Evidence for a functional interaction of WNT10A and EBF1 in male-pattern baldness

More than 300 genetic risk loci have been identified for male pattern baldness (MPB) but little is known about the exact molecular mechanisms through which the associated variants exert their effects on MPB pathophysiology. Here, we aimed at further elucidating the regulatory architecture of the MPB risk locus on chromosome (chr.) 2q35, where we have previously reported a regulatory effect of the MPB lead variant on the expression of WNT10A. A HaploReg database research for regulatory annotations revealed that the association signal at 2q35 maps to a binding site for the transcription factor EBF1, whose gene is located at a second MPB risk locus on chr. 5q33.3. To investigate a potential interaction between EBF1 and WNT10A during MPB development, we performed in vitro luciferase reporter assays as well as expression analyses and immunofluorescence co-stainings in microdissected human hair follicles. Our experiments confirm that EBF1 activates the WNT10A promoter and that the WNT10A/EBF1 interaction is impacted by the allelic expression of the MPB risk allele at 2q35. Expression analyses across different hair cycle phases and immunhistochemical (co)stainings against WNT10A and EBF1 suggest a predominant relevance of EBF1/WNT10A interaction for hair shaft formation during anagen. Based on these findings we suggest a functional mechanism at the 2q35 risk locus for MPB, where an MPB-risk allele associated reduction in WNT10A promoter activation via EBF1 results in a decrease in WNT10A expression that eventually results in anagen shortening, that is frequently observed in MPB affected hair follicles. To our knowledge, this study is the first follow-up study on MPB that proves functional interaction between two MPB risk loci and sheds light on the underlying pathophysiological mechanism at these loci.

Proscar and Propecia: the Gary and Jerry show

Tracking down the metabolic basis of a remarkable human single-gene genetic disease provided the insight required to discover drugs to prevent prostate gland growth in aging men (benign prostatic hyperplasia, BPH) and prevent hair loss in men (male pattern baldness). Victims of this genetic disease are born with the appearance of females and are recognized as such. However, at puberty, they undergo a transformation and develop the characteristics of males. The underlying genetic defect is a mutation in the gene that codes for the enzyme 5-alpha reductase (5AR), which promotes conversion of testosterone (T) into the more potent male sex hormone dihydrotestosterone (DHT). Lack of sufficient DHT in utero prevents the full expression of male anatomy at birth, an issue that is corrected at the time of puberty when a surge of male sex hormones occurs. These men have a very small prostate gland that never grows, do not lose their hair, and do not get acne. This strongly suggests that DHT is the causative agent of BPH, male pattern baldness, and acne. An inhibitor of 5AR would create the functional equivalent of the genetic defect and would be expected to be effective in shrinking an enlarged prostate gland and slowing or preventing hair loss and acne in men. Finasteride is such an inhibitor and has met expectations. It is marketed as Proscar for BPH and Propecia for male pattern baldness. Finasteride is a teratogen (can cause birth defects) and has not been developed for acne for that reason.

The potential of androgenic alopecia management from plant derivatives

Hair loss or alopecia is a common dermatological issue that can affect millions of human population of all ages and both gender, male and female. Frequently, alopecia has been found to be associated with significant adverse effects or reduction of psychological and self-esteem. Consequently, this may lead to psychological problems such as depression and anxiety, thus it may negatively impact the quality of life as well. There are several types of hair loss including androgenetic alopecia (AGA), alopecia areata (AA), alopecia totalis (AT), Alopecia Universalis (AU), cicatricial alopecia (CA), senescent alopecia (SA), traction alopecia (TA) and telogen effluvium. However, this review will focus on the androgenic alopecia only. Androgenic alopecia (AGA) also known as male pattern baldness is referred to as hair loss that often occurs in men after puberty caused by the androgen. In addition, this review will discuss on the hair growth cycles and their mechanism on the androgenic alopecia and lastly the management of androgenic alopecia using plant derivatives and methods used in order to prolong the efficacy of androgenetic alopecia treatment.

Review on Hair Problem and its Solution

Hair is simple in structure. Hair is formed of an extreme protein called Keratin. Cleanser may be a hair care item, ordinarily as a gooey fluid, that's utilized for cleaning hair. the problems related with it incorporates male pattern baldness, raucous hair, absence of hair volume, molding, youthful turning gray, dandruff, diminishing of hair, bluntness then on. Male pattern baldness are often caused due to various reasons, for instance , hereditary propensities, ecological triggers and presentation to synthetic compounds, medications, healthful inadequacy, outrageous pressure or long ailment then on. Gentle dandruff can for the foremost part be settled by washing the hair a day with a mellow cleanser hair. Sedated hostile to dandruff cleanser clean both the hair and scalp and leave the hair reasonable, not bother sebaceous organs. It contains an enemy of microbial to forestall development of expanded occurrence of microorganisms. Dynamic material ought not sharpen the scalp and diminish the extent of tingling and scaling. the most objective of article give idea about hairs problem, the way to solve these problems with cost effectiveness and also help to pick the which sort of treatment with selective dosage form preparation as per hairs problem by researcher for society. Keywords Antidandruff, Surfactants, Shampoo, Scalps

SUN-049 Male Pattern Baldness and Waist-Hip Ratio as Markers of Arterial Stiffness in Transgender Men Undergoing Long-Term Testosterone Therapy

Introduction: Association between male pattern baldness, also called androgenetic alopecia (AGA) and risk of coronary artery disease has been suggested by several epidemiological studies. Exogenous testosterone (T) therapy in transgender men (TM) promotes the development of alopecia in genetically susceptible individuals, and increases facial and body hair, muscle mass (MM) and visceral fat. The outcome of a long-term androgenic therapy over the functional properties of large arteries and the cardiovascular system of TM are not well stablished. Objective: To investigate the possible association between AGA and arterial stiffness assessed by measurement of carotid-femoral pulse wave velocity (VOPcf) and intima-media thickness carotid artery (cIMT) in TM receiving long-term T therapy. Methods: Forty-six TM (mean age: 43 ± 10 yo) undergoing T therapy (mean time of treatment duration: 13 ± 10 y; mean serum T levels: 611 ± 439 ng/dL) were evaluated in a cross-sectional study. Hair pattern (Ferriman & Gallway scale), grades of male pattern baldness (Hamilton-Norwood scale) and waist-hip ratio (WHR) were analyzed. Subjects were considered to have AGA if they have vertex alopecia (grade ≥ 3). Arterial Hypertension was defined as systolic blood pressure > 140 and/or diastolic blood pressure > 90mmHg or under pharmacological treatment, and dyslipidemia as total cholesterol ≥ 240 mg/dL and/or LDL-c≥ 160 mg/dL and/or HDL-c < 40 mg/dL and/or triglycerides > 200 mg/dL, or under pharmacological treatment. Current smoking has been investigated. The aortic stiffness, assessed by VOPcf and cIMT, was measured using the Complior® device and carotid ultrasound, respectively. Results: TM’s Ferriman degree was 21 ± 6 and AGA was identified in 70% of them. The WHR was 0.9 ± 0.1. TM with AGA showed higher cIMT than TM without AGA (0.66 ± 0.1mm vs. 0.54 ± 0.07mm, p = 0.001), as well as higher WHR (0.93 ± 0.08 vs.0.87 ± 0.04, p = 0.02), higher score in terminal body hair (Ferriman 23 ± 6 vs. 18 ± 6, p = 0.007) and higher frequency of hypertension (94% vs. 6%, p = 0.01). The cIMT positively correlated with age (p = 0.01) and WHR (p = 0.002). The VOPcf was positively correlated with the age (p = 0.0001), androgen treatment duration (p = 0.01) and WHR (p = 0.04). There was a positive correlation between androgen treatment duration and WHR (p = 0.01). There was no difference in the VOPcf values, age, T treatment duration, serum T levels, frequency of dyslipidemia and smoking between the groups. Conclusion: The severe vertex AGA pattern may be considered a possible marker of arterial stiffness in TM undergoing long-term testosterone therapy.

Untargeted Metabolomics and Steroid Signatures in Urine of Male Pattern Baldness Patients after Finasteride Treatment for a Year

Male pattern baldness (MPB) has been associated with dihydrotestosterone (DHT) expression. Finasteride treats MPB by inhibiting 5-alpha reductase and blocking DHT production. In this study, we aimed to identify metabolic differences in urinary metabolomics profiles between MPB patients after a one-year treatment with finasteride and healthy controls. Untargeted and targeted metabolomics profiling was performed using liquid chromatography-mass spectrometry (LC-MS). We hypothesized that there would be changes in overall metabolite concentrations, especially steroids, in the urine of hair loss patients treated with finasteride and normal subjects. Untargeted analysis indicated differences in steroid hormone biosynthesis. Therefore, we conducted targeted profiling for steroid hormone biosynthesis to identify potential biomarkers, especially androgens and estrogens. Our study confirmed the differences in the concentration of urinary androgens and estrogens between healthy controls and MPB patients. Moreover, the effect of finasteride was confirmed by the DHT/T ratio in urine samples of MPB patients. Our metabolomics approach provided insight into the physiological alterations in MPB patients who have been treated with finasteride for a year and provided evidence for the association of finasteride and estrogen levels. Through a targeted approach, our results suggest that urinary estrogens must be studied in relation to MPB and post-finasteride syndrome.