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Steroidogenic Pathway Part 1

The normal stress response begins with the stressor stimulating the hypothalamus in the brain. This then causes the adrenal cortex to secrete cortisol (the stress or catabolic hormone) and DHEA (the precursor to the sex hormones, or anabolic hormone). Remember that catabolic means to break down and anabolic to build up. You will see what I mean shortly. The steroidogenic pathways define the road map that the body uses to produce both stress and sex hormones. The path begins with cholesterol. It becomes evident that if cholesterol levels are low, either naturally or by treatment with medication, the body will not be able to sufficiently produce sex hormones and the stress response may eventually suffer! Functional medicine guidelines state that cholesterol levels below 150 are unacceptable for this reason. Several months ago, I wrote a local cardiologist about one of his patients with a treated cholesterol of 106! The patient could not produce sex hormones and his testosterone level was almost non-existent. The cardiologist was unaware of this phenomenon but refused to ease up on the patient’s treatment regimen. Unfortunately, this physician is one of many who has not kept up on the data on the interactions between cholesterol, heart disease and sex hormone production. I advised the patient to seek a second opinion.

Once cortisol production is ramped up due to the acute stressor, its actions become catabolic. Cortisol wants to get us to move, to flee or to fight! Increased cortisol maintains blood glucose levels during stress reactions so that additional glucose for energy is delivered to the brain, heart, lungs and skeletal muscle. Cortisol promotes liver protein synthesis and glucose formation but stimulates protein breakdown elsewhere in the body as a source of needed energy. Cortisol also stimulates the breakdown of glycogen, the storage form of glucose and at lease initially, stimulated the breakdown of fat for energy. Cortisol is also anti-inflammatory initially. Once the stressor is contained, cortisol sends a negative feedback signal to the hypothalamus to cease stimulation of the adrenal glands. Cortisol levels then return to normal.

The stimulation of the adrenal cortex in the early stages of the stress response also causes the production of DHEA, which is the pro hormone for the sex steroids. DHEA is truly the anti-aging hormone. It is anabolic in that it is immune supporting, anti-atherogenic, enhances insulin sensitivity, maintains tissue strength and repair, supports bone density, enhances memory and promotes a sense of well being.

As long as the body functions normally and the stress response is contained and acute, this scenario functions beautifully. However, when the stress response goes awry and becomes chronic, as it does 90+% of the time, the pathway is disrupted. Cortisol demands drive the DHEA anabolic reactions towards the production of cortisol and subsequently, DHEA reserves decrease. This leads to a decrease in all of the beneficial anabolic effects of DHEA including the production of sex hormones. As the demand for cortisol increases with a chronic stress response, DHEA is “stolen” from its normal functions to provide a substrate for cortisol production. This “cortisol steal syndrome” defines chronic stress. As we age, the resiliency of the stress response to regulate itself becomes less and less. We find that chronic stress increases the aging phenomenon and predisposes to many of the chronic diseases of aging. Once this chronicity goes on for a while, the brain shuts down the adrenal gland’s production of cortisol in order to “save” the body, and adrenal fatigue results. So if you have read the last three blogs, you know how the story can end. But, I am not through with the beginning just yet…

1 comment

  1. Dot says:

    Amazing info Dr G. Easy to understand easy to connect the DOTS!

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