Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The androchronogenetic alopecia (AGA) mouse if a mutant strain which expresses androgen-dependent baldness. Daily s.c. injection of testosterone (T) induced thinning of the hair coat along the upper dorsum after 4 weeks of treatment. After 12 to 14 weeks this diffuse alopecia eventually eveloped into a bald area which extended to the middorsum. Dihydrotestosterone was more effective than T in stimulating the onset of AGA. In this model, T produced the alopecia by decreasing the rate of hair growth, decreasing the duration of anagen, and markedly prolonging the duration of telogen. When applied topically at a concentration of 5%, cyproterone acetate delayed the progression of the T-mediated hair loss. However, this inhibitory effect occurred through systemic means as evidenced by decrease in the size of the submaxillary gland. Chronic feeding of androgen-treated female AGA mice with a diet containing 0.01% minoxidil also inhibited the development of alopecia. Skin and core temperatures were found to be higher in minoxidil-treated animals than in the placebo-treated controls. Minoxidil at a topical dose of 1% did not produce any effect. Increasing the dose to 2% caused a slight retardation of the development of alopecia. However, a 60% inhibition was observed at a topical dose of 5% minoxidil after 12 weeks of treatment (p less than 0.03). The data demonstrate that hair loss in the AGA mouse is androgen dependent and that this mutant strain can serve as a suitable model for the screening of compounds, such as antiandrogens and vasodilators, which may influence the balding process.
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PMID:Animal models of androgen-dependent disorders of the pilosebaceous apparatus. 1. The androchronogenetic alopecia (AGA) mouse as a model for male-pattern baldness. 277 56

In men who are genetically predisposed to develop androgenetic alopecia (AGA; male pattern hair loss), endogenous androgens alter scalp hair follicles, resulting in production of vellus-like, miniaturised hair, rather than cosmetically significant terminal hair. This change leads to a progressive decline in visible scalp hair density, readily perceived by the patient as thinning and, eventually, baldness. Dihydrotestosterone (DHT), a metabolite of testosterone produced by the enzyme 5alpha-reductase, has been implicated as the specific androgen in the pathogenesis of AGA. Men genetically deficient in the Type 2 isoenzyme of 5alpha-reductase do not develop AGA. Moreover, Type 2 5alpha-reductase has been detected in scalp hair follicles, and balding scalps contain increased Type 2 5alpha-reductase activity and DHT levels. Taken together, these findings provide a rationale for the use of Type 2 5alpha-reductase inhibitors in the treatment of men with AGA. Finasteride, a specific and potent inhibitor of human Type 2 5alpha-reductase, decreases the formation of DHT from testosterone. Originally developed for the treatment of men with benign prostatic hyperplasia (BPH) as a 5 mg tablet, finasteride was subsequently evaluated as a treatment for AGA. Clinical studies in balding men demonstrated that finasteride reduced scalp DHT levels and improved hair growth, confirming the role of DHT in the pathophysiology of AGA. Dose-ranging studies established the optimal dose of 1 mg/day for the treatment of men with this disorder. Large, multicentre studies established the safety and efficacy of finasteride 1 mg, leading to marketing of Propecia (finasteride 1 mg) as a new treatment for men with AGA.
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PMID:Finasteride, a Type 2 5alpha-reductase inhibitor, in the treatment of men with androgenetic alopecia. 1599 88