Influence of Androgenic Status on the α2/β-Adrenergic Control of Lipolysis in White Fat Cells: Predominant α2-Antilipolytic Response in Testosterone-Treated-Castrated Hamsters*

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Abstract
The aim of this study was to evaluate the influence of castration with or without testosterone propionate (TP) administration (one daily injection of 1 mg for 10 days) on the fat cell lipolytic activity in male hamsters. Basal and maximal lipolytic responses to the pure .beta.-adrenergic agonist isoproterenol, the mixed .alpha.2- and .beta.-adrenergic agonist epinephrine, and the nonadrenergic compounds ACTH and 3-isobutyl-1-methylxanthine were all reduced by half in castrated animals. TP treatment restored these defective responses to control values, except the response to epinephrine which remained paradoxically unchanged. Sensitivity of lipolysis to epinephrine was unimpaired by castration but markedly reduced (10-fold) in TP-treated castrated hamsters. The antilipolytic potencies of the .alpha.2-component of epinephrine and of the two .alpha.2-agonists, UK 14304 and clonidine, were reduced by half in castrated animals, and returned to a value slightly higher than control after TP treatment. These changes in lipolysis were accompanied by parallel alterations in the stimulated cAMP responses to isoproterenol and forskolin but not to epinephrine. The latter was either unimpaired by castration or was clearly inhibited after TP treatment. Castration also induced a 2-fold decrease in the inhibitory potency of clonidine toward forskolin-stimulated cAMP production. Finally, these changes in the potency of clonidine were accompanied by parallel variations of the number of fat cell .alpha.2-adrenoreceptors. These results indicate that testosterone in vivo, while increasing the .beta.-adrenergic lipolytic action of catecholamines (possibly through enhancement of the adenylate cyclase activity), promotes, to a greater extent, their .alpha.2-adrenoceptor-mediated antilipolytic potency. By providing the first demonstration that the androgenic status controls the functional .alpha.2/.beta.-adrenergic balance of fat cells, this study also emphasizes the potential importance of such a control in the mechanisms underlying the sex-related differences in adipose tissue regional distribution and fat cell size.
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