Proposed Adaptive Values of the Endocannabinoid SystemBiology 342 Fall 06 |
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Adaptive ValueAdaptive Value - degree to which a characteristic benefits an organism by increasing its reproductive successReproductive
hormones Marijuana smoking
is
associated with the suppression of luetnizing hormone (LH)* secretion
and shortened luteal phase in women (Mendelson et al., 1986).
Marijuana smoking also causes reductions of LH and testosterone plasma
levels, leading to impotence and reduced sperm count in men (Kolodny et
al., 1974). Female and male genital tract fluids contain
significant concentrations of endocannabinoids (Schuel et al.,
2002a). Smoking marijuana thus suppresses the mechanisms for
regulating the hypothalamic- pituitary- gonad axis. The
presence
of endocannabinoids and cannabinoid receptors suggest an important role
for endocannabinoids in regulating the reproductive tract.
CB1
receptors are present in Leydig cells and involvemed in
testosterone secretion (Wenger et al., 2001).
* Luteinizing Hormone (LH) is
synthesized and
secreted by gonadotropes in the anterior lobe of the pituitary gland.
It is necessary for proper reproductive function. In females, an acute
rise of LH levels triggers ovulation. In the male, it stimulates leydig
cell production of testosterone
Endocannabinoids and Embryo Development/Implantation/Initiation of the Suckling Response
Endocannabinoid signalling via CB1 regulates cleavage of mouse eggs,
oviductal transport of preimplantation embryos, blastocyst hatching
from the zona pellucida, and implantation of blastocysts into the
uterine mucosa (Schuel, 2006). The expression of anandamide
in
the oviduct and uterus interacts with the developing embryo to ensure
maternal preparation is coordinated with preimplantation embryo
development and embryo implantation (Paria, 2002). Failure of
proper endocannabinoid signalling to occur results in ectopic
pregnancy, where the embryo remains in the fallopian tube (Wang, 2004).
The anandamide gradient is controlled by FAAH (fatty-acid
acyl
hydrogenase), which is responsible for breaking down the
endocannabinoid anandamide is formed from NAPE through a cleavage by
the enzyme phospholipase-D (PLD). The anandamide precursor
with
enzyme processor PLD is termed NAPE-PLD. The image below
demonstrates the gradient of FAAH to NAPE-PLD necessary for the embryo
to
survive. Interestingly, Low FAAH in circulating
maternal lymphocytes has been shown to be
an early (<8 weeks of gestation) predictor of spontaneous
abortion
in humans (Maccarrone and Finazzi-Agrò, 2004)
The endocannabinoid system is essential for the initiation of the suckling response in mice, as demonstrated by receptor blockades. If by day two the suckling response is not formed, the mouse will never developl the suckling response. This finding compliments both what we know of endocannabinoid's initiation of feeding and a baby-disease NOFTT, called Non-Organic Failure-to -Thrive, for up to now no reason for this disease had been found.
Diagram of a Spermatozoa From: http://en.wikipedia.org/wiki/Image:Simplified_spermatozoon_diagram.svg
Sperm and How they are like Neurons Sperm,
like neurons,
have functional cannabinoid receptors. Human sperm express CB1 (but not
CB2) in the head and middle section of the sperm. The activation of
this receptor by anandamide reduces sperm motility and inhibits
capacitation-induced acrosome reaction* (AR) (Rosato et al,
2005). Cannabinoids and endocannabinoids negatively influence
sperm functions. Cannabinoids inhibit fertilization in the
sea
urchin by reducing the fertilizing ability of sperm (Schuel et al.,
2002b). It is well known that marijuana smokers show an alteration in
fertility potential. This could be due at least in part to a negative
influence on the mechanisms regulating the
hypothalamic-pituitary-testicular axis, but also to a direct inhibitory
effect of cannabinoids on human sperm.
Sertoli cells (the cells that nurture sperm maturation in the testes) in mice have been shown to express a complete endocannabinoid system (Macarrone, et al., 2004). In mammals, ejaculated sperm is not automatically prepared to fertilize an egg. Once the sperm are in the female reproductive tract, they become ‘capactiated' by undergoing a series of maturational changes including changes on the head enabling it to bind to the zona pellucida** and changes in the tail of the sperm, giving them motility (Yanagimachi, 1994). The presence of AEA, its precurors, and its processing enzymes in boar sperm has been demonstrated (Macarrone et al., 2005). The authors present convincing evidence that the AEA present in both seminal plasma and uterine fluids functions to prevent premature capacitation in freshly ejaculated sperm through a mechanism regulated by the CB1 receptor. Sperm are exposed to progressively reduced concentrations of AEA in the proximal female genital tract (Schuel etl al., 2002b). By the time the sperm reach the oviduct, the sperm would be under capacitating conditions, with lowered AEA concentrations to allow for increased motility, metabolism, and the ability to fertilize the egg. Endocannabinoids have been shown to reduce sperm motility by reducing the mitochondrial energetic output in sperm (Rosatto et al., 2005). Furthermore, available data suggest that communication between eggs and sperm via AEA helps prevent polyspermy in animals ranging from sea urchins to humans by inhibiting sperm acrosomal release. Cannabinoids modulate acrosomal release in sperm through a mechanism seemingly identical to that by which they inhibit neurotransmitter release from neurons. For more information on how sperm are like neurons see the minireview a tale of two cells: Endocannabinoid-signaling regulates functions of Neurons andSperm (Schuel and Berckman, 2005). In summary, a conserved physiological role for the endocannabinoid inhibition of sperm motility appears well-supported (Cobellis et al., 2006). * The acrosome
reaction (AR) occurrs
when the sperm fuses with the zona pellucida, releasing digestive
enzymes to allow the genetic contents of the sperm to enter the egg's
cyptoplasm. ** The Zona Pellucida is a glycoprotein membrane surrounding the plasma membrane of an oocyte. This structure binds spermatozoa (sperm) and is required to initiate the acrosome reaction. The Authors' Behavioral Conjectures While a role for the endocannabinoid system in
successful
reproduction, one cannot help but postulate based on what we know.
If sex resulted in an increased concentration of
endocannabinoids, it would facilitate a (possibly addictive)
dopamine-reward response to sex similar to that involved in food,
alcohol, and opiate reward (all of which are modulated by the
endocannabinoid system). Also, it would have an anxiolytic
effect
that would keep a femal reclining and inactive while the sperm would
make their way toward an egg and away from the crucial area where they
might spill out of the female stands up. An increase in
endocannabinoids would facilitate a decrease in peripheral metabolism
and a reduction in motility. |