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BOR - Papers in Press, published online ahead of print July 9, 2008.
Biol Reprod 2008, 10.1095/biolreprod.108.070128
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BIOLOGY OF REPRODUCTION 79, 758–765 (2008)
DOI: 10.1095/biolreprod.108.070128
© 2008 by the Society for the Study of Reproduction, Inc.

Expression of Type-1 Cannabinoid Receptor During Rat Postnatal Testicular Development: Possible Involvement in Adult Leydig Cell Differentiation1

Giovanna Cacciola 3, Teresa Chioccarelli 3, Ken Mackie 4, Rosaria Meccariello 5, Catherine Ledent 6, Silvia Fasano 3, Riccardo Pierantoni 2 3, and Gilda Cobellis 3

Dipartimento di Medicina Sperimentale,3 Seconda Università degli Studi di Napoli, 80138 Napoli, Italy Department of Psychological and Brain Sciences,4 Indiana University, Bloomington, Indiana 47405 Dipartimento di Studi Delle Istituzioni Dei Sistemi Territoriali,5 Università "Parthenope" di Napoli, 80133 Napoli, Italy Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire,6 Université Libre de Bruxelles, Campus Erasme, 1050 Brussels, Belgium

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.

CNR1, endocannabinoid system, Leydig cells, prepubertal development, testis

FOOTNOTES

1Supported by grants from PRIN and Regione Campania (legge 5) and by a fellowship from Istituto Nazionale Biostrutture e Biosistemi to G. Cacciola.

Correspondence: 2Riccardo Pierantoni, Dipartimento di Medicina Sperimentale, Seconda Università degli Studi di Napoli, 80138 Napoli, Italy. FAX: 39 081 566 7536; e-mail: riccardo.pierantoni{at}unina2.it






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Copyright © 2008 by the Society for the Study of Reproduction.