question: pheromone biosynthesis pathways

Pheromone Science Pheromone Theory & Molecules
1

Warning: Newbie questions here.

I’m wondering if there is available a diagram that maps out how the body synthesizes various pheromones. Specifically, something that shows things like “testosterone breaks down in the body into this, and this is excreted onto the skin, where this bacteria changes it into this”, etc… I’m interested in this for two reasons.

First, it might give clues as to why certain pheromones have certain effects. For example, a pheromone that is produced by a process that is more active in females when they are most fertile might make a male aroused, as women are only fertile for a few days a month and it is to the male’s advantage to have sex with a fertile female now, rather than to wait a few days. And so forth.

Second, it might help in the formulation of pheromone mixes. For example, if pheromone B is only produced from pheromone A on the skin, by bacteria, don’t they both give pretty much the same information about the biochemistry of the producer? Unless information about the producer’s skin bacteria count is valuable for some reason. If so, is there any reason to expect an altered effect from including both A and B in a mix? And if there is an altered effect in spite of this, why?

Hope this all makes sense.

T

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2

Here you go… a simplified version :slight_smile:

3

If you don’t have a scientific background this might help :slight_smile:

http://www.matteolongobardi.com/general_info/testosterone_clip_clip_image002_0000.gif

4

Did you put this together; it’s great! If it’s from someone else, I’d like to get a URL for the source, since I’ve never seen such a diagram in color. Also, do you know of anything that’s extended to show androsterone and etiocholanolone, or how we get to androstenol and androstenone? I think some people could benefit by seeing which metabolites are most likely to reflect circulating testosterone concentrations (e.g., as indicators of reproductive fitness.)

5

Oh, I’d love to take credit for it, but it’s not my design I’m afraid :roll_eyes: You can find it here;

LJ100 - Sexual Enhancement, Sports Nutrition, Anti-aging

Not the most scientifically robust source, but I do like the diagram. I’m an extremely visual learner so I always colourcode & highlight etc :slight_smile:

I don’t know if I have any of those in my folders, but I’ll have a look and see what I can find for you :slight_smile:

6

Here’s a brief diagram of Androstrone synthesis. It’s from one of my favourite sources :slight_smile: endotext.org. (I don’t know if it’s free access to the public or if it requires membership though)

http://www.endotext.org/adrenal/adrenal3/figures3/figure4.gif

Fig 4; Metabolism of adrenal androgens in the pilosebaceous unit (A) & adipocyte tissue (B).
Abbreviations: A, D4-androstenedione; T, testosterone; DHT, dihydrotestosterone; R, receptor; 3b-HSD, 3b-hydroxysteroid dehydrogenase; 17b-HSD, 17b-hydroxysteroid dehydrogenase; 5a-r, 5a-reductase; 3a-, 3b-diol, 3a-androstenediol, 3b-androstenediol; 3a-, 3b-diol-G, 3a-diol-glucuronide, 3b-diol-glucuronide; androsterone-G, androsterone glucorunide; ar, aromatase; E1, estrone; E2, estradiol-17b.

Active uptake of androgens and in situ estrogen synthesis occur in peripheral adipose tissue (Fig. 4B) through the enzymes 17b-HSD and aromatase, respectively. Peripheral conversion contributes significantly to circulating Testosterone levels in women, but not in men, in whom Testosterone is largely produced by the testis.

7

Here’s another one;

http://www.chemistry.uoguelph.ca/educmat/Chm452/gif/testoste.gif

Testosterone may be reduced to a more active form dihydrotestosterone locally at the actual site of action. Dihydrotestosterone is inactivated by conversion to androsterone among other inactive forms. Surplus androgens are disposed of by conjugation as sulfate esters or as glucuronide derivatives. These modifications increase the water solubility allowing for release in urine.

8

To re-address the original question about phero breakdown in the skin…

There’s a really good review article that summarizes things nicely;
Cutaneous Androgen Metabolism: Basic Research and Clinical Perspectives
Journal of Investigative Dermatology (2002) 119, 992–1007

"**The skin, especially the pilosebaceous unit composed of sebaceous glands and hair follicles, can synthesize androgens de novo from cholesterol or by locally converting circulating weaker androgens to more potent ones. As in other classical steroidogenic organs, the same six major enzyme systems are involved in cutaneous androgen metabolism, namely steroid sulfatase, 3 -hydroxy-steroid dehydrogenase, 17 -hydroxysteroid dehydrogenase, steroid 5 -reductase, 3 -hydroxysteroid dehydrogenase, and aromatase. **

**Sex hormones, like other steroid hormones, are synthesized from their major parental precursor cholesterol, which undergoes side chain cleavage by the mitochondrial P450 side chain cleavage enzyme (P450scc) to form 5-pregnenolone, releasing a C6 aldehyde.
5-pregnenolone, the required intermediate compound in the synthesis of all steroid hormones, can be converted intracellularly to progesterone by the action of 3 -ol-dehydrogenase to 4,5-isomerase or to 17 -hydroxypregnenolone by 17 -hydroxylase.

The ring system “sterane” of the steroid hormones, carrying a cyclopentanoperhydrophenanthrene nucleus, is a stable structure that cannot be broken down by mammalian cells. Conversion of active hormones to less active or inactive forms involves alteration of ring substituents rather than the ring structure itself.

Sex hormones can be easily distinguished by the carbon numbers, C-19 being androgens, C-18 being estrogens, and C-21 being progestenoids. Androgens are derivatives of androstane and contain either a keto group [e.g., dehydroepiandrosterone (DHEA) and androstenedione] or hydroxy group [testosterone and 5 -dihydrotestosterone (5 -DHT)] at position 17 of the ring system.

In classical “central” steroidogenic organs such as the gonads and the adrenal gland, testosterone can be derived mainly from two pathways: (i) progesterone, 17 -hydroxyprogesterone, 4-androstenedione, or (ii) 17 -hydroxypregnenolone, DHEA, 5-androstenediol. Alternatively, in many “peripheral” organs, such as the skin, the potent tissue androgen testosterone results from the conversion of circulating dehydroepiandrosterone sulfate (DHEA-S), a weak but most abundant androgen in higher primates, through the serial action of steroid sulfatase, 3 -hydro-xysteroid dehydrogenase/ 5-4 isomerase (3 - 5-HSD), and 17 -HSD. Testosterone can be further “activated” to the physiologically most potent tissue androgen 5 -DHT through the action of 5 -reductase or “inactivated” to estradiol by aromatase."

http://www.nature.com/jid/journal/v119/n5/images/5601659f1.gif

**

9

Given the higher primate specificity of DHEA/S production and its metabolism to androsterone (and etiocholanolone), I find it difficult to understand the focus on androstenone and androstenol as putative human pheromones. Have you seen anything that would support the conclusion that either androstenone or androstenol are signals of male reproductive fitness (e.g., somehow more directly related to circulating testosterone levels or masculinity as compared to androsterone)? Is there, for example, a similar chart that shows how gonadal testosterone is metabolized to androstenol and androstenone?

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

10

Most of my resources are medical rather than biochemical so there’s less info on androstenol & androstenone. I’ve got plenty of diagrams that show how androsterone, epi-androsterone & etiocholanolone are the main metabolites of androstenedione (and initially testosterone) but I don’t know the ratios.

As far as I know there are 4 pathways that testosterone can go down;

  • Inactivation
  • Diversification
  • Direct
  • Amplification
11

4 pathways that testosterone can go down;

  • Inactivation
  • Diversification
  • Direct
  • Amplification
12

Just to complicate things. Here’s the most complete diagram of androgen biosynthesis that I have…

Enjoy :wink:

You may not be able to see all the detail on the thumbnail but here’s the link;
http://dwb4.unl.edu/Chem/CHEM869K/CHEM869KLinks/www.genome.ad.jp/kegg/metabolism_links/map/map00150.html

13

Thanks, at least the diagram can be displayed and is readable on a single page, which makes it very useful. But, getting back to formulation, it’s interesting to see that androstenol and androstenone are missing. Androstenol is known to effect levels of luteinizing hormone in women, which makes it also likely to effect other hormone levels associated with sexual behavior. In contrast, I don’t think that anyone has ever looked at the effect of androstenone on hormones, which makes me wonder how product manufacturers think it affects behavior in any positive (or negative) manner. Admitedly, such things are over the top so far as most consumers are concerned. Still, it’s nice to know that someone else is paying attention to the underlying chemistry.

James V. Kohl

14

Another diagram :slight_smile: This one is from JVKohl himself :smiley:

Notes for the diagram;

The prenatal migration of GnRH neurosecretory neurons allow human pheromones to effect GnRH pulsatility, which modulates the concurrent maturation of the neuroendocrine, reproductive, and central nervous systems, thus influencing the development of human reproductive sexual behavior and other behavior.

AOS: accessory olfactory system; FSH: follicle stimulating hormone; GnRH: gonadotropin-releasing hormone; HPA: hypothalamic-pituitary-adrenal axis; HPG: hypothalamic-pituitary-gonadal axis; LH: luteinizing hormone; MOS: main olfactory system; VNO: vomeronasal organ.

15

Thanks, I wish the thumbnail could be expanded to a larger size, but may be able to address this when I update pheromones.com sometime in the next few weeks. The diagram is one that has changed little from its first presentation at the Society for the Scientific Study of Sexuality (SSSS) annual meeting in 1992. What has changed (I referred to it briefly during my 2007 SSSS plenary) is there is no longer support for the concept of a functional human VNO. That means that this model is the only mammalian model that directly links olfaction to hormones and behavior, and it extends well to humans because a functional VNO is not required. Marketers who continue to promote their products based on outdated VNO nonsense have captured the lion’s share of consumer dollars, and appear willing to continue doing so with their false claims. Hopefully, some day people will look beyond their product claims for scientific support. The science is there, it’s just been largely ignored.

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

16

this is excellent information and it is nice to have it in one place, I have these images and will be researching further.

Thanks so much.