Since personal chemistry
was brought up in another thread, and we are trying to figure out all the variables of why products work and don't
for individuals, I thought I paste this article from the Lily of the Vally Pheromones thread in the women's forum
that was bumped up a couple of days ago (lots of articles)
Anyone with any ideas on how we can use this
information to help us get laid easier would be appreciated.
March 7, 2003— Howard Hughes Medical Institute
(HHMI)
researches and their colleagues have discovered that escort
molecules are required to usher pheromone
receptors to the
surface of sensory neurons where they are needed to translate chemical cues.
In an
interesting twist, the researchers found that the escort
molecules belong to a family of proteins, called the
major
histocompatibility complex (MHC), which plays an important role in the immune system. The researchers
speculate that in addition to being escort molecules, the MHC proteins might actively modulate an animal's response
to pheromones.
Modulation of pheromone activity might aid in the recognition of other animals.
The
studies in mice add “a novel and unexpected layer of
complexity to the process of pheromone detection,” the
researchers wrote in an article published in the March 7, 2003, issue of the journal Cell. The article was
published online on March 4, 2003. The findings also suggest that, similarly, escort molecules, although of a
different kind, may be important in smell and taste receptors.
HHMI investigators Catherine Dulac at Harvard
University and
Kirsten Fischer Lindahl at the University of Texas Southwestern Medical Center led the research
teams that collaborated on the studies.
The pheromone communication system, which is found in a wide range of
mammals, involves detection of chemical odorants released by animals. Detection of pheromones takes place in a
specialized structure, called the vomeronasal organ (VNO).
Although the VNO resides in the nasal cavity, the
pheromone
sensory system is distinct from the sense of smell, as are the
chemical receptors involved. In
animals possessing a pheromone sensory system — including mice, dogs, cats and elephants — the system governs a
range of genetically preprogrammed mating, social ranking, maternal, and territorial defense
behaviors.
According to Dulac, untangling the complexity of the pheromone system has been a daunting task for
researchers. “For example, if you compare the number of receptors, which ranges between two hundred and four
hundred, and the number of behaviors they trigger, which ranges up to a dozen, there is a huge discrepancy,” she
said. “So, you can either postulate that there are hundreds of behaviors not yet described, or more likely a given
behavior involves the activation of multiple receptors.”
To begin sorting out the functions of the multitude
of
pheromone receptors, Dulac and her colleagues decided to study a subpopulation of sensory neurons in the VNO.
The researchers knew they could distinguish neurons that expressed one family of receptors, called V2R, from another
family, called V1R, so they used a technique called “subtractive differential screening of single cell cDNA
libraries” to compare the genes that are switched on in neurons bearing the two different types of pheromone
receptor.
Their comparisons — as well as sequencing of the discovered
genes and searches of gene
databases — yielded evidence that two families of MHC genes called M1 and M10 were
preferentially activated in
these neurons, said Dulac. The finding was surprising because MHC proteins commonly function on the surface of
immune cells to present foreign proteins to the immune system to trigger destruction of invading pathogens. The M10
proteins found in the VNO were different in structure and obviously in function from other such
molecules.
Dulac's and Fischer Lindahl's research teams set out to explore the structure and function of
the M10 type of MHC proteins that the genes produced. Their studies revealed that the MHC genes were exclusively
expressed in the VNO and in no other tissue. And within the VNO, they were only expressed in V2R-positive VNO
neurons. The researchers observed that each type of V2R receptor apparently had a specific type of M10 protein
associated with it.
“So, we found that there is a population of neurons in which each neuron expresses only
one type of pheromone receptor gene,” said Dulac. “We also were able to show that these individual neurons express
only one type of M10 gene. This told us there was some type of logic in that association.”
Additional studies
showed that the M10 gene was activated only after birth, which suggested that M10 only functions in
pheromone
sensing in the adult animal. The researchers showed that the M10 proteins, like the pheromone receptor proteins,
were localized to the tips of neurons, called dendrites, where chemical reception takes place.
Their studies
showed that the M10 protein, as well as an “
accessory” molecule, beta2-microglobulin, that accompanies such M10
proteins, directly interacted with the pheromone receptor molecule. Finally, they found that the M10 protein and its
accessory molecule were necessary for the pheromone receptor to reach the surface of the neuron.
The
researchers also explored the effects of knocking out the
key M10 accessory molecule, beta2-microglobulin, in
mice. They found that the beta2-microglobulin-knockout male mice lacked V2R receptors in their VNOs and also failed
to exhibit the normal aggressive behavior toward other males.
According to Dulac, the scientists' findings
show that M10 plays a crucial escort role for pheromone receptors, but it might well have a modulatory role. “The
fact that the receptor needs M10 to go to the surface, doesn't prove it's the exclusive role of the protein,” she
said. “We do know that each time researchers have described an association between a particular receptor and another
molecule at the cell surface, it has always been the case that the specificity of the original receptor is being
modified. So, we have found new molecular players, if you will, in the game of pheromone detection.”
Dulac
said that the newly discovered MHC molecule involvement could have important implications for understanding the
pheromone system. “This association opens all sorts of possibilities for the mechanism of pheromone detection,
because we know the animal can modulate its behavior according to the sex of another animal, its genetic background
and the elements that make up the identity of an animal.”
The discovery of escort molecules in the pheromone
system
could have implications for understanding the molecular machinery involved in smell and taste, Dulac
said. Researchers
knew that in cell cultures, olfactory and taste receptors seemed to require additional
molecules to reach the surfaces of cells. That observation hints at the need for still-undiscovered escort molecules
for those receptors, as well as for the V1R-expressing class of pheromone receptors, she said.
