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Cortisol: The Cortisol-Stress Connection & Pregnenolone Steel

Cortisol is a steroid hormone produced in the cortex of the adrenal glands. Cortisol assists you in regulating blood pressure, cardiovascular functions, and your body’s use of fats, proteins and carbohydrates. Cortisol is also involved in glucose metabolism, insulin release for blood sugar maintenance, and inflammatory response. Cortisol helps in responding to and coping with stress, trauma and environmental extremes. Normal levels of cortisol increases energy and metabolism and helps regulate blood pressure. Cortisol also enhances the integrity of blood vessels and reduces allergic and inflammatory responses.

Under normal circumstances, your body maintains or regulates your natural cortisol levels. Most healthy adults have a high cortisol level first thing in the morning and a low cortisol level at night. But when you’re feeling stressed, your body secretes more cortisol. Cortisol is frequently referred to as the “stress hormone” because it’s also secreted in higher levels during the body’s fight or flight response to stress. It is also responsible for several stress-related changes in your body.

Small increases of cortisol produce positive effects like improved memory, reduced sensitivity to pain, and increased sustained energy. However, elevated cortisol levels from prolonged or chronic stress can cause side effects such as suppression of thyroid function, cognitive impairment, increased blood pressure, decreased bone density, and blood sugar imbalances. High levels of cortisol can also lower your immunity and inflammatory responses, as well as slow down the wound healing process. [Cortisol and The Stress Connection. John R. Lee, M.D. and Virginia Hopkins Virginia Hopkins Health Watch, One-to-One Inc., 2009]

Chronic stress leads to chronically high levels of cortisol in your body. This creates a need for higher levels of other hormones (e.g. thyroid, insulin, estrogen and testosterone) in order to do the same job.

Chronic high concentration of cortisol is toxic to brain cells and can cause short-term memory loss. A lifetime of high cortisol levels may be a primary contributor to Alzheimer’s disease and senile dementia. High cortisol is also a primary cause of osteoporosis. Hormones play an intrinsic role in keeping skin healthy and vibrant. Our skin is teeming with hormone receptor sites and shows signs of aging very quickly.

These changes apply to both men and women all over the body - not just the face. Menopausal decline in Oestrogen levels contributes to deterioration in skin health in a number of ways, including wrinkling, dryness, thinning and reduced collagen content. Men with low testosterone also have thinning skin and show signs of aging quickly.

Stress has a hormonal impact on skin vitality as well. Also lifestyle factors like sleep, stress, diet and skincare products can affect your skin quality.

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, increases blood sugar, and inhibits peristalsis (amongst 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 precursor 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.