The role of non-aromatizable testosterone metabolite in metabolic pathways.
DuÅ¡ková M, PospÃÅ¡ilová H.
Source
Institute of Endocrinology, Prague, Czech Republic.
mduskova@endo.cz
Abstract
Dihydrotestosterone (DHT) originates via irreversible reduction of testosterone by catalytic activity of 5alpha-reductase enzyme and it is demonstratively the most effective androgen. Androgens influence adipose tissue in men either directly by stimulation of the androgen receptor or indirectly, after aromatization, by acting at the estrogen receptor. DHT as a non-aromatizable androgen could be responsible for a male type fat distribution. The theory of non-aromatizable androgens as a potential cause of a male type obesity development has been studied intensively. However, physiological levels of DHT inhibit growth of mature adipocytes. In animal models, substitution of DHT in males after gonadectomy has a positive effect on body composition as a testosterone therapy. Thus, DHT within physiological range positively influences body composition. However, there are pathological conditions with an abundance of DHT, e.g. androgenic alopecia and benign prostatic hyperplasia. These diseases are considered as risk factors for development of metabolic syndrome or atherosclerosis. In obese people, DHT metabolism in adipose tissue is altered. Local abundance of non-aromatizable androgen has a negative effect on adipose tissue and it could be involved in pathogenesis of metabolic and cardiovascular diseases. Increased DHT levels, compared to physiological levels, have negative effect on development of cardiovascular diseases. Difference between the effect of physiological and increased level brings about certain paradox.
Hair growth stimulated by conditioned medium of adipose-derived stem cells is enhanced by hypoxia: evidence of increased growth factor secretion.
Park BS, Kim WS, Choi JS, Kim HK, Won JH, Ohkubo F, Fukuoka H.
Source
Leaders Clinic, Seoul, Korea.
Abstract
Adipose-derived stem cells (ADSCs) and their secretomes mediate diverse skin-regeneration effects, such as wound-healing and antioxidant protection, that are enhanced by hypoxia. We investigated the hair-growth-promoting effect of conditioned medium (CM) of ADSCs to determine if ADSCs and their secretomes regenerate hair and if hypoxia enhances hair regeneration. If so, we wanted to identify the factors responsible for hypoxia-enhanced hair-regeneration. We found that ADSC-CM administrated subcutaneously induced the anagen phase and increased hair regeneration in C(3)H/NeH mice. In addition, ADSC-CM increased the proliferation of human follicle dermal papilla cells (HFDPCs) and human epithelial keratinocytes (HEKs), which are derived from two major cell types present in hair follicles. We investigated the effect of hypoxia on ADSC function using the same animal model in which hypoxia increased hair regrowth. Forty-one growth factors in ADSC-CM from cells cultured under hypoxic or normoxic conditions were analyzed. The secretion of insulin-like growth factor binding protein (IGFBP)-1, IGFBP-2, macrophage colony-stimulating factor (M-CSF), M-CSF receptor, platelet-derived growth factor receptor-beta, and vascular endothelial growth factor was significantly increased by hypoxia, while the secretion of epithelial growth factor production was decreased. It is reasonable to conclude that ADSCs promote hair growth via a paracrine mechanism that is enhanced by hypoxia.
Can J Physiol Pharmacol. 2011 Jun;89(6):383-91. Epub 2011 Jul 13.
Subcutaneous adipose tissue metabolism and pharmacology: a new investigative technique.
Martin E, Brassard P, Gagnon-Auger M, Yale P, Carpentier AC, Ardilouze JL.
Source
Diabetes and Metabolism Research Group, Division of Endocrinology, Department of Medicine, Sherbrooke University Hospital Centre, Sherbrooke, QC J1H 5N4, Canada.
Abstract
According to the Fick principle, any metabolic or hormonal exchange through a given tissue depends on the product of blood flow by arteriovenous difference. Because adipose tissue plays dual storage and endocrine roles, regulation of adipose tissue blood flow (ATBF) is of pivotal importance. Monitoring ATBF in humans can be achieved through different methodologies, such as the (133)Xe washout technique, considered to be the "gold standard", as well as microdialysis and other methods that are not well validated as of yet. This report describes a new method, called "adipose tissue microinfusion" or "ATM", which simultaneously quantifies ATBF by combining the (133)Xe washout technique together with variations of ATBF induced by local infusion of vasoactive agents. The most appropriate site for ATM investigation is the subcutaneous adipose tissue of the anterior abdominal wall. This innovative method conveniently enables the direct comparison of the effects on ATBF of any vasoactive compound, drug, or hormone against a contralateral saline control. The ATM method improves the accuracy and feasibility of physiological and pharmacological studies on the regulation of ATBF in vivo in humans.