi di Napoli, Italy.
authors.forename: Vincenza
authors.initials: V
authors.lastname: Ciaramella
authors.affiliation: Dipartimento di Medicina Sperimentale, Seconda Università degli Studi di Napoli, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Fasano
authors.affiliation: Dipartimento di Medicina Sperimentale, Seconda Università degli Studi di Napoli, Italy. Electronic address: riccardo.pierantoni@unina2.it.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Pierantoni
authors.affiliation: Dipartimento di Scienze Motorie e del Benessere, Università di Napoli Parthenope, Italy.
authors.forename: Rosaria
authors.initials: R
authors.lastname: Meccariello
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D063388:Endocannabinoids / Q000494:pharmacology*; D005989:Glycerides / Q000494:pharmacology*; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D011893:Rana esculenta / Q000378:metabolism*; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism; D013256:Steroids / Q000096:biosynthesis* / Q000737:chemistry; D013737:Testis / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D013739:Testosterone / Q000096:biosynthesis / Q000737:chemistry
chemical_list: D001095:Arachidonic Acids; D018076:DNA, Complementary; D063388:Endocannabinoids; D005989:Glycerides; D053284:Polyunsaturated Alkamides; D043884:Receptor, Cannabinoid, CB1; D013256:Steroids; D013739:Testosterone; C094503:glyceryl 2-arachidonate; D015096:3-Hydroxysteroid Dehydrogenases; D013254:Steroid 17-alpha-Hydroxylase; C078814:anandamide
keywords: Amphibian; Endocannabinoid system; Spermatogenesis; Steroidogenesis