# Steroidogenesis

Category: Metabolism

Creation of steroids, usually referring to the conversion of cholesterol to hormones.

11 passages · 3 authors · 1993–2023 · Most-cited: [Georgi Dinkov](https://bioenergeticoracle.com/md/voices/georgi-dinkov/index.md)

Canonical page: https://bioenergeticoracle.com/concepts/steroidogenesis

## Synthesis

**Pregnenolone** is the foundational steroid hormone, synthesized from cholesterol within the mitochondria, and its production is the critical first step in all steroidogenesis. [Source 1, 4] This conversion is fundamentally dependent on **thyroid hormone** and **vitamin A**, and requires the structural integrity of the mitochondria, which is supported by factors like coconut oil, progesterone, and the limitation of lipid peroxidation. [Source 4] Without properly functional mitochondria, cholesterol cannot be converted to pregnenolone and will instead accumulate, making elevated cholesterol a reliable diagnostic indicator of hypothyroidism. [Source 1, 4] The process is also energetically demanding; the cell must be in a state of *proper oxidative metabolism*, as the synthesis of steroids pushes metabolism toward oxidative phosphorylation and away from glycolysis. [Source 1]

From pregnenolone, tissue-specific enzymes in the cytoplasm direct its conversion into either **progesterone** or **DHEA**, which then serve as precursors for the other specialized steroid hormones. [Source 4, 8] Peat argued that progesterone possesses a remarkable biological generality, acting not only as a precursor but also intrinsically exhibiting a wide range of protective functions, including lysosome stabilization, anti-estrogenic activity, and the promotion of thymus gland enlargement. [Source 2] Unlike the "terminal" steroids such as cortisol, estrogen, and aldosterone, which can have toxic effects in excess, Peat considered cholesterol, pregnenolone, and progesterone to be safe, and noted that taking progesterone or pregnenolone does not suppress the body's own synthesis, but can instead restore it. [Source 3, 8] Dinkov has written that the primary factors influencing steroid metabolism are vitamin A, LDL cholesterol, active thyroid hormone, and **NAD**, a product of oxidative phosphorylation. [Source 1]

The regulation of steroidogenesis is heavily influenced by the balance of opposing hormones. Estrogen, cortisol, and prolactin act as primary suppressors of proper gonadal function and steroid synthesis, creating vicious cycles where, for example, estrogen promotes cortisol synthesis and cortisol promotes aromatase activity. [Source 7] Dinkov has explained that interventions which are anti-estrogen, anti-cortisol, and pro-dopamine can each independently restore steroidogenesis, and that combining these mechanisms, such as through aromatase inhibition and MAO-B inhibition, may have synergistic effects. [Source 7] Peat emphasized that the conversion of cholesterol into protective hormones occurs in proportion to thyroid function, and that cholesterol is bound inside tissues as a defense against *PUFA toxicity*. [Source 3] Dinkov further noted that applying thyroid hormone to the gonads should stimulate steroidogenesis, provided there is sufficient raw material like cholesterol and cofactors like NADPH available. [Source 6]

The systemic availability of precursors is crucial for maintaining a balanced steroid profile. Peat observed that consuming progesterone or pregnenolone in food allows the body to produce an appropriate and balanced amount of all other steroid hormones, distinguishing natural steroids from synthetic progestins which inhibit metabolism. [Source 2] Dinkov has written that low cholesterol negatively affects steroidogenesis, and that stimulating local cellular metabolism without available cholesterol can cause a stress reaction, correlating with issues like hair loss. [Source 5] To ensure a broad precursor supply, Dinkov recommended that when taking a substance that might disrupt steroidogenesis, such as the cortisol blocker RU486, it should be accompanied by **pregnenolone** or progesterone to prevent downstream deficiencies. [Source 9] He also noted that fat-soluble vitamins A and D have non-overlapping but synergistic effects with anti-estrogenic steroids, and are required for proper steroidogenesis and metabolism. [Source 10]

The energetic state of the cell is the ultimate determinant of steroidogenic capacity. Dinkov has stated that **ATP levels** are the single most important factor for the first step of steroidogenesis, acting as a required co-factor for the StAR protein that transports cholesterol into the mitochondria. [Source 11] Peat's framework positions the entire steroidogenic cascade as an expression of *generative energy*, with the protective, youth-associated steroids like pregnenolone and progesterone being produced abundantly when oxidative metabolism is high, in contrast to the stress-driven production of terminal steroids like cortisol. [Source 4, 8] The appearance of cholesterol precursors like squalene in the skin or isoprene in the breath can indicate a block in this energy-dependent synthetic process. [Source 3, 4]

## People also ask

### How does thyroid function affect cholesterol conversion into hormones?

Peat argued that the conversion of cholesterol into protective hormones like pregnenolone occurs in proportion to thyroid function, and that without it, cholesterol accumulates as a sign of hypothyroidism.

### Why might taking progesterone not suppress the body's own hormone production?

Peat considered progesterone a safe precursor that, unlike terminal steroids such as cortisol, does not suppress endogenous synthesis but can help restore the body's natural steroidogenic capacity.

### What cellular condition is most critical for the first step of steroidogenesis?

Dinkov stated that ATP levels are the single most important factor, as ATP is a required co-factor for the StAR protein that transports cholesterol into the mitochondria.

## Related concepts

- [Fertility and Infertility](https://bioenergeticoracle.com/md/concepts/fertility-and-infertility/index.md)
- [Pituitary Gland](https://bioenergeticoracle.com/md/concepts/pituitary-gland/index.md)
- [Pregnenolone](https://bioenergeticoracle.com/md/concepts/pregnenolone/index.md)
- [Acne](https://bioenergeticoracle.com/md/concepts/acne/index.md)
- [Aging](https://bioenergeticoracle.com/md/concepts/aging/index.md)
- [Albumin](https://bioenergeticoracle.com/md/concepts/albumin/index.md)

## Cited passages

Passage numbers match the `[Source N]` markers in the synthesis above.

### Source 1 — The Youth Steroids: Pregnenolone, Progesterone & DHEA [Generative Energy #8]

Danny Roddy · Interview · Oct 8, 2015 · https://www.youtube.com/watch?v=sXkxViFxk9A

> **Danny Roddy:** Vitamin A, LDL cholesterol, active thyroid hormone, and then you said NAD, which is a product of oxidative phosphorylation or oxidative metabolism.
>
> **Georgi Dinkov:** That's correct. These are, in my opinion, these are the four main factors that influence steroid metabolism.
>
> **Danny Roddy:** And then that once again brings the importance of mitochondrial health because these steroids are produced in the mitochondria. And as you mentioned, if the mitochondria is damaged, they can't be produced.

### Source 2 — From PMS to Menopause: Female Hormones in Context

Ray Peat · Book · 1997

> **Ray Peat:** Pregnenolone (produced from cholesterol in the mitochondria), which is the precursor to progesterone and other steroids, has been used successfully to restore fertility (sperm count and motility, and, according to the wives--libido) in men. All of the natural steroids have functions that overlap to some extent--e.g., testosterone has some progestational function--but progesterone's generality is the most remarkable. 2. Steroid precursor function. The second aspect of progesterone's biological generality, besides its intrinsic hormonal activity, is its role as precursor for all of the other steroid hormones (see chart). When consumed in food (e.g., butter, brains, milk, ovaries--some cultures eat pork ovaries, many eat sea-urchin ovaries), it, like cholesterol, only more efficiently, enters the cycle of steroid synthesis near the beginning, so that it is a raw material, allowing normal amounts of the other hormones to be produced. This aspect of progesterone distinguishes it most strongly from the other progestins (e.g., medroxyprogesterone), which have had atoms introduced at unusual positions to inhibit metabolism and prolong activity (as well as to create a patentable and thus highly profitable substance). When we eat protein, we support the production of all the peptide hormones; likewise, natural progesterone (and pregnenolone, which is also found in brains, endocrine glands, and probably skin) serves to allow the body to produce an appropriate and balanced amount of all the other steroid hormones. 3. Anti-estrogen functions. A third aspect of progesterone's generality is a little less clear than its intrinsic generality and its function as a general steroid precursor, because this third form has to do with its overall antagonism to estrogen, and gains significance only to the extent that we see estrogen as having a very broad physiological role--for males as well as for females.

### Source 3 — Ray Peat Email Advice Depository — Post 675

Ray Peat · Email · Jun 17, 2021

> **Ray Peat:** No, I said the opposite, that the final steroids, especially cortisol, estrogen, and aldosterone can have toxic harmful effects, and that cholesterol, pregnenolone, and progesterone are safe. Squalene is very susceptible to oxidation, e.g., blackheads. The claims of the cosmetic industry are just as likely to be false as those of the drug industry. [references]
>
> **Question:** That is what I was saying you're saying as well Mr Peat however isn't DHT and even testosterone part of the end point steroids? pregnenolone turns to progesterone or dhea and progesterone can turn into cortisol or aldosterone while dhea can turn to testosterone which can turn to estrogen or DHT? in a stressed organism it is more likely pregnenolone will go towards cortisol and estrogen?
>
> **Ray Peat:** No, it just doesn’t work that way. “Can turn into" has nothing to do with how the organism works. It’s best to assume that everything on the internet is wrong—they are repeated thousands of times, on “reputable” sites, but it isn’t possible to learn anything useful by studying the great trash heap of the internet.

### Source 4 — Nutrition for Women

Ray Peat · Book · 1993

> The charts on the following pages show some of the factors involved in the formation of pregnenolone.
>
> Structural integrity of the mitochondria is essential for functional respiration and steroid synthesis. Coconut oil, thyroid hormone, pregnenolone, and progesterone stabilize mitochondrial structure.
>
> ISOPRENE (Precursor, shows up in nocturnal breath, probably indicating interference with its use.) CHOLESTEROL (Vitamin A, thyroid, and mitochondria integrity, which depend on factors that limit lipid peroxidation, are needed for its conversion into pregnenolone.) PREGNENOLONE (Formed in mitochondria, probably exits from that structure by a solubility gradient as well as specific mechanisms, to the cytoplasm, where tissue-specific enzymes in microsomes oxidize it further to either:) DHEA or PROGESTERONE (These and pregnenolone should be abundant, probably saturating cells to the solubility limit) ESTROGEN, TESTOSTERONE, CORTISOL, AND ALDOSTERONE (These are the "terminal" steroids, which vary greatly according to circumstances; in excess they are toxic, and in the absence of saturating amounts of the precursor steroids--which are slightly antagonistic "buffers"--even normal amounts can have exaggerated effects.)
>
> The accumulation of cholesterol clearly indicates the failure to convert it to steroids, so elevated cholesterol is a fairly reliable diagnostic indicator of hypothyroidism. The appearance of isoprene in some people's breath during the night is probably an indicator of something interfering with the synthesis of cholesterol. Highly allergic people often have extremely low cholesterol, making it impossible for them to synthesize normal amounts of the protective steroids.

### Source 5 — IdeaLabs Forum Q&A — SolBan

Georgi Dinkov · Forum Q&A · Feb 6, 2015

> **Georgi Dinkov:** (2017-01-12) Well, with low cholesterol steroidogenesis will be negatively affected. If the local metabolism of the cell is stimulated by SolBan and there is no cholesterol available this can cause a stress reaction. Low cholesterol also correlates with hair loss.
>
> **Rtm320:** (2017-01-11) Wondering how one would recommend applying it? I am currently using it on my scalp--as soon as I finish showering I part my wet hair working my way from one side to the other in about 1 inch segments spraying twice to cover all thinning areas. Do you think applying to wet hair might dilute it? I really want this to work in my daily routine. I was surprised and pleased it doesnt leave my hair feeling crispy--I blow dry my hair and it feel normal. I am so hesitant to say but I do believe it is helping to regrow hair in my temple region. Full disclosure I have been using my red light consistently as well but perhaps the two together is making the difference. Either way I am crossing my fingers and hope to continue with progress...
>
> **Georgi Dinkov:** (2017-01-12) SolBan is supposed to be applied on skin. People applying it on head usually have hair loss issues and apply it to the bald spots. Not sure why you would be applying it to hair, but if hair is wet it could dilute it. So, I would try to do it on dry hair at least.

### Source 6 — IdeaLabs Forum Q&A — TyroMix

Georgi Dinkov · Forum Q&A · Aug 5, 2016

> **Georgi Dinkov:** (2016-11-21) Just out of curiosity, how much do they charge for shipping to NZ?
>
> **Gl;itch.e:** (2016-11-21) Both places (purebulk, nutrabio) I was looking at around $21-22 shipping for 300 capsules worth of caffeine.
>
> **Georgi Dinkov:** (2016-11-21) Wow, that is expensive. The 300 capsules probably weight less than 6oz, so the actual USPS cost is about $13.
>
> **DaveFoster:** (2016-11-30) @haidut I have some TyroMix on hand, and I have a few questions: 1. I'd like to dilute TyroMix to the 1 mcg per drop concentration to start with this during the winter (as Peat's recommendation.) Do you know the approximate volume of the liquid? 2. Would applying this to the tests trigger steroidogenesis? 3. Is TyroMix okay to refrigerate, or will the product precipitate or become damaged?
>
> **Georgi Dinkov:** (2016-12-02) Applying thyroid to the gonads should stimulate steroidogenesis if there is enough raw material in the blood (cholesterol, pregnenolone, DHEA) and enough cofactors like NAD and NADPH (so niacinamide supplement may help).
>
> **A.R:** (2016-12-02) I have been testing this product on my subject for almost 2 weeks now. We have come to the conclusion that 1 drop daily is enough, as anything more gives head/temple pains. Positive effects so far have definitely been noticed, especially with digestion of food! No longer food just sits in the stomach killing the appetite, and constipation has improved aswell. Also, my subjects head hair seem to be shining, and dandruff has vanished, it's like the subject has oil in their hair! Negatives are, instead of being energetic after 1 drop, my subject must sleep. @haidut and anyone else with knowledge, is there any particular reason taking Thyroid would make my subject sleepy? And could you please suggest anything to help, as I need to get my subject being more active rather than just eating, pooping and sleeping. Thank you

### Source 7 — Gonadin(+) — IdeaLabs Cosmetic Ingredient

Georgi Dinkov · Product · Feb 17, 2017 · https://idealabs.ecwid.com/Gonadin-p79973225

> One of the most extensively studied methods of restoring steroidogenesis in gonads (both female and male) is through inhibition of the enzyme aromatase (i.e. decrease estrogen synthesis). Aromatase inhibitors are now commonly used not only for breast and other endocrine cancers, but for treating so-called secondary hypogonadism - i.e. estrogen, which only rises with age, appears to be one of the primary blockers of proper gonadal function. Estrogen receptor antagonists are also commonly used for such purposes, which confirms the negative role estrogen has on proper gonadal function.
>
> [references]
>
> In addition, other studies have demonstrated in both humans and animals that lowering prolactin and/or raising dopamine levels also has beneficial effects on gonadal function. It is now common to treat both male and female sexual dysfunction with dopamine agonists like bromocriptine, and the studies that also examined changes in steroid balance noticed normalization of gonadal function concurrent with the improvement in sexual function. This is not surprising as anti-prolactin/pro-dopamine chemicals tend to reduce estrogen synthesis and thus their overall effects are (functionally) similar to those or aromatase inhibitors. As a side note, it is not just dopamine agonists that have these beneficial effects on gonadal function, but any also any other intervention that results in increase in dopamine synthesis, decrease in its degradation (e.g. MAO-B inhibition), inhibition of its uptake, etc.
>
> [references]
>
> Furthermore, more recent studies have discovered that elevated cortisol also plays a direct role in suppressing gonadal function, and that role is independent of, but synergistic with, estrogen. In addition, cortisol is well-known to promote aromatase activity, while estrogen promotes cortisol synthesis, resulting in a positive feedback loop (a vicious circle is a more appropriate term, IMO) that can wreak havoc on gonadal function. Conversely, lowering cortisol (and/or blocking its effects at the receptor level), may also help restore proper steroidogenesis, even in aged/stressed organisms.
>
> [references]
>
> In summary, multiple studies demonstrate that anti-estrogen, anti-cortisol, and pro-dopamine pathways each have an independent beneficial effect on gonadal function and steroid balance. Also, a number of studies have suggested that a combination of these mechanisms may have synergistic effects stronger than each one on its own.

### Source 8 — Generative Energy: Restoring the Wholeness of Life

Ray Peat · Book · 1994

> Unfortunately. commercial milk animals are fed large amounts of grain, the oils of which act in opposition to the short and medium chain fats. Some tropical fruits and coconut oil provide some of these efficient and protective energy sources. As little as one or two teaspoonfuls of coconut oil per day appears to have a strong protective effect against obesity and cancer.
>
> ### Chapter 8: Steroids
>
> This type of molecule might be the most common carbon compound in the universe. It is made by single celled organisms, by plants, and by animals, and has many kinds of function. The steroid hormones are involved in all aspects of animal physiology, and overlap with control functions of the nervous system, peptide hormones, metabolites, prostaglandins, cyclic nucleotides, etc. Sometimes people speak of "steroids" when they mean glucocorticoids such as cortisol or a synthetic like dexamethasone, or, among athletes, when they mean anabolic steroids or synthetic androgens; and so it is common to associate "steroids" with harmful side effects. All foods contain steroids and sterols (a major type, containing an alcohol group and a side-chain) some of which are beneficial and some of which are toxic or allergenic. In animals, cholesterol is the basic sterol molecule, which is massively converted into other substances, including the steroid hormones. Thyroid hormone and vitamin A are required for this conversion. The first step occurs in the energyproducing mitochondrion, where cholesterol loses its sidechain and is slightly oxidized. producing pregnenolone. Being less fat soluble than cholesterol, pregnenolone leaves the mitochondrion, so it can't inhibit its own synthesis. Rather, it seems to stimulate its own synthesis, though this isn't as clearly established as in the case of progesterone. Depending on the tissue, pregnenolone will be converted by enzymes in the cytoplasm into either progesterone or DHEA
>
> (dehydroepiandrosterone). The fact that progesterone (and probably pregnenolone) stimulates its own synthesis means that taking it does not suppress the body's ability to synthesize it, as happens with cortisol. Sometimes, one dose or a few doses can restore the body's ability to produce enough of its own.

### Source 9 — Crucial Facts About Your Metabolism - Discussion Between Georgi Dinkov & Dr. Mercola

Georgi Dinkov · Interview · Sep 17, 2023

> **Dr. Joseph Mercola:** But you would want to take it with at least pregnenolone, right? Definitely, yeah.
>
> **Georgi Dinkov:** Because like any other steroid, it's probably going to disrupt one or more of the steps of the steroidal, the downstream cascade. And usually, even for the anabolic steroids, there's the infamous Roid Rage. And they found out that the reason the Roy rage occurs is that most anabolic steroids block the synthesis of progesterone as subsequently of a metabolite of progesterone known as allopregnanolone, which has a very potent calming and antidepressant effect. FDA recently approved allopregnanolone as a rapidly acting antidepressant. So clearly, if you're interfering with its production, you expect people to get either depressed or angry, which is a very common sign of depression as well. So these anabolic steroids were disrupting one or more of these steps. So taking pregnenolone or progesterone was found in animal studies to prevent the aggression associated with anabolic steroids. So RE486, also a steroidal molecule, likely to disrupt probably the initial steps of the steroidogenesis. So yes, pregnenolone or progesterone or progesterone and DHA. But I think pregnenolone is probably the easiest thing, just one thing for people to remember to take.

### Source 10 — IdeaLabs Forum Q&A — 11-keto DHT

Georgi Dinkov · Forum Q&A · Jul 21, 2016

> **DennisX:** (2016-09-17) Given 11K-DHTs anti-estrogen , anti-prolactin effect is there any need for EstoBan for the same? If so what would EstoBan add?
>
> **Georgi Dinkov:** (2016-09-17) They act via different mechanism, and the don't let the name of EstroBan fool you - the fat-soluble vitamins have a lot of other systemic beneficial effects that 11-keto DHT does not provide. Steroidogenesis and proper metabolism depend on vitamins A and D being present and just taking 11-keto DHT won't give you that. Again, they have different, non-overlapping but highly synergistic effects.
>
> **mirc12354:** (2016-09-22) I was just wondering - is a longer half-life of 11-keto DHT vs. regular DHT neccessary better? Could it be like it is with vitamin K2 mk4 vs. mk7 where a shorter half-life could be considered a sign of tissues absorbing it faster and preferentialy?
>
> **Georgi Dinkov:** (2016-09-22) I am not saying it is better, just noting that it is longer so it needs to be dosed less frequently or in lower doses than regular DHT.
>
> **conhnore:** (2016-09-22) my rat's acquiring grandiose feelings about himself and things generally in dosing 1-2mg 3x/week it's a source of discomfort for him - he reports ruminating on sticking out in public, feeling like he's acquiring advantages relative to his peers at too rapid a pace

### Source 11 — IdeaLabs Forum Q&A — Gonadin

Georgi Dinkov · Forum Q&A · Feb 17, 2017

> **Georgi Dinkov:** (2018-10-26) At least in animal studies it has been shown that ingestion of cholesterol precursors does raise cholesterol and steroids. There even be pathways we don't yet know about that allow the cholesterol precursors to be directly converted into steroids in various tissues. It has been confirmed in higher animals like pigs, so there is no reason why it would not happen in humans too.
>
> **Douglas Ek:** (2018-11-02) @haidut Whats phentadecanoic acid and why? Sorry if its a stupid question.
>
> **Georgi Dinkov:** (2018-11-02) It was shown to potently increase ATP levels and ATP levels are the single most important factor for the first step of steroidogenesis. It is a require co-factor for StAR to work well. The effects of this acid are described in the main SolBan thread. If you search the forum for "pentadecanoic" other threads where this is discussed may pop up.
>
> **Anders86:** (2018-11-03) After skimming the WADA prohibited list 2019 I don`t see any of these ingredients listed, but could you @haidut confirm this for me? My knowledge is limited in all these chemical names and I would feel safer in my supplementation. https://www.wada-ama.org/sites/default/files/wada_2019_english_prohibited_list.pdf As of now it seems like Thyroid, Pregnenolone, Gonadin, Niacinamide, Glycine, Aspirin and Vitamins would be a safe and good choice for competing and health.

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