3. Umbruch 4.4..2005 - Online Pot

Endocannabinoids and regulation of fertility 75
An interesting observation is that AEA can force Sertoli cells to apoptosis,
and that this process is more evident upon ageing [41]. The pro-apoptotic
effect of AEA is not mediated by CB 1,CB 2 or so-called endothelial-type
cannabinoid receptors, nor by vanilloid receptors. Instead, CB 2 receptors
expressed by Sertoli cells have a protective role against the toxic effects of
AEA, and so does FSH. In fact, this hormone dose-dependently inhibits apoptosis
by inducing a remarkable (approximately 5-fold) increase in FAAH activity
[41]. Therefore, it can be suggested that altered levels of FSH can affect
testis development through the control of the pro-apoptotic potential of AEA.
This observation, together with the well-established relationship of Sertoli cell
number to the total spermatogenic output of the testis, can contribute to the
negative effects exerted on testicular development by altered FSH concentrations,
as well as by mutations of the FSH receptor gene [45]. Overall, the finding
that Sertoli cells partake in the peripheral endocannabinoid system may
open new perspectives to the understanding and treatment of male infertility.
In particular, the observation that FAAH modulates the biological effects of
AEA on Sertoli cells, and that this FAAH-mediated control is under hormonal
regulation, extends to male reproduction the concept that AEA hydrolase is
an important check-point, as described above for female fertility.
Conclusions and perspectives
Available evidence clearly shows that in mammals endocannabinoid signalling
is intimately associated with embryo–uterine interactions during implantation.
The exact physiological significance of this signalling pathway is not yet clear,
and it is not known how widespread it might be among different species. At
any rate, in humans low FAAH in lymphocytes correlates with spontaneous
abortion, calling for attention on this enzyme as a key point in the control of
the endocannabinoid system during pregnancy [29–32]. Moreover, available
evidence seems to add endocannabinoids to the hormone-cytokine networks
responsible for embryo–uterine interactions, and this might represent a useful
framework for the interpretation of novel interactions between progesterone,
leptin, cytokines, FSH and (endo)cannabinoids [7, 32, 41].
An interesting outcome of the reported findings is that quantitation of
FAAH protein in maternal lymphocytes might become a diagnostic marker of
spontaneous abortion, easy to measure in routine analyses. Peripheral lymphocytes
are easily isolated from blood samples and immunochemical tests for
FAAH could be run automatically, both important advantages for monitoring
gestation in a low-risk population at large.
Since defective FAAH correlates with pregnancy failure, of interest is also
the perspective that factors able to enhance FAAH activity might become useful
therapeutic tools for the management of spontaneous abortion. Enhancers
of promoter activity able to mimic the actions of Ikaros and STAT3, or lipid
activators of FAAH like that released by mouse blastocysts, might open the