title: Expression of type-1 cannabinoid receptor during rat postnatal testicular development: possible involvement in adult leydig cell differentiation.
abstract: Endocannabinoids are lipidic modulators able to bind cannabinoid receptors (CNRs). Two types of CNRs have been cloned, CNR1 (central) and CNR2 (peripheral). The objectives of the present study were to investigate the expression pattern of CNR1 in the rat testis during prepubertal development and to define the CNR1 spatiotemporal pattern. From 31 to 60 days of age, CNR1 was immunolocalized in round elongating spermatids and spermatozoa, suggesting an important role for this receptor in spermatogenesis. From 14 to 60 days of age, adult Leydig cells (ALCs) at different developmental stages were positive for CNR1. In particular, CNR1 expression in differentiating ALCs was negatively correlated to cell division. Bromodeoxyuridine uptake experiments on serial sections showed that immature Leydig cells in mitosis were negative for CNR1; in contrast, immature nonmitotic Leydig cells were positive for CNR1. A further observation of few ALCs in CNR1KO mice validates the role of CNR1 during proliferative activity involved in ALC differentiation. In addition, starting from 41 days of age, a faint CNR1 signal was also observed in Sertoli cells. Taken together, these results demonstrate the first clear evidence (to our knowledge) of CNR1 in mammalian germinal epithelium, ALCs, and Sertoli cells and indicate that differentiation of ALCs may depend on the endocannabinoid system.
authors.affiliation: Dipartimento di Medicina Sperimentale, Seconda Università degli Studi di Napoli, 80138 Napoli, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Cacciola
authors.forename: Teresa
authors.initials: T
authors.lastname: Chioccarelli
authors.forename: Ken
authors.initials: K
authors.lastname: Mackie
authors.forename: Rosaria
authors.initials: R
authors.lastname: Meccariello
authors.forename: Catherine
authors.initials: C
authors.lastname: Ledent
authors.forename: Silvia
authors.initials: S
authors.lastname: Fasano
authors.forename: Riccardo
authors.initials: R
authors.lastname: Pierantoni
authors.forename: Gilda
authors.initials: G
authors.lastname: Cobellis
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D007985:Leydig Cells / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D013094:Spermatozoa / Q000378:metabolism; D013737:Testis / Q000254:growth & development* / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D043884:Receptor, Cannabinoid, CB1