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Pregnenolone | The Master Steroid Hormone

By Tyler Woodward

Pregnenolone | The Master Steroid Hormone


Pregnenolone, the master steroid hormone, is the gateway to the synthesis of all other steroid hormones in the body. If you have low testosterone or estrogen levels, pregnenolone is the first place to look...


What Is Pregnenolone:

What Is Pregnenolone

Pregnenolone (P5) is a type of steroid hormone is the precursor to all the other steroid hormones. Due to its role in steroid hormone synthesis it’s commonly referred to as a prohormone or the master steroid hormone. These hormones include: 

  • Corticosteroids including cortisol, cortisone, 
  • Mineralocorticoids including aldosterone, 
  • Androgen Precursors including DHEA, DHEAS, testosterone progesterone

According to Dr. Ray Peat, Pregnenolone is one of the hormones of youth also including progesterone and DHEA. In fact for many years pregnenolone was believed to be an “inert substance” because when given to young animals who already produced an abundance of pregnenolone it didn’t have any effect. It wasn’t until the 1940s that the various benefits of pregnenolone in reducing stress became known.

Although pregnenolone is a precursor to many of the “stress” hormones like cortisol it’s actually a potent cortisol antagonist, binding to the cortisol receptor and thereby preventing cortisol from exerting its effects.

Read More: How To Get Rid Of Estrogen

How Is Pregnenolone Formed?:

How Is Pregnenolone Formed


Pregnenolone, the master steroid hormone, is formed from the master steroid precursor cholesterol. The liver regulates cholesterol production based on the amount consumed in your diet. The more cholesterol consumed in your diet, the less cholesterol the liver produces and visa versa. 

Next, in order to enter the cell the active thyroid hormone T3 or triiodothyronine must be present. T3 facilities cholesterol being absorbed into the cell from the serum (blood) where it then moves into the mitochondria for steroidogenesis, the process of synthesizing steroids. 

Once the cholesterol has been transported into the mitochondria the breakdown products of retinol (Animal Vitamin A), the retinoic acids, are known to play a vital role in the role of steroidogenesis, but the exact mechanism is unknown. Both Pregnenolone & Progesterone leave the mitochondria after production and actually activate their own stimulus. For these reasons supplementing with these does not decrease the production of these hormones and can actually act to “jumpstart” the production of these hormones. 

Direct Actions Of Cholesterol:

Actions Of Pregnenolone


  • Pregnenolone Inhibits Cortisol - Pregnenolone acts as a ACTH (adrenocorticotropic hormone) antagonist, meaning it fills the ACTH hormone receptor in place of ACTH hormones like cortisol. This prevents the ACTH hormones from exerting their effects which helps to promote glucose oxidation and reduce inflammation.
  • Pregnenolone Acts As An Endotoxin Antagonist - Endotoxin is an inflammatory molecule that is released from the “bad” bacteria in our gut and can leak through the gut lining into the bloodstream. When this happens it binds to the TLR4 receptor causing the release of inflammatory cytokines. Pregnenolone potently binds to these receptors preventing the release of these inflammatory cytokines (1, 2, 3).

Read More: The Top 25 Foods To Boost Testosterone Naturally

Benefits Of Pregnenolone:

Benefits Of Pregnenolone

  • Pregnenolone is potently anti-inflammatory †
  • Pregnenolone reduces stress †
  • May be useful in preventing osteoporosis
  • Has been used to increase memory and cognition in mice †
  • May be a possible treatment in manic depression (1, 2) and schizophrenia (1, 2) †
  • Pregnenolone helps to increase the levels of the other steroid hormones like DHEA and progesterone, but not cortisol. †

Dosing & Adverse Effects Of Pregnenolone:

Dosing & Side Effects Of Pregnenolone

There is not a lot of research on supplemental pregnenolone and it’s intended dosing or potential adverse effects. It’s theorized that it may cause side effects associated with other steroids including:

Because pregnenolone is the first hormone in the steroid hormone synthesis pathway compared to hormones like DHEA, testosterone or estrogen these effects are much more likely to be minimized. This is because pregnenolone has so many routes that it can take being converted into any of the steroid hormones. 

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