Info on male pattern baldness-area and occipital scalp DIFFERENCES:
Increased androgen binding capacity in sebaceous glands in scalp of male-pattern baldness.Sawaya ME, Honig LS, Hsia SL.
Department of Dermatology and Cutaneous Surgery, University of Miami School of Medicine, Florida 33101.
Sebaceous glands were isolated by manual dissection under a microscope from surgical specimens of scalp skin with male pattern baldness and skin specimens of hairy and bald scalp obtained at autopsy. The 800 X g pellet (nuclear fraction) and the 164,000 X g supernatant fraction (cytosol) of homogenates of the sebaceous glands were used for measurements of androgen binding characteristics, using dextran-coated charcoal and sucrose gradient methods. Scatchard plots showed high affinity binding for [3H]dihydrotestosterone (DHT) and [3H]methyltrienolone (R1881). Nuclei prepared from bald scalp contained greater total androgen binding capacity than nuclei of hairy scalp, although Kd values of type I binding were similar (0.68 vs 0.56 nM, respectively). On sucrose gradient, the binding protein from cytosol was found in the 7 to 8S density range. Androgen binding by cytosol of sebaceous glands of hairy scalp had Kd of 1.89 +/- .79 and 2.05 +/- .56 nM for DHT and R1881, respectively, and Bmax of 18.7 +/- 4.4 and 20.0 +/- 4.6 fmol/mg protein for DHT and R1881, respectively. Cytosol from sebaceous glands of bald scalp had Kd values approximately half those of hairy scalp, and Bmax values 50%-100% higher. The bound 3H labeled DHT and R1881 could be partially displaced by testosterone (40-50%), moxestrol (28-32%), promegestone (19-26%), and delta 4-androstenedione (6-12%), but not by dehydroepiandrosterone. These data demonstrate the presence of specific androgen binding protein in sebaceous glands, and that sebaceous glands of bald scalp have greater binding affinity and capacity for androgens than those in hairy scalp. This difference may explain the greater androgenic response in androgenic alopecia.
PMID: 2909628 [PubMed - indexed for MEDLINE]
Post reply
ON GENETICS AND male pattern baldness:
Its known that the variant of the androgen receptor gene is located on the
> x-chromosome and comes from your mother, but the other genes in baldness
An ectodysplasin gene (which is located on the X chromosome, near the AR gene) has now been linked to male pattern baldness. The ectodysplasin signalling system has already been shown to be important in hair biology...do a search on Pubmed for more details. You'll be hearing about this study in the lay media pretty soon, I'm sure:
J Invest Dermatol. 2008 Apr 3 [Epub ahead of print]
EDA2R Is Associated with Androgenetic Alopecia.
Prodi DA, Pirastu N, Maninchedda G, Sassu A, Picciau A, Palmas MA, Mossa A, Persico I, Adamo M, Angius A, Pirastu M.
1Shardna Life Sciences, Pula, Italy.
Androgenetic alopecia (Androgenetic Alopecia) is a common heritable polygenic disorder whose genetics is not fully understood, even though it seems to be X-linked. We carried out an epidemiological survey for Androgenetic Alopecia on 9,000 people from 8 isolated villages of a secluded region of Sardinia (Ogliastra), and identified a large cohort of affected individuals. We genotyped 200 cases and 200 controls (mean kinship 0.001) with the 500k chip array and conducted case-control association analysis on the X chromosome. We identified Xq11-q12 as strongly associated with Androgenetic Alopecia. In particular, we found that rs1352015 located 8 kb from the EDA2R gene showed the best result (P=7.77e(-7)). This region also contains the AR gene, hence we tested both genes in 492 cases and 492 controls. We found that the non-synonymous SNP rs1385699 on EDA2R gave the best result (P=3.9e(-19)) whereas rs6152 on the AR gene is less significant (P=4.17e(-12)). Further statistical analysis carried out by conditioning each gene to the presence of the other showed that the association with EDA2R is independent while the association with AR seems to be the result of linkage disequilibrium. These results give insight into the pathways involved in Androgenetic Alopecia etiology.
Journal of Investigative Dermatology advance online publication, 3 April 2008;
doi:10.1038/jid.2008.60.
PMID: 18385763 [PubMed - as supplied by publisher]
On the Hippocratic wreath and male pattern baldness:
Article
Min Zhang 1, Anna Brancaccio 2, Lorin Weiner 1, Caterina Ectodysplasin regulates pattern formation in the mammalian hair coat Missero 2, Janice L. Brissette 1 *
1Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA
2Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy
email: Janice L. Brissette (
janice.brissette@cbrc2.mgh.harvard.edu)
*Correspondence to Janice L. Brissette, Cutaneous Biology Research Center, Massachusetts General Hospital-East, Bldg. 149, 13th St., Charlestown, MA 02129
Funded by:
National Institutes of Health
Cutaneous Biology Research Center through the Massachusetts General Hospital/Shiseido Co. Ltd. Agreement
Italian Telethon Foundation
TIGEM with funding from Regione Campania
Keywords
Eda • tabby • ectodermal dysplasia • ED1 • Edar
Abstract
Summary: develoIn mammalian skin, hair follicles develop at regular intervals and with site-specific morphologies. This process generates distinct patterns of hair, but the mechanisms that establish these patterns remain largely unknown. Here we present evidence of follicular patterning by ectodysplasin-A1 (Eda-A1), a signaling protein necessary for the proper development of hair and other appendages. In transgenic mice, Eda-A1 was targeted to the epithelial compartment of the ping skin. At periodic locations, multiple hair follicles were induced side by side, without any interfollicular space. These follicles grew into the dermis as a fusion and subsequently branched to create discrete stalks and hair bulbs. Thus, at sites where interfollicular skin normally forms, hair follicles developed instead. This result shows that Eda-A1 can regulate basic developmental decisions, as cells were switched from interfollicular to follicular fates. Given these effects, it is likely that Eda-A1 is among the key regulators of pattern formation in the skin. genesis 37:30-37, 2003. © 2003 Wiley-Liss, Inc.
Me again............perhaps this 'Ectodermal-A1' gene is the one that makes the decisions as your head skin grows up over your head in fetal development and determines where your most androgen-sensitive hair will be (the shape of your hippocratic wreath), or where your best working androgen-receptors will be (Im basing this on a study I saw that showed androgen receptors in sebaceous glands in male pattern baldness subjects were much better at uptaking androgens that receptors from sweat glands from occipital scalp). A working "guess" is forming anyway in my mind about it. Here is another study showing that ectodysplasin 'gene' and the development of the sweat glands (Do you remember how Stephen Foote used to go on about how bald areas of scalp are better at sweating than hairy areas of scalp? Maybe this is a reason why--
--other than the sweat glands in bald scalp receptor-sites probably have more available testosterone around due to the tiny vellus hairs not having as many androgen receptors available to uptake androgen in a competing sense physically:
[Relationship of ectodysplasin gene signaling with development and regeneration of sweat glands][Article in Chinese]
Zhou G, Li H, Fu X.
Key Research Laboratory of the Wound Repair, the 304th Clinical Department, General Hospital of PLA, Beijing, 100037, P.R. China.
OBJECTIVE: To investigate the expression of ectodysplasin (EDA) gene signaling and its relationship with the development and regeneration of sweat glands. METHODS: The articles concerned in the latest years were extensively reviewed. RESULTS: EDA gene is an important signaling pathway associated with the developmental procedure of sweat glands in early fetal stage. Abnormality or depletion of function in sweat glands partially owed to the defect of EDA gene. CONCLUSION: EDA signaling has its biological significance in inducing development and morphogenesis of sweat glands and in maintaining physiological function of skin. It could be a new approach to repair or regenerate the sweat glands for clinical therapy by regulating the expression of EDA gene.
PMID: 16752854 [PubMed - in process]
ON GENES AND DERMAL TISSUES:
http://ghr.nlm.nih.gov/gene=eda
(maybe this gene set being active in a particular way along with a particular variant of the AR-gene are what is necessary for male pattern baldness-to be inherited. I wonder if they can "block" what is necessary in pregnant mothers someday----not that this will help us)
Reviewed August 2006
What is the official name of the EDA gene?
The official name of this gene is “ectodysplasin A.â€
EDA is the gene's official symbol. The EDA gene is also known by other names, listed below.
What is the normal function of the EDA gene?
The EDA gene provides instructions for making a protein called ectodysplasin A. This protein is part of a signaling pathway that plays an important role in development before birth. Specifically, it is critical for interactions between two embryonic cell layers called the ectoderm and the mesoderm. In the early embryo, these cell layers form the basis for many of the body's organs and tissues. Ectoderm-mesoderm interactions are essential for the formation of several structures that arise from the ectoderm, including the skin, hair, nails, teeth, and sweat glands.
The EDA gene provides instructions for producing many slightly different versions of ectodysplasin A. One version, ectodysplasin A1, interacts with a protein called the ectodysplasin A receptor (produced from the EDAR gene). On the cell surface, ectodysplasin A1 attaches to this receptor like a key in a lock. When these two proteins are connected, they trigger a series of chemical signals that affect cell activities such as division, growth, and maturation. Before birth, this signaling pathway controls the formation of ectodermal structures such as hair follicles, sweat glands, and teeth.
How are changes in the EDA gene related to health conditions?
hypohidrotic ectodermal dysplasia - caused by mutations in the EDA gene
More than 80 different mutations in the EDA gene have been identified in people with hypohidrotic ectodermal dysplasia. These mutations cause the X-linked form of the disorder, which accounts for 95 percent of all cases of hypohidrotic ectodermal dysplasia. (X-linked disorders are caused by mutations in genes on the X chromosome, one of the two sex chromosomes.)
Some mutations in the EDA gene change single DNA building blocks (base pairs), whereas other mutations insert or delete genetic material in the gene. These changes lead to the production of a nonfunctional version of the ectodysplasin A protein. This abnormal protein cannot trigger chemical signals needed for normal interactions between the ectoderm and the mesoderm. Without these signals, hair follicles, teeth, sweat glands, and other ectodermal structures do not form properly, leading to the characteristic features of hypohidrotic ectodermal dysplasia.
Where is the EDA gene located?
Cytogenetic Location: Xq12-q13.1
Molecular Location on the X chromosome: base pairs 68,752,635 to 69,176,046
