The effects of androgens on the regulation of lipolysis in adipose precursor cells.
Adipose precursor cells from male rats were exposed in primary culture to testosterone (T) or dihydrotestosterone (DHT), and their effects on the regulation of lipolysis were studied. T, but not DHT, stimulated catecholamine-induced lipolysis in a dose-dependent manner, including physiological concentrations. The effect was equally pronounced with isoproterenol (a pure beta-adrenergic agonist) and norepinephrine (a mixed alpha 2- and beta-adrenergic agonist). The higher lipolytic capacity of catecholamines on T-treated cells was paralleled by a similar increase in the number of beta-adrenoceptors in the cells, without a change in the receptor affinity, suggesting that T induced new synthesis or externalization of beta-adrenoceptors. Both T and DHT stimulated forskolin-induced lipolysis, suggesting an androgen effect at the level of the catalytic subunit of adenylate cyclase. The pertussis toxin-stimulated lipolysis was not influenced by the presence of androgens in the culture medium, and no effect was seen on the antilipolytic effect of insulin. These effects did not disappear in the presence of an aromatase inhibitor, suggesting that the T effects were not mediated by conversion to estrogens. These cells showed specific saturable binding for androgens, with a Kd in the range of androgen concentrations shown to be active. In conclusion, androgens enhance the lipolytic capacity of these cells by increasing the apparent number of beta-adrenoceptors (T only) and the activity of adenylate cyclase (both T and DHT). These changes are not mediated by conversion to estrogens. These effects probably occur via binding to specific androgen receptors.
Xu
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Wallenberg Laboratory, Sahlgren's Hospital, University of Goteborg, Sweden.
De Pergola
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Björntorp
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D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D013196:Dihydrotestosterone / Q000494:pharmacology*; D005990:Glycerol / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D015741:Metribolone / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism*; D013739:Testosterone / Q000494:pharmacology*
D007328:Insulin; D011943:Receptors, Adrenergic, beta; D013196:Dihydrotestosterone; D005576:Colforsin; D015741:Metribolone; D013739:Testosterone; D007545:Isoproterenol; D005990:Glycerol; D009638:Norepinephrine