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Journal of Cosmetic Dermatology Aug 2019The second most common alopecia-Androgenetic alopecia (AGA)-occurs due to hormonal imbalance. Dihydrotestosterone (DHT) an androgenic hormone is a sex steroid, produced... (Review)
Review
The second most common alopecia-Androgenetic alopecia (AGA)-occurs due to hormonal imbalance. Dihydrotestosterone (DHT) an androgenic hormone is a sex steroid, produced in the gonads. The target sites of DHT are similar to that of testosterone, and it attaches easily remaining bound for 53 minutes as compared to 35 minutes of testosterone. Excess of DHT causes miniaturization of hair reducing the anagen phase and increasing the telogen phase leading to hair loss. Normally up to ten percent of testosterone in the body irreversibly gets converted into DHT by the action of enzyme 5-alpha-reductase. Inadequate blood flow to the scalp can also be another reason for hair loss encountered due to lower oxygen and nutrients reaching it. AGA affects both sexes; however in males, it leads to major hair loss. Conventional drugs such as minoxidil and finasteride are widely used for the treatment. However, several drawbacks such as allergic contact dermatitis, burning, ejaculation disorder, and decreased libido are reported. Available literature suggests the role of herbal drugs to have the action against 5-alpha-reductase enzyme inhibiting it and reducing the hair loss. This can be further potentiated since they exhibit lesser side effects. Recent advancements observed in the medicinal, cosmetic, and engineering fields can prove to be an asset. This article focuses on herbs which can be used in AGA. A review of Saw palmetto (Serenoa repens), Green tea (Camellia sinensis), Pumpkin seed (Curcurbita pepo), Rosemary (Rosmarinus officinalis), Grape seed (Vitis vinifera), and Licorice (Glycyrrhiza glabra) is attempted.
Topics: 5-alpha Reductase Inhibitors; Alopecia; Camellia sinensis; Cucurbita; Dihydrotestosterone; Glycyrrhiza; Hair; Humans; Plant Extracts; Serenoa; Vitis
PubMed: 30980598
DOI: 10.1111/jocd.12930 -
Indian Journal of Pediatrics Jun 2023Micropenis, i.e., a structurally normal but abnormally small penis is defined as stretched penile length (SPL) 2.5 SD below the mean for age and sexual stage. Several... (Review)
Review
Micropenis, i.e., a structurally normal but abnormally small penis is defined as stretched penile length (SPL) 2.5 SD below the mean for age and sexual stage. Several studies worldwide have published country-specific normative data on SPL; an appropriate cutoff for evaluation of micropenis as per international standards would be below 2 cm at birth and below 4 cm after 5 y of age. Testosterone production by fetal testes, its conversion to dihydrotestosterone (DHT) and its action on the androgen receptor is necessary for normal penile development. Hypothalamo-pituitary disorders (gonadotropin or growth hormone deficiencies), genetic syndromes, partial gonadal dysgenesis, testicular regression, disorders of testosterone biosynthesis and action constitute the various etiologies of micropenis. Associated hypospadias, incomplete scrotal fusion, and cryptorchidism are suggestive of disorders of sex development (DSD). Along with basal and human chorionic gonadotropins (HCG)-stimulated gonadotropins, testosterone, DHT, and androstenedione levels, karyotype assessment is equally important. Treatment aims at attaining penile length sufficient enough for urination and to perform sexual function. Hormonal therapy with intramuscular or topical testosterone, topical DHT or recombinant follicle stimulating hormone (FSH) and luteinizing hormone (LH) should be attempted in the neonatal or infancy period. The role of surgery for micropenis is limited and has variable patient satisfaction and complication outcomes. There is a need for long-term studies on the adult SPL achieved following treatment for micropenis in infancy and childhood.
Topics: Male; Infant, Newborn; Adult; Humans; Child; Genital Diseases, Male; Testosterone; Penis; Dihydrotestosterone; Gonadotropins; Follicle Stimulating Hormone
PubMed: 37079255
DOI: 10.1007/s12098-023-04540-w -
Neurobiology of Disease Jul 2020Microglia-induced neuroinflammation plays a vital role in the etiology and progression of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease...
Microglia-induced neuroinflammation plays a vital role in the etiology and progression of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and multiple sclerosis. The neuroprotective role of androgens, including testosterone and its metabolite dihydrotestosterone (DHT), has been increasingly demonstrated in these diseases, but few studies investigated the effects of androgen on neuroinflammation. This study investigated the role of DHT in lipopolysaccharide (LPS)-induced neuroinflammation, neuronal damage and behavioral dysfunction, as well as underlying mechanisms. We showed that DHT inhibited LPS-induced release of proinflammatory factors, including TNF-α, IL-1β, IL-6; iNOS, COX-2, NO, and PGE2 in BV2 cells and primary microglia by suppressing the TLR4-mediated NF-κB and MAPK p38 signaling pathways, thus protecting SH-SY5Y neurons from inflammatory damage induced by activated microglia. In an LPS-induced neuroinflammation mouse model, endogenous DHT depletion by castration exacerbated inflammatory responses by upregulating the levels of TNF-α, IL-1β, IL-6, iNOS, and COX-2 in the serum and brain by increasing the LR4-mediated NF-κB and MAPK pathway activation, but these effects were restored by exogenous DHT supplementation. Moreover, DHT also regulated the mRNA levels of the anti-inflammatory cytokines IL-10 and IL-13 in the brain. In addition, DHT modulated the expression of Aβ, the apoptotic proteins caspase-3, Bcl-2, and Bax, and synaptophysin, as well as neuronal damage in LPS-treated mouse brains. Further behavioral tests revealed that DHT ameliorated LPS-induced spatial and learning impairment and motor incoordination, and partly improved the locomotor activity in LPS-injected mice. Therefore, this study suggests that DHT exerts anti-neuroinflammatory and neuroprotective effects; thus, androgen replacement therapy is a potential therapeutic strategy for improving cognitive and behavioral function in neuroinflammation-related diseases.
Topics: Androgens; Animals; Anti-Inflammatory Agents; Brain; Cyclooxygenase 2; Cytokines; Dihydrotestosterone; Inflammation; Lipopolysaccharides; MAP Kinase Signaling System; Mice; Microglia; NF-kappa B; Neurons; Neuroprotection; Neuroprotective Agents; Nitric Oxide Synthase Type II; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha
PubMed: 32087283
DOI: 10.1016/j.nbd.2020.104814 -
The Canadian Veterinary Journal = La... Apr 2018Many articles published in the past few years have contributed to a better understanding of the use of trilostane in dogs. Trilostane is a competitive inhibitor of... (Review)
Review
Many articles published in the past few years have contributed to a better understanding of the use of trilostane in dogs. Trilostane is a competitive inhibitor of 3β-hydroxysteroid dehydrogenase, the enzyme essential for synthesis of cortisol and all other steroids. Trilostane is reported to be safe and effective in the treatment of pituitary-dependent hyperadrenocorticism (HAC), adrenal-dependent HAC, and alopecia X. While trilostane controls most of the clinical signs associated with HAC, abnormalities such as hypertension, hypercoagulability, and proteinuria may persist despite therapy. Because the duration of cortisol suppression after a dose of trilostane is often less than 12 hours, many dogs with HAC could benefit from low dose trilostane treatment every 12 hours. Many controversies regarding trilostane still exist. This review provides a comprehensive commentary on trilostane's indications, mode of action, dose, monitoring, efficacy, and adverse effects.
Topics: Adrenocortical Hyperfunction; Alopecia; Animals; Dihydrotestosterone; Dog Diseases; Dogs; Enzyme Inhibitors; Pituitary ACTH Hypersecretion
PubMed: 29606727
DOI: No ID Found -
Endocrine Reviews Jun 2017Benefits associated with lowered serum DHT levels after 5α-reductase inhibitor (5AR-I) therapy in men have contributed to a misconception that circulating DHT levels... (Review)
Review
Benefits associated with lowered serum DHT levels after 5α-reductase inhibitor (5AR-I) therapy in men have contributed to a misconception that circulating DHT levels are an important stimulus for androgenic action in target tissues (e.g., prostate). Yet evidence from clinical studies indicates that intracellular concentrations of androgens (particularly in androgen-sensitive tissues) are essentially independent of circulating levels. To assess the clinical significance of modest elevations in serum DHT and the DHT/testosterone (T) ratio observed in response to common T replacement therapy, a comprehensive review of the published literature was performed to identify relevant data. Although the primary focus of this review is about DHT in men, we also provide a brief overview of DHT in women. The available published data are limited by the lack of large, well-controlled studies of long duration that are sufficiently powered to expose subtle safety signals. Nonetheless, the preponderance of available clinical data indicates that modest elevations in circulating levels of DHT in response to androgen therapy should not be of concern in clinical practice. Elevated DHT has not been associated with increased risk of prostate disease (e.g., cancer or benign hyperplasia) nor does it appear to have any systemic effects on cardiovascular disease safety parameters (including increased risk of polycythemia) beyond those commonly observed with available T preparations. Well-controlled, long-term studies of transdermal DHT preparations have failed to identify safety signals unique to markedly elevated circulating DHT concentrations or signals materially different from T.
Topics: 5-alpha Reductase Inhibitors; Animals; Dihydrotestosterone; Female; Humans; Male; Prostate; Prostatic Neoplasms; Sex Characteristics; Testosterone
PubMed: 28472278
DOI: 10.1210/er.2016-1067 -
Journal of Biomedical Science Mar 2022Androgenetic alopecia (AGA) is a genetic disorder caused by dihydrotestosterone (DHT), accompanied by the senescence of androgen-sensitive dermal papilla cells (DPCs)...
BACKGROUND
Androgenetic alopecia (AGA) is a genetic disorder caused by dihydrotestosterone (DHT), accompanied by the senescence of androgen-sensitive dermal papilla cells (DPCs) located in the base of hair follicles. DHT causes DPC senescence in AGA through mitochondrial dysfunction. However, the mechanism of this pathogenesis remains unknown. In this study, we investigated the protective role of cyanidins on DHT-induced mitochondrial dysfunction and DPC senescence and the regulatory mechanism involved.
METHODS
DPCs were used to investigate the effect of DHT on mitochondrial dysfunction with MitoSOX and Rhod-2 staining. Senescence-associated β-galactosidase activity assay was performed to examine the involvement of membrane AR-mediated signaling in DHT-induced DPC senescence. AGA mice model was used to study the cyanidins on DHT-induced hair growth deceleration.
RESULTS
Cyanidin 3-O-arabinoside (C3A) effectively decreased DHT-induced mtROS accumulation in DPCs, and C3A reversed the DHT-induced DPC senescence. Excessive mitochondrial calcium accumulation was blocked by C3A. C3A inhibited p38-mediated voltage-dependent anion channel 1 (VDAC1) expression that contributes to mitochondria-associated ER membrane (MAM) formation and transfer of calcium via VDAC1-IP3R1 interactions. DHT-induced MAM formation resulted in increase of DPC senescence. In AGA mice models, C3A restored DHT-induced hair growth deceleration, which activated hair follicle stem cell proliferation.
CONCLUSIONS
C3A is a promising natural compound for AGA treatments against DHT-induced DPC senescence through reduction of MAM formation and mitochondrial dysfunction.
Topics: Animals; Anthocyanins; Cellular Senescence; Dihydrotestosterone; Hair Follicle; Mice; Mitochondria
PubMed: 35255899
DOI: 10.1186/s12929-022-00800-7 -
The Journal of Steroid Biochemistry and... Jun 2021Higher endogenous testosterone levels are associated with reduced chronic disease risk and mortality. Since the mid-20th century, there have been significant changes in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Higher endogenous testosterone levels are associated with reduced chronic disease risk and mortality. Since the mid-20th century, there have been significant changes in dietary patterns, and men's testosterone levels have declined in western countries. Cross-sectional studies show inconsistent associations between fat intake and testosterone in men.
METHODS
Studies eligible for inclusion were intervention studies, with minimal confounding variables, comparing the effect of low-fat vs high-fat diets on men's sex hormones. 9 databases were searched from their inception to October 2020, yielding 6 eligible studies, with a total of 206 participants. Random effects meta-analyses were performed using Cochrane's Review Manager software. Cochrane's risk of bias tool was used for quality assessment.
RESULTS
There were significant decreases in sex hormones on low-fat vs high-fat diets. Standardised mean differences with 95 % confidence intervals (CI) for outcomes were: total testosterone [-0.38 (95 % CI -0.75 to -0.01) P = 0.04]; free testosterone [-0.37 (95 % CI -0.63 to -0.11) P = 0.005]; urinary testosterone [-0.38 (CI 95 % -0.66 to -0.09) P = 0.009]; and dihydrotestosterone [-0.3 (CI 95 % -0.56 to -0.03) P = 0.03]. There were no significant differences for luteinising hormone or sex hormone binding globulin. Subgroup analysis for total testosterone, European and North American men, showed a stronger effect [-0.52 (95 % CI -0.75 to -0.3) P < 0.001].
CONCLUSIONS
Low-fat diets appear to decrease testosterone levels in men, but further randomised controlled trials are needed to confirm this effect. Men with European ancestry may experience a greater decrease in testosterone, in response to a low-fat diet.
Topics: Diet, Fat-Restricted; Diet, High-Fat; Dihydrotestosterone; Humans; Male; Sex Hormone-Binding Globulin; Testosterone
PubMed: 33741447
DOI: 10.1016/j.jsbmb.2021.105878 -
Journal of Veterinary Internal Medicine Nov 2021The use of adrenocorticotropic hormone stimulation test as method to monitor efficacy of trilostane treatment of hypercortisolism (HC) in dogs has been questioned.
BACKGROUND
The use of adrenocorticotropic hormone stimulation test as method to monitor efficacy of trilostane treatment of hypercortisolism (HC) in dogs has been questioned.
OBJECTIVES
To evaluate and compare 12 methods with which to monitor efficacy of trilostane treatment in dogs with HC.
ANIMALS
Forty-five client-owned dogs with HC treated with trilostane q12h.
METHODS
Prospective cross-sectional observational study. The dogs were categorized as well-controlled, undercontrolled, and unwell through a clinical score obtained from an owner questionnaire. The ability to correctly identify trilostane-treatment control of dogs with HC with the following variables was evaluated: before trilostane serum cortisol (prepill), before-ACTH serum cortisol, post-ACTH serum cortisol, plasma endogenous ACTH concentrations, prepill/eACTH ratio, serum haptoglobin (Hp) concentration, serum alanine aminotransferase (ALT), gamma-glutamyl transferase (γGT) and alkaline phosphatase activity, urine specific gravity, and urinary cortisol : creatinine ratio.
RESULTS
Ninety-four re-evaluations of 44 dogs were included; 5 re-evaluations of 5 unwell dogs were excluded. Haptoglobin was significantly associated with the clinical score (P < .001) and in the receiver operating characteristic analysis, Hp cutoff of 151 mg/dL correctly identified 90.0% of well-controlled dogs (specificity) and 65.6% of undercontrolled dogs (sensitivity). Alanine aminotransferase (P = .01) and γGT (P = .009) were significantly higher in undercontrolled dogs. Cutoff of ALT and γGT greater than or equal to 86 U/L and 5.8 U/L, respectively, were significantly associated with poor control of HC by trilostane.
CONCLUSIONS AND CLINICAL IMPORTANCE
Of all the 12 variables, Hp, and to a lesser degree ALT and γGT, could be considered additional tools to the clinical picture to identify well-controlled and undercontrolled trilostane-treated dogs.
Topics: Adrenocortical Hyperfunction; Animals; Cross-Sectional Studies; Cushing Syndrome; Dihydrotestosterone; Dog Diseases; Dogs; Enzyme Inhibitors; Hydrocortisone; Prospective Studies
PubMed: 34672018
DOI: 10.1111/jvim.16269 -
The Veterinary Record Dec 2016It is recommended that trilostane therapy of canine hyperadrenocorticism is monitored using an ACTH stimulation test, however this has never been validated. Three...
It is recommended that trilostane therapy of canine hyperadrenocorticism is monitored using an ACTH stimulation test, however this has never been validated. Three cortisol concentrations (pre-trilostane, 3-hour posttrilostane and 1-hour post-ACTH stimulation) were compared to a clinical score obtained from an owner questionnaire. There were 110 sets of 3 cortisol measurements and questionnaires obtained from 67 trilostane treated dogs. Questionnaire results were used to classify each dog as well or unwell. Well dogs were then categorised as having excellent, moderate or poor hyperadrenocorticism control, using thresholds produced by 14 independent veterinarians. Correlation co-efficients were used to compare the three cortisol concentrations to the owner score and the Kruskal Wallis and Mann-Whitney U tests were used to compare the three cortisol concentrations between categories of control. Cortisol cut-off values between significantly different categories were determined using ROC curves. Pre-trilostane and 3-hour post-trilostane cortisol were better correlated to the owner score and had cut-offs to differentiate between categories of control that had superior sensitivity and specificity results, than the post-ACTH cortisol. Iatrogenic hypoadrenocorticism was not detected in any unwell dog. This study shows that the pre-trilostane and 3-hour post-trilostane cortisol are potentially better monitoring methods than the ACTH stimulation test.
Topics: Adrenocortical Hyperfunction; Adrenocorticotropic Hormone; Animals; Diagnostic Techniques, Endocrine; Dihydrotestosterone; Dog Diseases; Dogs; Female; Hydrocortisone; Male; Prospective Studies; Reproducibility of Results; Surveys and Questionnaires
PubMed: 27803375
DOI: 10.1136/vr.103744 -
The Journal of Pathology Apr 2022Benign prostatic hyperplasia (BPH) is a progressive expansion of peri-urethral prostate tissue common in aging men. Patients with enlarged prostates are treated with...
Benign prostatic hyperplasia (BPH) is a progressive expansion of peri-urethral prostate tissue common in aging men. Patients with enlarged prostates are treated with 5-alpha reductase inhibitors (5ARIs) to shrink prostate volume by blocking the conversion of testosterone to dihydrotestosterone (DHT). A reduction in DHT levels can elicit atrophy and apoptosis of prostate secretory luminal cells, which results in a favorable clinical response characterized by improved lower urinary tract symptoms. However, the histologic response to 5ARI treatment is often heterogeneous across prostate acini and lower urinary tract symptoms can persist to require surgical intervention. We used two spatial profiling approaches to characterize gene expression changes across histologically normal and atrophied regions in prostates from 5ARI-treated men. Objective transcriptomic profiling using the Visium spatial gene expression platform showed that 5ARI-induced atrophy of prostate luminal cells correlated with reduced androgen receptor signaling and increased expression of urethral club cell genes including LTF, PIGR, OLFM4, SCGB1A1, and SCGB3A1. Prostate luminal cells within atrophied acini adapted to decreased DHT conditions by increasing NF-κB signaling and anti-apoptotic BCL2 expression, which may explain their survival. Using GeoMx digital spatial profiling with a probe set to assess ~18 000 RNA targets, we confirmed that atrophied acini expressing SCGB3A1 displayed higher levels of club cell markers compared with histologically normal acini with NKX3-1 expression. In addition, club-like cells within regions of 5ARI-induced atrophy closely resembled true club cells from the prostatic urethra. A comparison of histologically normal regions from 5ARI-treated men and histologically normal regions from untreated men revealed few transcriptional differences. Taken together, our results describe a heterogeneous response to 5ARI treatment where cells in atrophied acini undergo an adaptation from a prostate secretory luminal to a club cell-like state in response to 5ARI treatment. © 2021 The Pathological Society of Great Britain and Ireland.
Topics: 5-alpha Reductase Inhibitors; Atrophy; Dihydrotestosterone; Humans; Lower Urinary Tract Symptoms; Male; Prostate; Prostatic Hyperplasia
PubMed: 34928497
DOI: 10.1002/path.5857