I just came across this passage in the Wikipedia article on Serotonin:

Quote:Recent studies in China have found that male mice lose their heterosexuality if bred without serotonin.[78] By taking away the tryptophan hydroxylase 2 gene, which is needed to produce serotonin, male mice were deprived of serotonin from birth. However, experts have warned against making links between serotonin and human sexuality, as sexual preference in mice is largely driven by odours; humans are far less affected by odour cues.[79] [80]

Humans probably aren't affected by those primitive odourous signals, amiright??

So this got me thinking, which odorous signals are those rats responding to? Serotonin metabolites? Well, I wonder if people might be responsive to these as well.

It looks like the main metabolite of serotonin is 5-hydroxyindoleacetic acid, but melatonin is another that is secreted in the urine. Both of those are nice simple, lightweight molecules (191 g/mol and 232 g/mol, respectively). Melatonin has the advantage of being readily available. It's got a short half-life, is neuroactive, and is mostly secreted at night, when people are known to do most of their mating -- could melatonin be a sex pheromone?

Another one I've got my eye on is glycine. This plentiful amino acid is an extremely tiny and lightweight molecule (75 g/mol) that also acts as a neurotransmitter, and is excreted in urine. Seems to be a GABA modulator.

If you look at the pathways that effect pulsatile secretion of gonadotropin releasing hormone (GnRH), which is directly effected by mammalian pheromones, I think you will see that the role of serotonin and other neurotransmitters involved in the response to pheromones is probably modulated by their effect on GnRH.

James V. Kohl
http://www.pheromones.com

(04-18-2011 8:46 PM)dbot Wrote:  I just came across this passage in the Wikipedia article on Serotonin:

Humans probably aren't affected by those primitive odourous signals, amiright??

So this got me thinking, which odorous signals are those rats responding to? Serotonin metabolites? Well, I wonder if people might be responsive to these as well.

It looks like the main metabolite of serotonin is 5-hydroxyindoleacetic acid, but melatonin is another that is secreted in the urine. Both of those are nice simple, lightweight molecules (191 g/mol and 232 g/mol, respectively). Melatonin has the advantage of being readily available. It's got a short half-life, is neuroactive, and is mostly secreted at night, when people are known to do most of their mating -- could melatonin be a sex pheromone?

Another one I've got my eye on is glycine. This plentiful amino acid is an extremely tiny and lightweight molecule (75 g/mol) that also acts as a neurotransmitter, and is excreted in urine. Seems to be a GABA modulator.

Interesting, James. Here's an abstract about the effects of serotonin on GnRH:

Quote:Serotonin stimulates GnRH secretion through the c-Src-PLC 1 pathway in GT1–7 hypothalamic cells

Serotonin is a neurotransmitter that alters the hypothalamic-pituitary-adrenal axis. To date, however, the molecular mechanisms underlying the role of serotonin in hormone secretion have remained largely unclear. In this study, we report that serotonin activates phospholipase C (PLC) 1 in an Src-dependent manner in hypothalamic GT1–7 cells, and that pretreatment with either 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazole [3, 4-d] pyrimidine, an Src-kinase inhibitor, or U73122 [GenBank] , a PLC inhibitor, attenuates the serotonin-induced increase in calcium levels. Also, PLC 1 binds to c-Src through the Src-homology (SH) 223 domain upon serotonin treatment. Moreover, calcium increase is alleviated in the cells transientlyexpressing SH223 domain-deleted PLC 1 or lipase inactive mutant PLC 1, as compared with cells transfected with wild-type PLC 1. Furthermore, the inhibition of the activities of either PLC or Src results in a significant diminution of the serotonin-induced release of gonadotropin-releasing hormone (GnRH). In addition, the results of our small-interfering RNA experiment confirm that endogenous PLC 1 is a prerequisite for serotonin-mediated signaling pathways. Taken together, our findings demonstrate that serotonin stimulates the release of GnRH through the Src-PLC 1 pathway, via the modulation of intracellular calcium levels.

So serotonin stimulates the release of GnRH. And you're saying pheromones (probably androsterone and androstenol?) stimulate GnRH as well? If I'm reading it right then I think you're saying that the effect chain goes:

pheromones -> neurotransmitter modulation -> GnRH modulation

Is that right?

I still want melatonin to be a sex pheromone. I'm going to mix up a sprayer of some soon and see if it induces a tendency toward mating (or sleeping, or anything else for that matter)

(04-20-2011 6:32 PM)dbot Wrote:  So serotonin stimulates the release of GnRH. And you're saying pheromones (probably androsterone and androstenol?) stimulate GnRH as well? If I'm reading it right then I think you're saying that the effect chain goes:

pheromones -> neurotransmitter modulation -> GnRH modulation

Is that right?

Yes, but it's much more complex as there may be direct effects of androstenol on genes in GnRH-secreting neurons, or on a fraction of the GnRH molecule that acts directly as a neurotransmitter. The direct effect might then be associated with the indirect effect of an associated chemical like androsterone. Once the indirect effect is conditioned to occur, the androstenol might not be required to elicit the response.

(04-20-2011 6:32 PM)dbot Wrote:  I still want melatonin to be a sex pheromone. I'm going to mix up a sprayer of some soon and see if it induces a tendency toward mating (or sleeping, or anything else for that matter)

Different people want different hormones and metabolites to be sex pheromones. So far as is known, the effect on hormones comes through the GnRH neuronal system, which links hormones to behavior. Even if you link something like melatonin to changes in physiology, it can't be called a human pheromone until you show it effects the hormones that affect whatever behavior you claim is affected. That's why many people want to re-define the term pheromones, and make it fit what they can show (claim: oxytocin is a bonding pheromone), or say that it doesn't fit anything that's been shown (claim: there are no mammalian pheromones), or offer another term for use in subsets of species (vassana, signature scent, vomeropherin, et al.,) as opposed to modeling pheromone-driven behavior across species via species-specific molecular biology (Kohl, 2007). Then you still have the problem with using supraphysiological amounts of a chemical like melatonin, when exposure to it in social circumstances (if any) would never come close to the levels you are delivering in a spray.

James V. Kohl
http://www.pheromones.com