Endocannabinoids are Involved in Male Vertebrate Reproduction: Regulatory Mechanisms at Central and Gonadal Level.
Endocannabinoids (eCBs) are natural lipids regulating a large array of physiological functions and behaviors in vertebrates. The eCB system is highly conserved in evolution and comprises several specific receptors (type-1 and type-2 cannabinoid receptors), their endogenous ligands (e.g., anandamide and 2-arachidonoylglycerol), and a number of biosynthetic and degradative enzymes. In the last few years, eCBs have been described as critical signals in the control of male and female reproduction at multiple levels: centrally, by targeting hypothalamic gonadotropin-releasing-hormone-secreting neurons and pituitary, and locally, with direct effects on the gonads. These functions are supported by the extensive localization of cannabinoid receptors and eCB metabolic enzymes at different levels of the hypothalamic-pituitary-gonadal axis in mammals, as well as bonyfish and amphibians. In vivo and in vitro studies indicate that eCBs centrally regulate gonadal functions by modulating the gonadotropin-releasing hormone-gonadotropin-steroid network through direct and indirect mechanisms. Several proofs of local eCB regulation have been found in the testis and male genital tracts, since eCBs control Sertoli and Leydig cells activity, germ cell progression, as well as the acquisition of sperm functions. A comparative approach usually is a key step in the study of physiological events leading to the building of a general model. Thus, in this review, we summarize the action of eCBs at different levels of the male reproductive axis, with special emphasis, where appropriate, on data from non-mammalian vertebrates.
Department of Life Sciences and Systems Biology, University of Turin , Turin , Italy ; Neuroscience Institute of Turin, University of Turin , Turin , Italy.
Patrizia
P
Bovolin
Department of Life Sciences and Systems Biology, University of Turin , Turin , Italy.
Erika
E
Cottone
Department of Life Sciences and Systems Biology, University of Turin , Turin , Italy.
Valentina
V
Pomatto
Dipartimento di Medicina Sperimentale, Seconda Università di Napoli , Naples , Italy.
Silvia
S
Fasano
Dipartimento di Medicina Sperimentale, Seconda Università di Napoli , Naples , Italy.
Riccardo
R
Pierantoni
Dipartimento di Medicina Sperimentale, Seconda Università di Napoli , Naples , Italy.
Gilda
G
Cobellis
Dipartimento di Scienze Motorie e del Benessere, Università di Napoli Parthenope , Naples , Italy.
Rosaria
R
Meccariello
GnRH; chromatin remodeling; hypothalamus; male fertility; pituitary; spermatogenesis