3. Umbruch 4.4..2005 - Online Pot

Endocannabinoids and regulation of fertility 73
who miscarried compared to those who did not [30]. None of the other proteins
of the endocannabinoid system were affected (Tab. 1). In addition, we
found that the levels of AEA and FAAH in peripheral lymphocytes undergo
specific variations during the various phases of the human ovulatory cycle. In
particular, the highest levels of FAAH activity, paralleled by the lowest AEA
concentrations, were found on day 21 of gestation, which is the period that
temporally coincides with the putative window of implantation in humans
[31]. Instead PLD, AMT and CB 1 receptors of lymphocytes did not change
during the menstrual cycle (Tab. 2). This evidence strengthens the concept
that high FAAH activity and low AEA levels may be among the factors that
contribute to the success of implantation. Furthermore, they point towards a
key role of FAAH, but not of the other proteins of the endocannabinoid system,
in lymphocyte-mediated control of the hormone-cytokine networks at
the feto–maternal interface. In this line, recent studies have shown that progesterone
up-regulates FAAH, but not PLD, AMT or CB 1 receptors, in human
lymphocytes [32]. Some molecular details of this activity have been unravelled,
showing that progesterone, through formation of a complex with its
intracellular receptor, enhances the level of the trancription factor Ikaros,
which in turn enhances FAAH gene expression by binding to a specific
sequence in the promoter region [32]. Also leptin, the product of the obese
gene which controls fertility [33] and immune function [34], has been recently
shown to enhance FAAH gene transcription through a STAT3-mediated
activation of the FAAH promoter at a cAMP-response element (CRE)-like
site [32]. These findings suggest that the hydrolase can be regarded as a molecular
integrator of well-known fertility signals, and that it controls the activity
of AEA in reproduction.
Table 2. The endocannabinoid system in human ovulatory cycle. The endogenous levels of AEA, the
binding to CB 1 receptors, and the activity of PLD, FAAH and AMT, were assayed in peripheral lymphocytes
of healthy women at different stages of the menstrual cycle
Parameter Day 7 Day 14 Day 21
AEA content 2.15 ± 0.20 (100%) 3.76 ± 0.35 (175%) *
1.29 ± 0.14 (60%) *
(pmol/mg protein)
CB1 binding
(cpm/mg protein)
20000 ± 2030 (100%) 20000 ± 2050 (100%) 17400 ± 1795 (87%)
PLD activity
(pmol/min/mg protein)
130 ± 15 (100%) 117 ± 12 (90%) 130 ± 15 (100%)
FAAH activity
(pmol/min/mg protein)
115 ± 12 (100%) 46 ± 5 (40%) 253 ± 22 (220%)
AMT activity
(pmol/min/mg protein)
50 ± 5 (100%) 43 ± 4 (86%) 45 ± 5 (90%)
* P < 0.05 versus day 7 (P>0.05 in all other cases).
P < 0.01 versus day 7 (P>0.05 in all other cases).