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Androgen Metabolism (androgen + metabolism)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Role of insulin, insulin-like growth factor-1, hyperglycaemic food and milk consumption in the pathogenesis of acne vulgaris

EXPERIMENTAL DERMATOLOGY, Issue 10 2009
Bodo C. Melnik
Abstract:, It is the purpose of this viewpoint article to delineate the regulatory network of growth hormone (GH), insulin, and insulin-like growth factor-1 (IGF-1) signalling during puberty, associated hormonal changes in adrenal and gonadal androgen metabolism, and the impact of dietary factors and smoking involved in the pathogenesis of acne. The key regulator IGF-1 rises during puberty by the action of increased GH secretion and correlates well with the clinical course of acne. In acne patients, associations between serum levels of IGF-1, dehydroepiandrosterone sulphate, dihydrotestosterone, acne lesion counts and facial sebum secretion rate have been reported. IGF-1 stimulates 5,-reductase, adrenal and gonadal androgen synthesis, androgen receptor signal transduction, sebocyte proliferation and lipogenesis. Milk consumption results in a significant increase in insulin and IGF-1 serum levels comparable with high glycaemic food. Insulin induces hepatic IGF-1 secretion, and both hormones amplify the stimulatory effect of GH on sebocytes and augment mitogenic downstream signalling pathways of insulin receptors, IGF-1 receptor and fibroblast growth factor receptor-2b. Acne is proposed to be an IGF-1-mediated disease, modified by diets and smoking increasing insulin/IGF1-signalling. Metformin treatment, and diets low in milk protein content and glycaemic index reduce increased IGF-1 signalling. Persistent acne in adulthood with high IGF-1 levels may be considered as an indicator for increased risk of cancer, which may require appropriate dietary intervention as well as treatment with insulin-sensitizing agents. [source]

Androgen action on human skin , from basic research to clinical significance

EXPERIMENTAL DERMATOLOGY, Issue 2004
Christos C. Zouboulis
Abstract:, Androgens affect several functions of the human skin, such as sebaceous gland growth and differentiation, hair growth, epidermal barrier homeostasis and wound healing. Their effects are mediated by binding to nuclear androgen receptors. Androgen activation and deactivation are mainly intracellular events. They differ from cell type to cell type and between cells at different locations. The major circulating androgens, dehydroepiandrosterone sulfate and androstenedione, are predominantly produced in the adrenal glands, and testosterone and 5,-dihydrotestosterone are mainly synthesized in the gonads. Testosterone in women and 5,-dihydrotestosterone in both genders are also synthesized in the skin. Skin cells express all androgen metabolizing enzymes required for the independent cutaneous synthesis of androgens and the development of hyperandrogenism-associated conditions and diseases, such as seborrhea, acne, hirsutism and androgenetic alopecia. The major thrust of drug design for the treatment of androgen-associated disorders has been directed against several levels of androgen function and metabolism. Partial effectiveness has only been achieved either by androgen depletion, inhibition of androgen metabolism or blockade of the androgen receptor. [source]

Gender-incompatible liver transplantation is not a risk factor for patient survival

LIVER INTERNATIONAL, Issue 2 2009
Frank Lehner
Abstract Background/Aims: Clinical data may be suggestive for differences in patient survival in gender-incompatible orthotopic liver transplantation (OLT), but findings are inconsistent and are putatively linked to circulating hormones. We therefore investigated patient survival as well as metabolism of steroids to identify possible causes of improved graft survival in gender-mismatched OLT. Methods: We examined our single-centre database of 1355 recipients of first liver transplants for overall patient survival by non-parametric and parametric analysis of multivariance taking the age of recipient and donor, ischaemia time, underlying liver disease and the time period of transplantation into account. Furthermore, the metabolism of androgens in gender-incompatible OLT was studied in cultures of primary human hepatocytes obtained from male and female patients. Results: Unlike previous studies we were unable to determine overall significant differences in patient survival in gender-incompatible OLT, even though a statistically significant improved patient survival was observed when male donor livers were transplanted into female recipients in univariant analysis (P=0.047). However, when the overall patient management was taken into account no difference in survival was determined in multivariant analysis. Importantly, the metabolism of testosterone did not differ between male and female hepatocyte cultures, except for the production of 6-,-hydroxy-testosterone (P<0.001). Conclusions: Taken collectively, clinical observations may tend to suggest a slightly improved patient survival in gender-incompatible OLT but this cannot be explained on the bases of androgen metabolism. Overall, we view gender-incompatible liver transplantation not to be a confounder in patient survival after OLT. [source]

Estrogen signaling and disruption of androgen metabolism in acquired androgen-independence during cadmium carcinogenesis in human prostate epithelial cells

THE PROSTATE, Issue 2 2007
Lamia Benbrahim-Tallaa
Abstract BACKGROUND Lethal prostate cancers often become androgen-independent due to androgen receptor (AR) overexpression. The role of cadmium in prostate tumor progression was determined. METHODS Control and cadmium-transformed prostate epithelial cells (CTPE) were compared for steroid-induced proliferation, steroid receptor expression, and androgen metabolism. RESULTS CTPE cells showed rapid proliferation in complete medium and sustained proliferation in steroid-reduced medium. Androgens stimulated significantly less cell proliferation and AR-related genes expression in CTPE cells. 5,-Dihydrotestosterone increased PSA expression more effectively in control cells. Flutamide reduced 5,-dihydrotestosterone-stimulated growth less effectively in CTPE cells compared to control. CTPE cells showed decreased p27 expression. Estrogen receptors were overexpressed and estradiol markedly stimulated proliferation in CTPE cells. In CTPE cells 5,-aromatase was markedly increased, while 5,-reductase was decreased. CONCLUSIONS Cadmium-induced malignant transformation stimulates androgen independence, unrelated to AR expression or activity. Increased estrogen receptor and 5,-aromatase expression suggest estrogen signaling may be critical to this process. Prostate © 2006 Wiley-Liss, Inc. [source]