Marty Sawaya, 3 beta HSD and androgenic alopecia (1988)

[michael barry]

Journal of Investigative Dermatology (1988) 91, 101–105; doi:10.1111/1523-1747.ep12463393

5-3-Hydroxysteroid Dehydrogenase Activity in Sebaceous Glands of Scalp in Male-Pattern Baldness
Marty E Sawaya, Lawrence S Honig, Larry D Garland and S L Hsia

Department of Dermatology and Cutaneous Surgery, University of Miami School of Medicine, Miami, Florida, U.S.A.

Received 17 February 1987; Accepted 1 December 1987.

Top of pageAbstract
Sebaceous glands were isolated by manual dissection using a stereomicroscope from skin specimens of bald scalp of men with male-pattern baldness undergoing hair transplant or scalp reduction surgery and also from specimens taken from hairy and bald areas of scalp at autopsy of adult male victims of accidental death within 3 h post mortem. Homogenates of the isolated glands exhibited activities of 5-3-hydroxysteroid dehydrogenase (3HSD), 17-hydroxysteroid dehydrogenase and testosterone 5-reductase by the conversion of [3H]dehydroepiandrosterone (DHA) to 3H-4-androstenedione (AD), [3H]testosterone, and [3H]dihydrotestosterone. Homogenates of glands from bald (B) scalp had greater 3HSD activity than homogenates of glands from hairy (H) scalp. After differential centrifugation, 3HSD activity was found mainly in the microsomal and 105,000 g supernatant fractions. Specific activity of the enzyme based on protein mass was highest in the microsomal fraction; however, the total 3HSD activity in the 105,000 g supernatent of Bald glands was significantly (p < .01) greater than that of Hairy glands. 3HSD activity in sebaceous glands isolated from autopsy specimens did not differ from that of glands isolated from surgical specimens in apparent Km(0.13- 0.14 M), pH optima (8.0), or coenzyme requirement for NAD. Since substantial 3HSD activity was present in the cytosol, and cytosol of Bald glands showed increased 3HSD activity, the increased conversion of DHA to Androstenidione may be a critical step for androgenic action and may be responsible for excessive androgenicity in male-pattern baldness.







Note....................I just posted that 3-beta HSD is apparently at least somewhat inhibited by mentha piperta (peppermint).

I find it also very interesting to note that people born with 3 beta HSD deficiency or 17 beta HSD deficiency also often suffer from pseudohermaphrodism (just like people born with alpha five reductase type two deficiency). http://emedicine.medscape.com/article/920621-overview

(and for the 17 beta HSD deficiency and pseudohermaphrodism, http://en.wikipedia.org/wiki/17-beta-hy ... deficiency)






Note: Ive read that alpha five reductase has two "co-factors" in its creation. 17 beta HSD and NADPH. Its been claimed that certain zinc-molecules (sulfites I think, but dont hold me to that) and coal tar can inhibit NADPH, and thus in an indirect way inhibit alpha five reductase. However NADPH is apparently helpful for cellular energy or metabolism or some such.......so one's hair might not grow as fast or the individual hairs might not be quite as robust if it was completely inhibited (interestingly the pyrithione zinc shampoo study showed about a 10% increase in anagen hairs, but something like a 2% decrease in hair diameter...........but a bit MORE sebum*, which is mystifying).



*irritants have been shown to increase sebum, so that might be a reason. Perhaps you sebacous glands find pyrithione zinc "irritating" ----LOL.




Anyway................there is a dog study with an ingredient that supposedly inhibits 3 beta HSD, called trilostane (http://ajpregu.physiology.org/cgi/conte ... 288/2/R389),
and it apparently can regrow hair on dogs that have lost their hair:

Case Report

The Use of Trilostane for the Treatment of Alopecia X in Alaskan Malamutes
F. Leone, DVM, R. Cerundolo, DVM, Diplomate ECVD, A. Vercelli, DVM and D.H. Lloyd, BVetMed, PhD, Diplomate ECVD
From the Clinica Veterinaria Adriatica (Leone), Senigallia, SS Adriatica Nord 50/1-2, 60019 Senigallia, Italy; The Department of Clinical Studies (Cerundolo), School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6010; Ambulatorio Veterinario Associato (Vercelli), Corso Traiano 99d, 10135 Torino, Italy; and the Department of Veterinary Clinical Sciences (Lloyd), Royal Veterinary College, University of London, North Mymms, Hatfield, Herts, AL9 7TA, England.

Address all correspondence to Dr. Cerundolo.


Three Alaskan malamutes with hair loss and slightly elevated blood concentrations of 17-hydroxyprogesterone after stimulation with adrenocorticotropic hormone (ACTH) were treated with trilostane. Trilostane, an inhibitor of 3 ß-hydroxysteroid dehydrogenase, was given twice daily at a dose of 3.0 to 3.6 mg/kg per day orally for 4 to 6 months. Routine ACTH stimulation tests were performed over 8 months to evaluate the degree of adrenal function suppression. Treatment with trilostane led to complete hair regrowth in all three dogs within 6 months. No adverse effects associated with trilostane were recognized.

Note: I found some trilostane dog shampoos.


The morale of this story................its better to be a dog with alopecia than a human with alopecia. LOL

 

[michael barry]

Id like to "add a reply" to my little post here by noting something Ive noted before theorizing about the genetics behind male pattern baldness.



This is what is on wikipedia about baldness genetics:

"
"gene studies in 2005 and 2007 stress the importance of the maternal line in the inheritance of male pattern baldness. German researchers name the androgen receptor gene as the cardinal prerequisite for balding[7]. They conclude that a certain variant of the androgen receptor is needed for Androgenetic Alopecia to develop. In the same year the results of this study were confirmed by other researchers [8]. This gene is recessive and a female would need two X chromosomes with the defect to show typical male pattern alopecia. Seeing that androgens and their interaction with the androgen receptor are the cause of Androgenetic Alopecia it seems logical that the androgen receptor gene plays an important part in its development.

Other research in 2007 suggests another gene on the X chromosome, that lies close to the androgen receptor gene, is an important gene in male pattern baldness. They found the region Xq11-q12 on the X-chromosome to be strongly associated with Androgenetic Alopecia in males. They point at the EDA2R gene as the gene that is mostly associated with Androgenetic Alopecia. This finding has been replicated in at least three follow independant studies.

Other genes involved with hair loss have been found. One of them being a gene on chromosome 3. The gene is located at 3q26[9]. This gene is also involved in a type of baldness associated with mental retardation. This gene is recessive .

Another gene that might be involved in hair loss is the P2RY5. This gene is linked to hair structure. Certain variants can lead to baldness at birth while another variant causes “wooly hairâ€￾.

Recent research confirmed the X linked androgen receptor as the most important gene(see the picture underneath). With a gene on chromosome 20 being the second most important determinant gene (snpedia)

In May 2009, researchers in Japan identified a gene, Sox21, that appears to be responsible for hair loss in people.[1]

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As Ive brought up in the past, a German study with something north of 5,000 men was conducted a few years ago that looked for the genetic differences between balding men and hirsuite men. It was found that 98.6% of balding men had the same type of androgen receptor gene.

However, 76% of the hirsute men (guys who kept most of their hair), had the same kind of androgen-receptor gene. It was theorized that the balding guys might have more CAG-repeat mutations on their androgen-receptor gene.


But the study also pointed out that a gene (or some genes) located somewhere on chromosome 20 also showed up in the analysis as a difference between the two groups. I think the reason that some men go bald and some do not is probably located in those genes on chromosome 20.


I say this because there was a South Korean Study several years ago that compared the 7 known genes that are associated with alpha-five reductase expression between balding men and hirsute men in South Korea. There was no statistically signifigant difference.

Here is the pubmed on that old study:

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Performing your original search, 5 alpha reductase south korea study alopecia, in PubMed will retrieve 4 records.

J Dermatol Sci. 2003 Apr;31(2):135-41.

Analysis of genetic polymorphisms of steroid 5alpha-reductase type 1 and 2 genes in Korean men with androgenetic alopecia.
Ha SJ, Kim JS, Myung JW, Lee HJ, Kim JW.

Department of Dermatology, St. Paul's Hospital, The Catholic University of Korea, 620-56 Junnong 2-dong, Dongdaemun-ku, 130-709, Seoul, South Korea.

BACKGROUND: Genetic polymorphisms of steroid 5alpha-reductase have been studied in androgenetic alopecia in Caucasians, but the genes encoding the two isoenzymes were not associated with male pattern baldness. Genetic polymorphisms and ethnic variations have not been studied for Asians, although it is suggested that racial difference could exist and influence clinical phenotypes. OBJECTIVE: The purpose of our study is to investigate the genetic polymorphisms of steroid 5alpha-reductase type 1 and 2 (SRD5A1 and SRD5A2) genes in Korean population, and to study the association of these polymorphisms with the development, clinical types (female or male pattern) and therapeutic response of androgenetic alopecia. METHODS: Sixty-six patients with androgenetic alopecia and controls consisted of 92 healthy men were included. Twenty-four patients were treated with finasteride for at least 6 months, and clinical responses were assessed by a simple classification. For type 1 isoenzyme, HinfI and NspI restriction fragment length polymorphisms (RFLPs) were detected using polymerase chain reaction method. For type 2 isoenzyme, RsaI RFLPs detected valine/leucine polymorphisms at codon 89, and MowI RFLPs detected alanine/threonine polymorphisms at codon 49. RESULTS: We could not find any significant associations of the genetic polymorphisms of these two isoenzyme genes with androgenetic alopecia in Koreans (P>0.05). These polymorphisms were not associated with the clinical types of baldness or the response to finasteride (P>0.05). CONCLUSION: These results suggest that polymorphisms of SRD5A1 and SRD5A2 genes may not be directly associated with the development of baldness or generation of different clinical phenotypes.


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Me again guys.......................................but we KNOW via other studies that balding scalp has been shown to have 2 to even 2.5 times more DHT present than hirsuite occipital scalp (sides of the head) right. But if the alpha-five reducase genes are the same (at least in Koreans.....which is probably true for the rest of us), what gives?

Perhaps guys with male pattern baldness have more 3-beta HSD or 17 beta HSD or more NADPH in their scalp tissues? Perhaps this is what is encoded for on Chromosome 20, or P2RY5, or Sox21, EDA2R, or 3q26[9]. Its interesting to speculate.

Perhaps the genes that encode for baldness on chromosome 20 somehow fundamentally design the follicles' DNA in your balding area to react very negatively to DHT once it gets past a certain threshold?


Im kinda inclined to think its more of the former than the latter, and the mix of more CAG repeat mutations on that androgen receptor gene coupled with more DHT being created locally because of more of the enzymes upstream of alpha five reductase in effect creating more alpha five reductase from testosterone. Its interesting to speculate, but the 3-beta HSD increased presence at least does have a little backing via Sawaya.

 

[dopey]

I had read a paper where the researchers implicated oxidative 3a-HSD as a culprit. It caused a backconversion of the weaker androgens to DHT.

 

[squeegee]

I had read a paper where the researchers implicated oxidative 3a-HSD as a culprit. It caused a backconversion of the weaker androgens to DHT.

So, a good prebiotic/probiotic will do the job????? Really interesting thread Michael !