Polycystic Ovaries and Premature Male Pattern Baldness

[squeegee]

Polycystic ovaries and premature male pattern baldness are associated with one allele of the steroid metabolism gene CYP17.

Carey AH, Waterworth D, Patel K, White D, Little J, Novelli P, Franks S, Williamson R.
Source

Department of Molecular Genetics, St Mary's Hospital Medical School, Imperial College of Science Technology and Medicine, London, UK.

Abstract

Fourteen Caucasian families with 81 affected individuals have been assessed in which polycystic ovaries/male pattern baldness (PCO/male pattern baldness) segregates as an autosomal dominant phenotype (1). The gene CYP17, coding for P450c17 alpha (17 alpha-hydroxylase; 17/20 lyase) on chromosome 10q24.3 is the rate-limiting step in androgen biosynthesis. We have identified a new single base change in the 5' promoter region of CYP17 by heteroduplex analysis. This creates an additional SP1-type (CCACC box) promoter site, which may cause increased expression. This base change also creates a recognition site for the restriction enzyme MspA1 allowing a simple screening procedure. There is a significant association between the presence of this base change (A2) and the affected state for consecutively identified Caucasian women with PCO as compared either to consecutively matched controls (P = 0.03) with an odds ratio for those with at least one A2 allele of 3.57, or to a random population (P = 0.02) with an odds ratio of 2.50. Within the fourteen families, members with PCO or male pattern baldness have a significant association with the occurrence of at least one A2 allele compared to their normal relatives, with an odds ratio of 2.20 (P = 0.05). The base change does not cosegregate with the affected phenotype within the families showing association, demonstrating that this mutation of CYP17 does not cause PCO/male pattern baldness. Variation in the A2 allele of the CYP17 gene is a significant factor modifying the expression of PCO/male pattern baldness in families where it has been demonstrated to segregate as a single gene disorder, but it is excluded as the primary genetic defect.

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delta 5-3 beta-hydroxysteroid dehydrogenase activity in sebaceous glands of scalp in male-pattern baldness.

Sawaya ME, Honig LS, Garland LD, Hsia SL.
Source

Department of Dermatology and Cutaneous Surgery, University of Miami School of Medicine, Florida 33101.

Abstract

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 delta 5-3 beta-hydroxysteroid dehydrogenase (3 beta HSD), 17 beta-hydroxysteroid dehydrogenase, and testosterone 5 alpha-reductase by the conversion of [3H]dehydroepiandrosterone (DHA) to 3H-delta 4-androstenedione (AD), [3H]testosterone, and [3H]dihydrotestosterone. Homogenates of glands from bald (B) scalp had greater 3 beta HSD activity than homogenates of glands from hairy (H) scalp. After differential centrifugation, 3 beta HSD activity was found mainly in the microsomal and 105,000 X g supernatant fractions. Specific activity of the enzyme based on protein mass was highest in the microsomal fraction; however, the total 3 beta HSD activity in the 105,000 X g supernatent of B glands was significantly (p less than .01) greater than that of H glands. 3 beta HSD 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 microM), pH optima (8.0), or coenzyme requirement for NAD. Since substantial 3 beta HSD activity was present in the cytosol, and cytosol of B glands showed increased 3 beta HSD activity, the increased conversion of DHA to AD may be a critical step for androgenic action and may be responsible for excessive androgenicity in male-pattern baldness.

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Current understanding of androgenetic alopecia. Part I: Etiopathogenesis

http://www.jle.com/e-docs/00/01/8A/2B/article.phtml

 

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Finding different genes involved with male pattern baldness is cool, but I have this feeling we could chase different genes for decades and not figure out the exact combination we need. Even if we find them all it might be decades before we can actually change anything with them safely without causing all kinds of other problems. I just dont see genes as a practical way to treat male pattern baldness anytime soon. Always good though to find new ones.

 

[IDW2BB]

Finding different genes involved with male pattern baldness is cool, but I have this feeling we could chase different genes for decades and not figure out the exact combination we need. Even if we find them all it might be decades before we can actually change anything with them safely without causing all kinds of other problems. I just dont see genes as a practical way to treat male pattern baldness anytime soon. Always good though to find new ones.

Well, I agree that gene therapy for male pattern baldness is going to take a good amount of time, but finding those factors that influence gene expression may be found sooner than we think. After reading the new post buy the admin. regarding how we should present new studies, I will separately post 2 studies that could have some relevance to squeegee's op. (Androgen Receptor CAG Repeat Length Is Associated With Body Fat and Serum SHBG in Boys: A Prospective Cohort Study. and Increased androgen receptor messenger RNA in frontal-parietal hair follicles of women with androgenetic alopecia.)