|MadSci Network: Genetics|
The Male pattern baldness phenotype involves an enzyme called 5-alpha reductase(Randall, 1994). This enzyme is involved in the the conversion of Testosterone to 5-dihydrotestosterone(DHT) which subsequently binds to Androgen receptors regulating gene expression within the cell. So essentially the male pattern baldness phenotype that you are asking about is caused by the activity of the 5-alpha reductase enzyme. The blockage of the 5-alpha reductase activity is one of the strategies currently being investigated for the treatment of male pattern baldness (see Liao, 1994 for review). The conversion of Testosterone to DHT is catalysed by two different 5-alpha reductase isozymes in a tissue specific and development-dependent manner(Thigpen et al, 1993). These isozymes are referred to as Type I and Type II. It is the expression of the Type II 5-alpha reductase expression which appears to be responsible for male pattern baldness (Thigpen et al, 1993). Mapping of the 5-alpha reductase Type I gene using in situ hybridisation has identified the type 1 gene on 5p15 (ie the short arm of chromosome 5) (see Morisette et al, 1996). So this is really the gene that you ask for in your question, the Male pattern baldness gene as it were. Carey et al (1994) have identified another gene, referred to as CYP17, which appears to have some role in the development of polycystic ovaries(PCO) and the male pattern baldness (MPB) phenotypes. The results published by Carey et al(1994) are based on a study carried out on 14 Caucassian families. The observed phenotype has an autosomal dominant mode of inheritance (only one copy of the defective gene is required in order to produce the phenotype). What Carey et al(1994) have found is that there is a statistically significant association between a specific mutation in the CYP17 gene and the MPB/PCO phenotypes. I am not sure how much you know about genetics but the identified mutation involves a base change that produces an additional promoter site and that this increases the expression of the CYP17 gene. Whilst this gene is associated with the MPB/PCO phenotypes it is not considered by Carey et al(1994) to be the primary genetic determinant. This conclusion is based on the fact that the mutation does not co-segregate with the phenotypes (i.e- it is not present in all affected individuals). I hope that this answers your question. Do not hesitate to contact me if there is anything that is unclear (ie-terminology etc. I will be most happy to answer any questions). Best wishes, Robert Deyes Carey AH, Waterworth D, Patel K, White D, Little J, Novelli P, Franks S, Williamson R Polycystic ovaries and premature male pattern baldness are associated with one allele of the steroid metabolism gene CYP17. Hum Mol Genet 1994 Oct;3(10):1873-1876 Liao S Androgen action: molecular mechanism and medical application. J Formos Med Assoc 1994 Sep;93(9):741-751 Morissette J, Durocher F, Leblanc JF, Normand T, Labrie F, Simard J Genetic linkage mapping of the human steroid 5 alpha-reductase type 2 gene (SRD5A2) close to D2S352 on chromosome region 2p23-->p22. Cytogenet Cell Genet 1996;73(4):304-307 Randall VA Role of 5 alpha-reductase in health and disease. Baillieres Clin Endocrinol Metab 1994 Apr;8(2):405-431 Thigpen AE, Silver RI, Guileyardo JM, Casey ML, McConnell JD, Russell DW Tissue distribution and ontogeny of steroid 5 alpha-reductase isozyme expression. J Clin Invest 1993 Aug;92(2):903-910
Try the links in the MadSci Library for more information on Genetics.