Androgen-inducible TGF-beta1 from balding dermal papilla cells inhibits epithelial cell growth: a clue to understand paradoxical effects of androgen on human hair growth.

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FASEB J 2002 Dec;16(14):1967-9

Androgen-inducible TGF-beta1 from balding dermal papilla cells inhibits epithelial cell growth: a clue to understand paradoxical effects of androgen on human hair growth.

We attempted establishing an in vitro coculture system by using human dermal papilla cells (DPCs) from androgenetic alopecia (AGA) and keratinocytes (KCs) to explore the role of androgens in hair growth regulation. Androgen showed no significant effect on the growth of KCs when they were cocultured with DPCs from AGA. Because the expressions of mRNA of androgen receptor (AR) decreased during subcultivation of DPCs in vitro, we transiently transfected the AR expression vector into the DPCs and cocultured them with KCs. In this modified coculture, androgen significantly suppressed the growth of KCs by approximately 50%, indicating that overexpression of AR can restore the responsiveness of the DPCs to androgen in vivo. We found that androgen stimulated the expression of TGF-beta1 mRNA in the cocultured DPCs. ELISA assays demonstrated that androgen treatment increased the secretion of both total and active TGF-beta1 in the conditioned medium. Moreover, the neutralizing anti-TGF-beta1 antibody reversed the androgen-elicited growth inhibition of KCs in a dose-dependent manner. These findings suggest that androgen-inducible TGF-beta1 derived from DPCs of AGA is involved in epithelial cell growth suppression in our coculture system, providing the clue to understand the paradoxical effects of androgens for human hair growth.

Dermatol Surg 2002 Aug;28(8):678-85

Fluridil, a rationally designed topical agent for androgenetic alopecia: first clinical experience.

BACKGROUND: Fluridil, a novel topical antiandrogen, suppresses the human androgen receptor. While highly hydrophobic and hydrolytically degradable, it is systemically nonresorbable. In animals, fluridil demonstrated high local and general tolerance. OBJECTIVE: To evaluate the safety and efficacy of a topical anti- androgen, fluridil, in male androgenetic alopecia. METHODS: In 20 men, for 21 days, occlusive forearm patches with 2, 4, and 6% fluridil, isopropanol, and/or vaseline were applied. In 43 men with androgenetic alopecia (AGA), Norwood grade II-Va, 2% fluridil was evaluated in a double-blind, placebo-controlled study after 3 months clinically by phototrichograms, hematology, and blood chemistry including analysis for fluridil, and at 9 months by phototrichograms. RESULTS: Neither fluridil nor isopropanol showed sensitization/irritation potential, unlike vaseline. In all AGA subjects, baseline anagen/telogen counts were equal. After 3 months, the average anagen percentage did not change in placebo subjects, but increased in fluridil subjects from 76% to 85%, and at 9 months to 87%. In former placebo subjects, fluridil increased the anagen percentage after 6 months from 76% to 85%. Sexual functions, libido, hematology, and blood chemistry values were normal throughout, except that at 3 months, in the spring, serum testosterone increased within the normal range equally in placebo and fluridil groups. No fluridil or its decomposition product, BP-34, was detectable in the serum at 0, 3, or 90 days. CONCLUSION: Topical fluridil is nonirritating, nonsensitizing, nonresorbable, devoid of systemic activity, and anagen promoting after daily use in most AGA males.

Transgenic Res 2002 Jun;11(3):241-7

Inducible, reversible hair loss in transgenic mice.

Telogen effluvium is a common type of hair loss. Although the morphological changes associated with telogen effluvium have been well characterized, the underlying molecular mechanisms remain unknown, and no animal models have been developed. We report here that inducible transgenic mice expressing high levels of the transcription factor, tTA (tetracycline transactivator), plus a reporter luciferase gene, show a reversible hair loss phenotype. Skin of these mice exhibits an increase in the number of hair follicles at the telogen phase, but a decreased number of follicles at the anagen phase. These changes resemble skin pathology seen in patients with telogen effluvium, which suggests that the inducible transgenic mice may be useful as a model for this disorder. Moreover, since overexpression of several other transgenes failed to cause skin pathology, the present findings also indicate types of molecular abnormalities that may cause reversible hair loss.

J Cardiovasc Risk. 2003 Jun;10(3):227-31.

Hair loss, insulin resistance, and heredity in middle-aged women. A population-based study.

CONTEXTThe association of androgenic alopecia (AGA) with insulin resistance, coronary artery disease and hypercholesterolemia has been previously reported in men, but no such association has been reported in women with female androgenic alopecia (AGA). Female AGA has usually been linked with hyper-androgenism and hirsutism and, most recently, also with polycystic ovarian syndrome (PCOS), even though epidemiological documentation of the latter association is scanty. Polycystic ovarian syndrome is quite common among Caucasian women, and its association with insulin resistance is well documented.OBJECTIVES AND DESIGNThe aim of this study was to obtain a more precise estimation of the prevalence on female AGA and to describe its possible connections with insulin resistance linked parameters and with paternal and maternal family history of alopecia. A cross-sectional population based cohort survey was carried out in the City of Oulu, Finland in 1998.SETTING AND PARTICIPANTSAs a part of a population based cohort study the hair status of 324 women aged 63 years was assessed by a modification of Ludwig's scale. The background data consisting of anthropometric measures (weight, height, body mass index, waist, hip and neck circumferences), smoking status, chronic diseases and their medication as well as the family history of AGA were collected by questionnaires and interviews made by study nurses and in clinical examination. Blood samples for laboratory tests were taken on the same occasion.RESULTSThe prevalence of extensive loss of hair (at least grade II or III on Ludwig's scale) was quite high (31.2%). The insulin resistance associated parameters, such as waist and neck circumferences, abdominal obesity measured by waist-to-hip ratio, mean insulin concentration (11.3 mU/l versus 9.95 mU/l, p=0.02) or urinary albumin-to-creatinine ratio (1.80 versus 1.58, p=0.01), were significantly higher in women with extensive hair loss compared to those with normal hair or only minimal hair loss (grade I on Ludwig's scale). The women belonging to the highest quintiles of neck or waist circumferences had significantly increased risk for extensive hair loss compared to those with normal hair or minimal hair loss, the unadjusted ORs being 2.25 (95% CI, 1.26-4.03) and 1.75 (95% CI, 1.00-3.07), respectively. Similarly in women with hyperinsulinemia (fs-insulin >10 mU/l), microalbuminuria (urinary albumin-to-creatinine ratio exceeding the highest microalbuminuria decile (>2.5 mg/mmol) and paternal history of AGA the ORs for alopecia were increased being 1.65 (95% CI, 1.02-2.67), 2.39 (95% CI, 1.21-4.73) and 2.08 (95% CI, 1.26-3.44). All of these ORs, except those for highest quintiles of waist and neck circumferences remained significant in multiple adjusted models.CONCLUSIONSAccording to the results of this study, female AGA (grade II or III on Ludwig's scale) was quite common among Finnish women aged 63 years. Our results support the hypothesis that women with some markers of insulin resistance have significantly increased risk for female AGA. Paternal history of alopecia seemed to be more common in female AGA compared to women with normal or minimal loss of hair.

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