-
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 -
Nihon Rinsho. Japanese Journal of... Dec 1999
Review
Topics: 3-Oxo-5-alpha-Steroid 4-Dehydrogenase; Dihydrotestosterone; Humans
PubMed: 10778118
DOI: No ID Found -
Journal of Andrology 1992Androgen action in sexual tissues, especially skin and the prostate, is expressed by dihydrotestosterone (DHT) acting at the nuclear level. Dihydrotestosterone in the... (Review)
Review
Androgen action in sexual tissues, especially skin and the prostate, is expressed by dihydrotestosterone (DHT) acting at the nuclear level. Dihydrotestosterone in the circulation and target tissues is almost solely derived from the peripheral conversion of secreted testosterone (T) in men and androstenedione in women. The general pathway is testosterone----DHT in equilibrium with androstanediol (3 alpha diol). However, a number of studies suggest that blood DHT or 3 alpha diol are not reliable indicators of peripheral DHT formation. This is particularly suggested by discrepancies in the specific activity of DHT in blood and urine following infusion of labeled DHT, suggesting that total body DHT formation is not reflected by blood levels. Thus, DHT should be thought of as a paracrine hormone formed and acting primarily in target tissues. 3 alpha androstanediol glucuronide (3 alpha diol G) is a major metabolite of DHT. An important site of its formation is the skin. Levels in blood and urine are increased in hirsutism and acne, and blood levels closely parallel pubertal development. 3 alpha diol G levels are especially increased in adrenal disorders of androgenicity such as andrenogenital syndrome; it is also a good marker of response to therapy. Levels are reduced in various forms of male pseudohermaphroditism. 3 alpha androstanediol glucuronide appears to be the best marker available of DHT formation in target tissues such as skin.
Topics: Dihydrotestosterone; Humans
PubMed: 1551803
DOI: No ID Found -
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 -
Annals of Medicine Jun 1993Male ageing coincides on average with progressive impairment of testicular function. The most striking plasma changes are an increase in sex hormone binding globulin... (Review)
Review
Male ageing coincides on average with progressive impairment of testicular function. The most striking plasma changes are an increase in sex hormone binding globulin (SHBG) and a decrease in non SHBG-bound testosterone, which is the only testosterone subfraction effectively bioavailable for target tissues. In healthy subjects the bioavailable testosterone declines by approximately 1% per year between 40 and 70 years but a more pronounced decline has been observed in non-healthy groups, especially in high cardiovascular risks groups. Relative androgen deficiency is likely to have unfavourable consequences on muscle, adipose tissue, bone, haematopoiesis, fibrinolysis, insulin sensitivity, central nervous system, mood and sexual function and might be treated by an appropriate androgen supplementation. The potential risk for prostate has been the main reason for limiting indications of such treatment. Testosterone (T) and dihydrotestosterone (DHT) are two potent androgens which have opposite effects regarding aromatase activity, an enzyme present in prostate stroma and suspected to have a pathogenic influence through local oestradiol synthesis. T is the main substrate for aromatase and oestradiol synthesis while DHT is not aromatizable and, at sufficient concentration, decreases T and oestradiol levels. A 1.8 years survey of 37 men aged 55-70 years treated with daily percutaneous DHT treatment suggested that high plasma levels of DHT (> 8.5 nmol/l) effectively induced clinical benefits while slightly but significantly reducing prostate size. Early stages of prostate hypertrophy require synergic stimulation by both DHT and oestradiol, and suppressing oestradiol instead of DHT seems easier and better adapted to the specific situation of aged hypogonadic men.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Administration, Cutaneous; Aged; Aging; Cardiovascular Diseases; Dihydrotestosterone; Humans; Male; Middle Aged; Prostate; Prostatic Hyperplasia; Testosterone
PubMed: 7687444
DOI: 10.3109/07853899309147869 -
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 Prostate. Supplement 1996Androgen action differs from that of most hormones in the testosterone, the major androgen secreted from the testes and the most abundant androgen in the circulation of... (Review)
Review
Androgen action differs from that of most hormones in the testosterone, the major androgen secreted from the testes and the most abundant androgen in the circulation of men, is not the principal androgen within target cells. Indeed, abundant evidence indicates that most androgen actions are mediated by the 5alpha-reduced metabolite dihydrotestosterone that is formed in target tissues. The conversion of testosterone to dihydrotestosterone is mediated by two isoenzymes; mutations in the steroid 5alpha-reductase 2 gene cause a rare autosomal-recessive form of male pseudohermaphroditism, and inhibition of this enzyme causes regression of the prostate gland. Dihydrotestosterone binds more tightly to the androgen receptor that does testosterone, but it is not clear whether this property is the sole explanation for its essential role in androgen action. Nor is it clear whether some androgenic effects may be mediated by circulating dihydrotestosterone acting as a hormone.
Topics: Androgens; Animals; Cholestenone 5 alpha-Reductase; Dihydrotestosterone; Humans; Male; Oxidoreductases; Prostatic Hyperplasia
PubMed: 8630237
DOI: No ID Found -
The Ocular Surface Apr 2020We discovered that dihydrotestosterone (DHT) decreases the ability of lipopolysaccharide, a bacterial toxin, to stimulate the secretion of leukotriene B4, a potent...
PURPOSE
We discovered that dihydrotestosterone (DHT) decreases the ability of lipopolysaccharide, a bacterial toxin, to stimulate the secretion of leukotriene B4, a potent proinflammatory mediator, by immortalized human meibomian gland epithelial cells (IHMGECs). We hypothesize that this hormone action reflects an androgen suppression of proinflammatory gene activity in these cells. Our goal was to test this hypothesis. For comparison, we also examined whether DHT treatment elicits the same effect in immortalized human corneal (IHC) and conjunctival (IHConj) ECs.
METHODS
Differentiated cells were cultured in media containing vehicle or 10 nM DHT. Cells (n = 3 wells/treatment group) were then processed for RNA isolation and the analysis of gene expression by using Illumina BeadChips, background subtraction, cubic spline normalization and Geospiza software.
RESULTS
Our results demonstrate that DHT significantly suppressed the expression of numerous immune-related genes in HMGECs, such as those associated with antigen processing and presentation, innate and adaptive immune responses, chemotaxis, and cytokine production. DHT also enhanced the expression of genes for defensin β1, IL-1 receptor antagonist, and the anti-inflammatory serine peptidase inhibitor, Kazal type 5. In contrast, DHT had no effect on proinflammatory gene expression in HCECs, and significantly increased 33 gene ontologies linked to the immune system in HConjECs.
CONCLUSIONS
Our findings support our hypothesis that androgens suppress proinflammatory gene expression in IHMGECs. This hormone effect may contribute to the typical absence of inflammation within the human meibomian gland.
Topics: Cells, Cultured; Dihydrotestosterone; Epithelial Cells; Gene Expression; Humans; Meibomian Glands
PubMed: 32112874
DOI: 10.1016/j.jtos.2020.02.006 -
Bailliere's Clinical Endocrinology and... Oct 1998Testosterone therapy is commonly used to treat male hypogonadism, androgen deficiency of severe illness, androgen deficiency of ageing and microphallus in infancy. The... (Review)
Review
Testosterone therapy is commonly used to treat male hypogonadism, androgen deficiency of severe illness, androgen deficiency of ageing and microphallus in infancy. The effects of testosterone are mediated directly as testosterone or after conversion to either dihydrotestosterone (DHT) or oestradiol. DHT is a potent androgen and cannot be aromatized to oestrogens, therefore acting as a pure androgen. DHT has been proposed as an androgen replacement therapy, with possible advantages over testosterone in certain circumstances in the ageing population as well as in patients with gynaecomastia and microphallus. A potential advantage of DHT over testosterone as an androgen replacement therapy is the reported and seemingly paradoxically muted effects of DHT on prostate growth. The decreased effect of DHT compared with testosterone on the prostate gland of humans may be due to the decrease in intraprostatic oestradiol levels. The potential beneficial effect of less prostate growth after DHT requires substantiation and, if true, must be balanced against any negative effects that might occur on bone, lipids and sexuality when a pure androgen replaces treatment with an aromatizable androgen.
Topics: 3-Oxo-5-alpha-Steroid 4-Dehydrogenase; Aged; Aging; Dihydrotestosterone; Gels; Hormone Replacement Therapy; Humans; Hypogonadism; Male; Middle Aged
PubMed: 10332569
DOI: 10.1016/s0950-351x(98)80267-x -
Andrologia Dec 20075alpha-Dihydrotestosterone (DHT), the most powerful naturally occurring androgen, is commercially available since 1982 as a gel. In view of its considerably higher... (Review)
Review
5alpha-Dihydrotestosterone (DHT), the most powerful naturally occurring androgen, is commercially available since 1982 as a gel. In view of its considerably higher biopotency (three to six times) than of testosterone, side effects, particularly on the main target organ of androgens, the prostate, are anticipated. In fact, DHT appears to be a prostate-sparing androgen for two reasons. Unlike testosterone, it does not undergo any further amplification in biopotency through 5alpha reduction in the prostate. Secondly, it is likely to lead to less aromatisation of testosterone to oestradiol in the prostate, thus reducing local oestradiol concentrations. Oestrogens have been implicated in the aetiology of benign prostate hyperplasia and prostate cancer. However, aromatisation of testosterone has appeared to be essential for the maintenance of bone mineral density. Administration of DHT reduces circulating oestradiol levels, but the levels remain above the levels critical for the antiresorptive effect of oestrogens on bone. Effects of DHT on erythropoiesis and on lipids are very similar to those of testosterone. Safety concerns regarding androgen treatment with DHT are similar to those of treatment with testosterone, while the effects of DHT on the prostate are likely to be less biopotent.
Topics: Bone and Bones; Cardiovascular System; Dihydrotestosterone; Erythropoiesis; Estradiol; Humans; Lipids; Male; Prostate
PubMed: 18076420
DOI: 10.1111/j.1439-0272.2007.00786.x