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Research Resources:
Alopecia, hair loss abstracts - Dream Pharmaceuticals, Rx online
Mol Endocrinol. 2002 Nov;16(11):2538-46.
A novel mutation in helix 12 of the vitamin D receptor impairs coactivator interaction and causes hereditary 1,25-dihydroxyvitamin D-resistant rickets without alopecia.
Malloy PJ, Xu R, Peng L, Clark PA, Feldman D.
Department of Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
Hereditary vitamin D-resistant rickets (HVDRR) is a genetic disorder most often caused by mutations in the vitamin D receptor (VDR). The patient in this study exhibited the typical clinical features of HVDRR with early onset rickets, hypocalcemia, secondary hyperparathyroidism, and elevated serum concentrations of alkaline phosphatase and 1,25-dihydroxyvitamin D [1,25-(OH)(2)D(3)]. The patient did not have alopecia. Assays of the VDR showed a normal high affinity low capacity binding site for [(3)H]1,25-(OH)(2)D(3) in extracts from the patient's fibroblasts. However, the cells were resistant to 1,25-dihydroxyvitamin D action as demonstrated by the failure of the patient's cultured fibroblasts to induce the 24-hydroxylase gene when treated with either high doses of 1,25-(OH)(2)D(3) or vitamin D analogs. A novel point mutation was identified in helix H12 in the ligand-binding domain of the VDR that changed a highly conserved glutamic acid at amino acid 420 to lysine (E420K). The patient was homozygous for the mutation. The E420K mutant receptor recreated by site-directed mutagenesis exhibited many normal properties including ligand binding, heterodimerization with the retinoid X receptor, and binding to vitamin D response elements. However, the mutant VDR was unable to elicit 1,25-(OH)(2)D(3)-dependent transactivation. Subsequent studies demonstrated that the mutant VDR had a marked impairment in binding steroid receptor coactivator 1 (SRC-1) and DRIP205, a subunit of the vitamin D receptor-interacting protein (DRIP) coactivator complex. Taken together, our data indicate that the mutation in helix H12 alters the coactivator binding site preventing coactivator binding and transactivation. In conclusion, we have identified the first case of a naturally occurring mutation in the VDR (E420K) that disrupts coactivator binding to the VDR and causes HVDRR.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12403843&dopt=Abstract
J Invest Dermatol. 2002 Oct;119(4):920-2.
A novel missense mutation affecting the human hairless thyroid receptor interacting domain 2 causes congenital atrichia.
Klein I, Bergman R, Indelman M, Sprecher E.
Department of Dermatology and Laboratory of Molecular Dermatology, Rambam Medical Center, Haifa, Israel.
Congenital atrichias represent a large and heterogeneous group of inherited hair disorders. In this report, we describe a patient affected with alopecia universalis congenita (MIM 203655). Sequence analysis revealed a G to A transition at cDNA position 3034 of the hairless hr gene present in a homozygous state in the patient and in a heterozygous state in the patient's mother, and absent in the patient's sister. The mutation is predicted to result in the substitution of an asparagine residue for an aspartate amino acid (D1012N) at a position previously shown in the rat to affect hairless binding to thyroid hormone receptor. This study presents the first evidence in humans for the functional importance of the hairless thyroid receptor interacting domain 2.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12406339&dopt=Abstract
AOK.PTE.hu
Enzyme hydrolysis, solid phase extraction, methoxym-silyl derivatization and capillary gas chromatographic analysis were used to examine the changes in urinary steroid metabolites in men with androgenic alopecia. A total of 23 men with androgenic alopecia and 7 age-matched control healthy men collected 24-h urine. Significantly increased values were found in the metabolites of testosterone (T): androsterone (A) (p<0.02), and etiocholanolone (E) (p<0.05) in patients with androgenic alopecia, compared to the control values. Elevated levels of 16-hydroxy-dehydroepiandrosterone (16-OHD) (p<0.03) and cortisol (F) (P<0.05) were found, but the levels of cortisol metabolites were unchanged. Calculating the ratio of total 5 alpha/5 beta metabolites provided information on the activity of 5 alpha-reductase. The ratio of total 5 alpha/5 beta metabolites was increased in the patients showing the increased 5 alpha-reductase activity. The elevated 16-OHD level could be indicative of patients who had mild hyperadrenal activity.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12406594&dopt=Abstract
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