Pecquery R, Leneveu M C, Giudicelli Y
Department of Biochemistry, Faculty of Medicine Paris-Quest, Centre Hospitalier de Poissy, France.
Endocrinology. 1988 Jun;122(6):2590-6. doi: 10.1210/endo-122-6-2590.
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-adrenoreceptor-mediated antilipolytic potency. By providing the first demonstration that the androgenic status controls the functional alpha 2/beta-adrenergic balance in 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.
本研究的目的是评估去势以及去势后给予丙酸睾酮（TP）（每日注射1 mg，共10天）对雄性仓鼠脂肪细胞脂解活性的影响。去势动物对纯β-肾上腺素能激动剂异丙肾上腺素、α2和β-肾上腺素能混合激动剂肾上腺素以及非肾上腺素能化合物促肾上腺皮质激素（ACTH）和3-异丁基-1-甲基黄嘌呤的基础脂解反应和最大脂解反应均降低了一半。TP治疗可将这些缺陷反应恢复至对照值，但对肾上腺素的反应仍反常地未改变。脂解对肾上腺素的敏感性在去势后未受损害，但在接受TP治疗的去势仓鼠中显著降低（10倍）。肾上腺素的α2成分以及两种α2激动剂UK 14304和可乐定的抗脂解效力在去势动物中降低了一半，TP治疗后恢复至略高于对照的值。这些脂解变化伴随着对异丙肾上腺素和福斯高林刺激的cAMP反应的平行改变，但对肾上腺素的反应未改变。后者在去势后未受损害或在TP治疗后明显受到抑制。去势还导致可乐定对福斯高林刺激的cAMP产生的抑制效力降低了2倍。最后，可乐定效力的这些变化伴随着脂肪细胞α2肾上腺素能受体数量的平行变化。这些结果表明，体内睾酮在增加儿茶酚胺的β-肾上腺素能脂解作用（可能通过增强腺苷酸环化酶活性）的同时，在更大程度上促进了它们由α2肾上腺素能受体介导的抗脂解效力。本研究首次证明雄激素状态控制脂肪细胞中功能性α2/β-肾上腺素能平衡，也强调了这种控制在脂肪组织区域分布和脂肪细胞大小性别相关差异潜在机制中的重要性。
