Characterization of distinct microbiota associated with androgenetic alopecia patients treated and untreated with platelet-rich plasma(PRP)

Background:Androgenic alopecia(AGA)is the most common type of hair loss in men,and there are many studies on the treatment of hair loss by platelet-rich plasma(PRP).The human scalp contains a huge microbiome,but its role in the process of hair loss remains unclear,and the relationship between PRP and the microbiome needs further study.Therefore,the purpose of this study was to investigate the effect of PRP treatment on scalp microbiota composition.Methods:We performed PRP treatment on 14 patients with AGA,observed their clinical efficacy,and collected scalp swab samples before and after treatment.The scalp microflora of AGA patients before and after treatment was characterized by amplifying the V3-V4 region of the 16 s RNA gene and sequencing for bacterial identification.Results:The results showed that PRP was effective in the treatment of AGA patients,and the hair growth increased significantly.The results of relative abundance analysis of microbiota showed that after treatment,g_Cutibacterium increased and g_Staphylococcus decreased,which played a stable role in scalp microbiota.In addition,g_Lawsonella decreased,indicating that the scalp oil production decreased after treatment.Conclusions:The findings suggest that PRP may play a role in treating AGA through scalp microbiome rebalancing.

Androgen signaling inhibits de novo lipogenesis to alleviate lipid deposition in zebrafish

Testosterone is closely associated with lipid metabolism and known to affect body fat composition and muscle mass in males.However,the mechanisms by which testosterone acts on lipid metabolism are not yet fully understood,especially in teleosts.In this study,cyp17a1-/-zebrafish(Danio rerio)exhibited excessive visceral adipose tissue(VAT),lipid content,and up-regulated expression and activity of hepatic de novo lipogenesis(DNL)enzymes.The assay for transposase accessible chromatinwithsequencing(ATAC-seq)results demonstrated that chromatin accessibility of DNL genes was increased in cyp17a1-/-fish compared to cyp17a1+/+male fish,including stearoyl-CoA desaturase(scd)and fatty acid synthase(fasn).Androgen response element(ARE)motifs in the androgen signaling pathway were significantly enriched in cyp17a1+/+male fish but not in cyp17a1-/-fish.Both androgen receptor(ar)-/-and wildtype(WT)zebrafish administered with Ar antagonist flutamide displayed excessive visceral adipose tissue,lipid content,and up-regulated expression and activity of hepatic de novo lipogenesis enzymes.The Ar agonist BMS-564929 reduced the content of VAT and lipid content,and down-regulated acetyl-CoA carboxylase a(acaca),fasn,and scd expression.Mechanistically,the rescue effect of testosterone on cyp17a1-/-fish in terms of phenotypes was abolished when ar was additionally depleted.Collectively,these findings reveal that testosterone inhibits lipid deposition by down-regulating DNL genes via Ar in zebrafish,thus expanding our understanding of the relationship between testosterone and lipid metabolism in teleosts.

The Pathogenesis and Treatment Progress of Androgenic Alopecia

Androgenic alopecia, also known as seborrheic alopecia, is the most common hair loss disorder in dermatology clinics, mainly characterized by hair follicle miniaturization and progressive hair loss. The etiology and pathogenesis of androgenic alopecia are not clear, but may be related to heredity and androgen metabolism. Currently, minoxidil and finasteride are the only two drugs approved by the U.S. Food and Drug Administration (FDA) for AGA treatment, other treatments include oral minoxidil, hair transplantation, low energy laser therapy (LLLT), platelet-rich plasma (PRP), Chinese medicine microneedles, and combination therapy. With the development of medicine and science, we have ushered in the era of biologics and targeted therapy. In recent years, a variety of signaling pathways for androgenic alopecia have been found, which may provide a basis for targeted therapy for androgenic alopecia.

Re-Densification Effect of Pressure-Injected Peptide-Hyaluronic Acid Combination on Male Androgenic Alopecia

Introduction: Mechanism of male androgenic alopecia (MAGA) is complex and leads to an excessive hair shedding and decreased hair density. Oral, topical, and injectable autologous treatments demonstrate ability to stimulate hair re-growth, but the response is suboptimal or plateaus off. Synthetic combination of the peptide complex and hyaluronic acid (P-HA) demonstrated hair regrowth in alopecia patients. Electronically-operated pneumatic injections (EPI) generate micro-trauma in the dermis and under wound-healing conditions may enhance regeneration effect of P-HA. Methods: Subjects seeking improvement of their male pattern hair loss (Hamilton-Norwood type 2-4) received the P-HA treatments through EPI. The course included 4 treatments every two weeks over the 8-week period. In 6 months, the hair growth was assessed comparative to baseline by global clinical photography and digital phototrichograms. The treatment safety and tolerability were documented through the whole study period. Results: Twelve men (30-45 years old) completed the treatment course with high tolerability and without adverse events. Post-treatment assessment of the previously bald areas showed improved coverage on the clinical photographs. The phototrichograms demonstrated statistically significant increase in terminal hair density by 36%, cumulative hair thickness by 37%, and follicular units by 20%;all contributing to a 38% increase in cumulated hair density (all p Conclusion: Electronic pneumatic injections are well tolerated and can be safely used for the needle-free administration of the peptide-hyaluronic acid combination in MAGA therapy. We achieved significant hair re-densification in the balding scalp. The exact role of the EPI-induced impact in the hair re-growth mechanism remains to be ascertained. .

Defective Expression of the Gap Junction Protein Pannexin-1 Channel Contributes to the Formation of PCOS-Realted Androgenetic Alopecia

Objective: To determine serum pannexin-1 channel levels and their association with hair loss in women with PCOS diagnosed with female androgenetic alopecia (FAGA). Materials and Methods: Thirty-five women with PCOS who presented with diffuse and treatment-resistant progressive hair loss and were diagnosed with FAGA were included in the study. 25 patients who were diagnosed with female androgenetic alopecia but did not have PCOS were considered as the control group. PCOS and control groups were matched by age. Follicular miniaturization, displacement of terminal hairs with vellus hairs, and a diffuse decrease in hair density were accepted as FAGA in the trcihoscopy examination of the vertex and bitempoaral area. On the third day of the menstrual cycle serum FSH, LH, testosterone, PRL and insulin levels were measured. Insulin resistance was calculated with HOMA-IR. Serum pannexin-1 channel levels of each group were mesured with ELISA. Results: Serum pannexin 1 channels levels of FAGA group due to PCOS were found to be significantly higher than FAGA patients in the control group (2.72 ± 1.09 ng/mL vs 1.65 ± 0.97 ng/mL, p < 0.01). Serum LH, insulin and testosterone levels of PCOS group were significantly higher than controls. HOMA-IR values were significantly higher and >2.5 in the PCOS group compared to the controls. PRL values were similar except for one patient with elevated PRL. Serum FSH values were the same in both groups. A positive and significant correlation was found between pannexin 1 channels levels and HOMA-IR and serum testosterone levels (r = 0.650, p Conclusions: In addition to hyperandrogenemia, increased pannexin 1 channel levels may play a role in the etiology of PCOS associated FAGA, as it impairs the communication between the skin and hair follicle.

Specific alterations of regional myocardial work in strength-trained athletes using anabolic androgenic steroids compared to athletes with genetic hypertrophic cardiomyopathy

Background:Strength-trained athletes using anabolic androgenic steroids(AAS)have left ventricular(LV)hypertrophy and myocardial fibrosis that can lead to sudden cardiac death.A similar feature was described in athletes with hypertrophic cardiomyopathy(HCM),which complicates the diagnosis for clinicians.In this context,we aimed to compare the LV function of the 2 populations by measuring global and regional strain and myocardial work using speckle-tracking imaging.Methods:Twenty-four strength-trained asymptomatic athletes using AAS(AAS-Athletes),22 athletes diagnosed with HCM(HCM-Athletes),and 20 healthy control athletes(Ctrl-Athletes)underwent a resting echocardiography to assess LV function.We evaluated LV global and regional strains and myocardial work,with an evaluation of the constructive work(CW),wasted work,and work efficiency(WE).Results:Compared to Ctrl-Athletes,both AAS-Athletes and HCM-Athletes had a thicker interventricular septum,with maj ored values in HCM-Athletes.LV strain was reduced in AAS-Athletes and even more in HCM-Athletes.Consequently,global WE was significantly diminished in both AAS and HCM-Athletes(93%±2%in Ctrl-Athletes,90%±4%in AAS-Athletes,and 90%±5%in HCM-Athletes(mean±SD);p<0.05).Constructive work and WE regional analysis showed specific alterations,with the basal septal segments preferentially affected in AAS-Athletes,and both septal and apical segments affected in HCM-Athletes.Conclusion:The regional evaluation of myocardial work reported specific alterations of the major LV hypertrophy induced by the regular use of AAS compared to the LV hypertrophy due to HCM.This finding could help clinicians to differentiate between these 2 forms of pathological hypertrophy.

Clinical Study on Application of Xinrun Tongluo Method Based on the Theory of Collateral Diseases in Treating Androgenic Baldness of Blood Heat Wind Dryness Syndrome

[Objectives]To explore the intervention effect of the representative formula of Xinrun Tongluo method,Liangxue Xiaofeng Powder,on the incidence of androgenic alopecia in the syndrome of blood heat and wind dryness.[Methods]A total of 72 patients with androgenic alopecia in Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine from October,2022 to June,2023 were randomly divided into a control group(36 cases,treated with Western medicine)and a treatment group(36 cases,treated with Chinese herbal formula+Western medicine).The short-term and long-term efficacy of the two groups of patients was compared.[Results]The hair microscopic signs and short-term and long-term efficacy of the treatment group were significantly better than those of the control group before and after treatment,with a statistically significant difference(P<0.05).[Conclusions]The representative formula of Xinrun Tongluo method is Liangxue Xiaofeng Powder,which has better clinical efficacy as an auxiliary Western medicine in the treatment of androgenic alopecia patients with blood heat and wind dryness syndrome,and is worthy of further promotion and application in clinical practice.

Use of androgen deprivation therapy in prostate cancer： indications and prevalence

Androgens play a prominent role in the development, maintenance and progression of prostate cancer. The introduction of androgen deprivation therapies into the treatment paradigm for prostate cancer patients has resulted in a wide variety of benefits ranging from a survival advantage for those with clinically localized or locally advanced disease, to improvements in symptom control for patients with advanced disease. Controversies remain, however, surrounding the optimal timing, duration and schedule of these hormonal approaches. Newer hormonal manipulations such as abiraterone acetate have also been investigated and will broaden treatment options for men with prostate cancer, This review highlights the various androgen-directed treatment options available to men with prostate cancer, their specific indications and the evidence supporting each approach, as well as patterns of use of hormonal therapies.

Novel mutation in the ligand-binding domain of the androgen receptor gene （1790p） associated with complete androgen insensitivity syndrome

Mutations in the X-linked androgen receptor （AR） gene cause androgen insensitivity syndrome （AIS）, resulting in an impaired embryonic sex differentiation in 46,XY genetic men. Complete androgen insensitivity （CAIS） produces a female external phenotype, whereas cases with partial androgen insensitivity （PALS） have various ambiguities of the genitalia. Mild androgen insensitivity （MAIS） is characterized by undermasculinization and gynecomastia. Here we describe a 2-month-old 46,XY female patient, with all of the characteristics of CAIS. Defects in testosterone （T） and dihydrotestosterone （DHT） synthesis were excluded. Sequencing of the AR gene showed the presence in exon 6 of a T to C transition in the second base of codon 790, nucleotide position 2369, causing a novel missense Leu790Pro mutation in the ligand-binding domain of the AR protein. The identification of a novel AR mutation in a girl with CAIS provides significant information due to the importance of missense mutations in the ligand-binding domain of the AR, which are able to induce functional abnormalities in the androgen binding capability, stabilization of active conformation, or interaction with coactivators.

In vivo modulation of androgen receptor by androgens

Aim: To study the effect of androgen and antiandrogen on the level of androgen receptor (AR) mRNA. Methods: The total RNA was extracted from the prostate and analyzed by slot blot analysis. The blots were hybridized with AR cDNA probe and 1A probe (internal control) and autoradiography was performed. The intensity of signal was measured with a densitometer and the ratio of AR RNA and 1A RNA was calculated. Results: Androgenic deprivation produced by castration decreased the weight of the prostate and increased the levels of AR mRNA. Treatment of the castrated rats with testostrone increased the weight of prostate and decreased the levels of AR mRNA. Treatment of normal rats with flutamide decreased the weight of the gland and increased the levels Of AR mRNA. Conclusion: Androgens produce proliferative effect on the prostate and negatively regulate the AR transcription.

Dual androgen-response elements mediate androgen regulation of MMP-2 expression in prostate cancer cells

Aim： To characterize the matrix metalloproteinases （MMP）-2 promoter and to identify androgen response elements （AREs） involved in androgen-induced MMP-2 expression. Methods： MMP-2 mRNA levels was determined by reverse transcription-polymerase chain reaction （RT-PCR）. MMP-2 promoter-driven luciferase assays were used to determine the fragments responsible for androgen-induced activity. Chromatin-immunoprecipitation assay and electrophoretic mobility shift assays （EMSA） were used to verify the identified AREs in the MMP-2 promoter. Results： Androgen significantly induced MMP-2 expression at the mRNA level, which was blocked by the androgen antagonist bicalutamide. Deletion of a region encompassing base pairs -1591 to -1259 （relative to the start codon） of the MMP-2 promoter led to a significant loss of androgen-induced reporter activity. Additional deletion of the 5＇-region up to -562 bp further reduced the androgen-induced MMP-2 promoter activity. Sequence analysis of these two regions revealed two putative ARE motifs. Introducing mutations in the putative ARE motifs by site-directed mutagenesis approach resulted in a dramatic loss of androgen-induced MMP-2 promoter activity, indicating that the putative ARE motifs are required for androgen-stimulated MMP-2 expression. Most importantly, the androgen receptor （AR） interacted with both motif-containing promoter regions in vivo in a chromatin immunoprecipitation assay after androgen treatment. Furthermore, the AR specifically bound to the wild-type but not mutated ARE motifs-containing probes in an in vitro EMSA assay. Conclusion： Two ARE motifs were identified to be responsible for androgen-induced MMP-2 expression in prostate cancer cells.

Bulbocavernosus muscle area measurement： a novel method to assess androgenic activity

Serum testosterone does not correlate with androgen tissue activity, and it is critical to optimize tools to evaluate such activity in males. Ultrasound measurement of bulbocavernosus muscle （BCM） was used to assess the relationship between the number of CAG repeats （CAGn） in the androgen receptor （AR） and the BCM size; the changes in the number of CAGn over age were also evaluated. Transperineal ultrasound measurement of the BCM was also performed. AR CAGn were determined by high performance liquid chromatography, and morning hormone levels were determined using immunoassays. Forty-eight men had CAG repeat analysis. Twenty-five were 〈30 years of age, mean 23.7 years （s.d, = 3.24） and 23 were 〉45 years of age, mean 53years （s.d. = 5.58）. The median CAGn was 21 （13-29）. BCM area was greater when the number of CAGn were 〈18 as compared to the number of CAGn 〉24 （P= 0.04）. There was a linear correlation between the number of CAGn and the BCM area R^2= 16% （P= 0.01）. In the 45 to 65-years-old group, a much stronger negative correlation （R^2 = 29%, P= 0.01） was noticed. In the 19 to 29-years-old group, no such correlation was found （R2 = 4%, P = 0.36）. In older men, the number of CAGn increased with age （R^2 = 32%, P= 0.01）. The number of CAGn in the AR correlates with the area of the BCM. Ultrasound assessment of the BCM is an effective surrogate to evaluate end-organ activity of androgens. The number of CAGn may increase with age.

The physiological and pharmacological basis for the ergogenic effects of androgens in elite sports

Androgen doping in power sports is undeniably rampant worldwide. There is strong evidence that androgen administration in men increases skeletal muscle mass, maximal voluntary strength and muscle power. However, we do not have good experimental evidence to support the presumption that androgen administration improves physical function or athletic performance. Androgens do not increase specific force or whole body endurance measures. The anabolic effects of testosterone on the skeletal muscle are mediated through androgen receptor signaling. Testosterone promotes myogenic differentiation of multipotent mesenchymal stem cells and inhibits their differentiation into the adipogenic lineage. Testosterone binding to androgen receptor induces a conformational change in androgen receptor protein, causing it to associate with beta-catenin and TCF-4 and activate downstream Wnt target genes thus promoting myogenic differentiation. The adverse effects of androgens among athletes and recreational bodybuilders are under reported and include acne, deleterious changes in the cardiovascular risk factors, including a marked decrease in plasma high-density lipoproteins （HDL） cholesterol level, suppression of spermatogenesis resulting in infertility, increase in liver enzymes, hepatic neoplasms, mood and behavioral disturbances, and long term suppression of the endogenous hypothalamic-pituitary-gonadal axis. Androgens are often used in combination with other drugs which may have serious adverse events of their own. In spite of effective methods for detecting androgen doping, the policies for screening of athletes are highly variable in different countries and organizations and even existing policies are not uniformly enforced.

Studies on Androgen Receptor mRNA expression in Pancreas,Hypothalamus and Ovary of Androgen Sterilized Rats

Objective To investigate the androgen receptor （AR） mRNA expression in pancreas, hypothalamus and ovary of androgen sterilized rats （ASR）.Methods ASR model was established by subcutaneous injection of testosterone propionate to SD female rats at the age of 9 days. Around the age of 106 days （proestrus）, all rats were killed, serum Δ4-andronestedione （Δ 4-A）, total testosterone （TT）, free testosterone （FT）, insulin （Ins） and C-peptide （C-P） were measured by radioimmunoassay （RIA）. Total RNA in pancreas, hypothalamus and ovary were extracted and the amount of AR mRNA was quantitatedly analyzed by RT-PCR with single base mutant template as inner standard. Results Serum concentrations of Δ4-A, TT, FT, Ins and C-P in ASR model rats were significantly higher than those in control group （P〈0.05, P〈0.01）. The expression of AR mRNA in pancreas, hypothalamus and ovary increased significantly （P〈0. 05, P〈0.01） of model rats as compared with control group. Conclusion The elevated serum androgen levels in ASR model could enhance the expression of AR mRNA levels in pancreas, hypothalamus and ovary, which further induce hyperinsulinemia and anovulation.

Phenotypic heterogeneity of mutations in androgen receptor gene

Androgen receptor （AR） gene has been extensively studied in diverse clinical conditions. In addition to the point mutations, trinucleotide repeat （CAG and GGN） length polymorphisms have been an additional subject of interest and controversy among geneticists. The polymorphic variations in triplet repeats have been associated with a number of disorders, but at the same time contradictory findings have also been reported. Further, studies on the same disorder in different populations have generated different results. Therefore, combined analysis or review of the published studies has been of much value to extract information on the significance of variations in the gene in various clinical conditions. AR genetics has been reviewed extensively but until now review articles have focused on individual clinical categories such as androgen insensitivity, male infertility, prostate cancer, and so on. We have made the first effort to review most the aspects of AR genetics. The impact of androgens in various disorders and polymorphic variations in the AR gene is the main focus of this review. Additionally, the correlations observed in various studies have been discussed in the light of in vitro evidences available for the effect of AR gene variations on the action of androgens.

nfluence of immune inflammation on androgen receptor expression in benign prostatic hyperplasia tissue

This study was designed to investigate the association between immune inflammation and androgen receptor （AR） expression in benign prostatic hyperplasia （BPH）. We retrospectively analyzed 105 prostatectomy specimens. An immune inflammation score for each specimen was defined by combining three immunohistochemical markers （CD4, CD8 and CD20）. The immunohistochemical markers were CD4 and CD8 for T lymphocytes, CD20 for B lymphocytes and AR antibody for the AR in BPH samples. Rates of CD4, CD8, CD20 and AR expression in BPH were 20 （19.0%）, 21 （20.0%）, 101 （96.2%） and 48 （45.7%）, respectively. Total prostate volume （TPV） was higher in the immune inflammation group than in the non-immune inflammation group （62.7 ml vs. 49.2 ml, t=-2.482, P〈0.05）. Patients in the immune inflammation group had a higher serum prostate-specific antigen （PSA） than those in the non-inflammation group （7.5 ng m1-1 vs. 5.4 ng m1-1, t=-2.771, P〈0.05）. Specifically, the immune inflammation group showed a higher rate of AR expression than the non-inflammation group （56.1% vs. 28.2%, χ2=7.665, P〈0.05）. Our study revealed a strong association between immune inflammation and TPV, serum PSA and AR expression in BPH tissue. Prostate hyperplasia caused by an immune inflammatory process may contribute to BPH progression over time. Therefore, the inflammatory response involved in BPH may be a prime therapeutic target.

Androgen and prostatic stroma

<abstract>Aim: To investigate the effect of androgen on the proliferation, differentiation and regression of canine prostatic stromal cells in vivo and human stromal cells in vitro. Methods: Twenty-two dogs, including 15 normal prostate dogs and 7 prostatic hyperplasia dogs, had their serum concentration of testosterone and estrodiol determined by radioimmunoassay before and after castration. The expression of androgen receptor (AR) and estrogen receptor (ER) in the prostate were analysed by immunohistochemistry and semi-quantitative RT-PCR before and after castration. Light microscopy, transmission electron microscopy and TUNEL assay were carried out successively before and after castration to evaluate the prostatic histomorphology. In vitro serum-free cell cultures from human prostatic stroma were established and exposed to dihydrotestosterone (DHT). The proliferation of the cell culture was detected by MTT assay. The expression of TGFβ, bFGF, AR, and smooth muscle cell (SMC) specific proteins (myosin and/or smoothelin) were detected using immunohistochemistry and RT-PCR. The differentiation from fibroblasts to smooth muscle cells was deduced by measuring the expression of SMC specific proteins. Results: Before castration, the serum concentrations of testosterone and estrodiol were not statistically different between normal and hyperplasia groups. Following castration, the serum concentration of testosterone decreased rapidly in 2 days, and the concentration of estrodiol had no significant change compared with the pre-castration data. In the prostate, AR was presented in both the epithelial and stromal cells and the AR mRNA level was higher in hyperplasia than in normal prostate tissues (P<0.05). While ER predominantly existed in the prostate stromal cells and the ER mRNA had no difference between the hyperplasia and the normal group. Within the early phase of castration (<d7), the expression of AR was increased rapidly. Then it gradually dropped to a lower level than that of the pre-castration by the end of d90. The expression of ER remained unchanged in the whole course. The prostatic stromal cells, including SMCs and fibroblasts, diminished and underwent serial pathological changes of atrophy and apoptosis after castration. The atrophic cells were filled with huge intracellular lipofuscin. The expression of SMC myosin declined after castration, coincident with the increase in TGFβ mRNA level and decline in bFGF mRNA level. In vitro, DHT caused a weak increase in the proliferation and expression of SMC-specific proteins (P<0.05). However, DHT and bFGF together stimulated the proliferation of stromal cells significantly more than either agent alone (P<0.01). The combination of DHT and TGFβ greatly enhanced the expression of SMC-specific proteins (P<0.01) more strongly than either alone (P<0.01). Conclusions: The whole prostate gland is an androgen-sensitive organ with both the epithelium and stroma under the control of androgen. Androgen may direct the proliferation, differentiation and regression of stromal cells by regulating the expression of TGFβ, bFGF, AR and smooth muscle cell specific proteins.

Muscle function, physical performance and body composition changes in men with prostate cancer undergoing androgen deprivation therapy

Prostate cancer （PCa） is the most common visceral malignancy in men with androgen deprivation therapy （ADT） the preferred therapy to suppress testosterone production and hence tumor growth. Despite its effectiveness in lowering testosterone, ADT is associated with side effects including loss of muscle mass, diminished muscle strength, decrements in physical performance, earlier fatigue and declining quality of life. This review reports a survey of the literature with a focus on changes in muscle strength, physical function and body composition, due to short-term and long-term ADT. Studies in these areas are sparse, especially well-controlled, prospective randomized trials. Cross-sectional and longitudinal data （up to 2 years） for men with PCa treated with ADT as well as patients with PCa not receiving ADT and age-matched healthy men are presented when available. Based on limited longitudinal data, the adverse effects of ADT on muscle function, physical performance and body composition occur shortly after the onset of ADT and tend to persist and worsen over time. Exercise training is a safe and effective intervention for mitigating these changes and initial guidelines for exercise program design for men with PCa have been published by the American College of Sports Medicine. Disparities in study duration, types of studies and other patient-specific variables such as time since diagnosis, cancer stage and comorbidities may all affect an understanding of the influence of ADT on health, physical performance and mortality.

Androgens and esophageal cancer: What do we know?

Significant disparities exist between genders for the development and progression of several gastrointestinal(GI) diseases including cancer. Differences in incidence between men vs women for colon, gastric and hepatocellular cancers suggest a role for steroid sex hormones in regulation of GI carcinogenesis. Involvement of intrinsic gender-linked mechanisms is also possible for esophageal adenocarcinoma as its incidence is disproportionally high among men. However, the cause of the observed gender differences and the potential role of androgens in esophageal carcinogenesis remains unclear, even though the cancer-promoting role of androgen receptors(AR) shown in other cancers such as prostate and bladder suggests this aspect warrants exploration. Several studies have demonstrated expression of ARs in esophageal cancer. However, only one study has suggested a potential link between AR signaling and outcome- poorer prognosis. Two groups have analyzed data from cohorts with prostate cancer and one of these found a decreased incidence of esophageal squamous and adenocarcinoma after androgen deprivation therapy. However, very limited information is available about the effects of androgen and AR-initiated signaling on esophageal cancer cell growth in vitro and in vivo. Possible mechanisms for androgens/AR involvement in the regulation of esophageal cancer growth are considered, and the potential use of AR as a prognostic factor and clinical target is highlighted, although insufficient evidence is available to support clinical trials of novel therapies. As esophageal adenocarcinoma is a gender linked cancer with a large male predominance further studies are warranted to clarify the role of androgens and ARs in shaping intracellular signaling and genomic responses in esophageal cancer.

Role of insulin and insulin resistance in androgen excess disorders

Insulin has complex effects on cell growth,metabolism and differentiation,and these effects are mediated by a cell-surface bound receptor and eventually a cascade of intracellular signaling events.Among the several metabolic and growth-promoting effects of insulin,insulin resistance is defined as an attenuated effect of insulin on glucose metabolism,primarily the limited export of blood glucose into skeletal muscle and adipose tissue.On the other hand,not all the signaling pathways and insulin-responsive tissues are equally affected,and some effects other than the metabolic actions of insulin are overexpressed.Ovaries and the adrenal glands are two examples of tissues remaining sensitive to insulin actions where insulin may contribute to increased androgen secretion.Polycystic ovary syndrome(PCOS)is the most common form of androgen excess disorder(AED),and its pathogenesis is closely associated with insulin resistance.Patients with idiopathic hirsutism also exhibit insulin resistance,albeit lower than patients with PCOS.Although it is not as evident as in PCOS,patients with congenital adrenal hyperplasia may have insulin resistance,which may be further exacerbated with glucocorticoid overtreatment and obesity.Among patients with severe insulin resistance syndromes,irrespective of the type of disease,hyperinsulinemia promotes ovarian androgen synthesis independently of gonadotropins.It is highly debated in whom and how insulin resistance should be diagnosed and treated among patients with AEDs,including PCOS.It is not suitable to administer an insulin sensitizer relying on only some mathematical models used for estimating insulin resistance.Instead,the treatment decision should be based on the constellation of the signs,symptoms and presence of obesity;acanthosis nigricans;and some laboratory abnormalities such as impaired glucose tolerance and impaired fasting glucose.