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HPA axis: what is pregnenolone steal?

April 23, 2012
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The human response to a stressful situation occurs in two places.  First, it occurs immediately in the sympathetic nervous system.  This increases heart rate, increases breathing rate, initiates sweating, dilates pupils, jacks up blood sugar, and inhibits peristalsis.  Among other things.

Secondly, this amped up signal is relayed to the endocrine system via the hypothalamus.     Immediately, the HPA axis gets adrenaline pumping out of the adrenal glands.  Secondarily, via CRH secretion to the pituitary, and ACTH secretion to the adrenals, cortisol is secreted into the bloodstream.  The secretion of cortisol is a fast action, but it is a bit slower than the first-up, lightning-fast reaction of the nervous system I described above.  It also endures for longer.  This is true especially if the stress doesn’t run it’s course quickly, for example, if you hate your job.  Cortisol has many of the same physiological effects as activating the sympathetic nervous system does, at least on the surface.  It spikes blood sugar, inhibits digestion, and, importantly, puts a halt to immune activities.

So how does the body so easily produce enough cortisol to flood the system like this in times of need?

It steals it!   It “steals” the common building block of adrenal hormones, pregnenolone, from it’s ordinary functions.  It diverts production down a specific cascade that leads to cortisol.  This enables lots of cortisol production, but it inhibits the production of just about everything else.

Cholesterol is the mother molecule of the endocrine system.   Mitochondria, controlled by the adrenals, convert cholesterol into pregnenolone.  From pregnenolone, virtually all of the rest of the hormones are produced.   From here, one of two things can happen:  the pregnenolone can be converted to progesterone or it can be converted to DHEA.  DHEA is the precurosor to all of the other sex hormones, at least those produced by the adrenal system.


This means that a stressful situation will steal all of the pregnenolone from its normal production of DHEA and shunt it into cortisol.   The body will prefer this pathway to the detriment of all other adrenal pathways.   Hormone production will suffer greatly.

You might object to how detrimental I’m making this sound because you understand that most of the sex hormones are produced in gonadal tissue.  This is correct.  However, there are a handful of complicating factors that make what could have been the reproductive system’s saving grace ultimately problematic.

First: non-dominant sex hormones (such as testosterone in a woman or estrogen in a man) are often produced in the adrenal glands at higher levels than in the gonads.  For example, the largest source of testosterone in the female body is the adrenal gland, even though a woman does produce small amounts of testosterone in her ovaries.   Secondly, the production of sex hormones in the adrenals is still important for the overall level of sex hormones in the body, particularly for achieving hormonal balance.  The adrenal glands are capable of immediately responding to hypothalamic signalling, such that when the hypothalamus gets a signal that a certain hormone is too high or too low in the bloodstream, the adrenals can make up for the difference.  And third, certainly yes, the pituitary still exists to send signals to the gonads.   But cortisol imposes negative feedback on the HPA axis.  Cortisol signals to the hypothalamus to downregulate signalling to the pituitary.  So with cortisol in the system, the production of hormones in gonadal tissue decreases, too. This is the primary long-term pathway by which stress inhibits reproductive function.

Pregnenolone steal, therefore, is at face value a simple phenomenon.  The body gets stressed, and it shunts hormone production into pathways that are meant to be helpful in times of need.    There are levels of complications beneath this action, but in the end it boils down to– as so much of my work does– the fact that stress inhibits reproduction on a variety of fronts.

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Managing director of Paleo for Women and author of Sexy by Nature.


  1. Pingback: My Quest for Primal Fire (or Health) - Page 58 | Mark's Daily Apple Health and Fitness Forum page 58

  2. Ah! Such a needed blog post. You answered a lot of questions that have been simmering in the back of my head as I do more of my own research. The explanation of hormones from adrendals v. gonads especially cleared up a few things up for me. And the last paragraph is just reiterating what’s been becoming more and more important – better management of stress. It seems so obvious that life without stress is better, but we usually think of its management as optional. It’s also harder to quantify than diet and exercise management, so it gets left behind. Anybody who has spent considerable time improving diet and exercise without all the results they want has to know there’s another big component to health missing.

    It’s a hard realization, but I’m slowly but surely taking sleep, meditation and enjoyable (not stressful) exercise seriously. Also … feel free to laugh, because I’m doing it anyway … I’m experimenting with no sexual stimulation for a while. That’s right, not only no sex, but no masturbation. I can because I’m single and I’m desperate enough to see if it helps. The more I researched adrenal fatigue, the more I realized that maybe I needed to forgo orgasm for a while maybe just to heal and let my hormones restore themselves. This article also further convinced me it could be a good idea: http://www.herballove.com/article.asp?art=552

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  4. Okay, so I recently found out through lots and lots of blood work that my cortisol levels are like 100 times what they should be. Enough the lab called my doc and said we have never seen such results. So more tests were done with same result and also apparently my body has stopped making any pregnenolone at all. Again, a call to the doc from the lab, results were less than a trace. More tests. So, among everything else I am starting iodine drops for auto immune thyroiditis and pregnenolone suupplement and Vitamin D among other things. Does this sound right to you? I am not good at taking pills, any pills, and yet I am up to eight a day and as soon as I get the nerve up, the iodine drops, too. I just want to know, does this sound right? Everything you wrote sounds familiar and answered some questions but I have so many. I just want to feel… normal? Not sure what that is but it is my goal. I cannot exercise due to painful arthritis, I am 53 and starting to shuffle. I don’t want to shuffle. It has been four weeks since I had any grain, ANY grain and cut so far down on sugar but that is actually harder for me than all the grains. Am I doing this right? Should I take the pregnenolone supplement, iodine drops and so forth? Eeeek and thank you for any info you can pass my way.

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  7. have you considered trying reiki? A complementary therapy that chanels energy to bring balance and deep deep relaxation. This will naturally help to reduce cortisol and therefore be likely to help bring other hormones levels back into balance. No side effects.. Worth a try don’t you think?

    Zen Reiki Cambridgeshire UK

    Zen Reiki

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  9. I am in stage 3 of adrenal fatigue. I want to start taking pregnenolone because nothing has worked for me so far. Is this the way to go? Any comments are greatly appreciated. Thanks

  10. hyperactivity with ADD

    What do you think:

    ive learned pituatory relates to our spirit. when i get hyper…talk too much…with adreniline pumping…i feel a high from the adrenaline..but then a disconect from my calm spirit is what im left with. it takes a good 20 min to get re attached to my spirit and feel more aware of others. more aware of the real moment. more attractive to my friends and co workers. i hate tge hyper me that happens. it starts out happy about a topic and then a sort of overload occurs and multiple thoughts dump in and im talking too much…fleeting thoughts. pissing people off.
    adenals block pitituatory which blocks my spiritual alignment. perhaps my answer is figure out nutrtional and behavioral things that stop the adrenals from firing so much. look forward to suggestions.
    challenge. i crave stimulants to help with ADD slow brain processing which is dopamine related. adderal improved my brain power but it can trigger adrenals.excuse type o…using droid

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