Leptin and androgens in male obesity: Evidence for leptin contribution to reduced androgen levels
Leptin and androgens in male obesity: Evidence for leptin contribution to reduced androgen levels
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DOI：
10.1210/jc.84.10.3673
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发表时间：
1999-10-01
影响因子：
5.8
通讯作者：
Fabbri, A
中科院分区：
文献类型：
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作者：
Isidori, AM;Caprio, M;Fabbri, A
瘦素在血浆中的循环浓度与脂肪储备量相当。在肥胖男性中，雄激素水平与肥胖程度成比例地下降。最近，我们已经证明，在啮齿动物间质细胞中，瘦素通过功能性瘦素受体异构体抑制hcg刺激的睾酮(T)产生；其他人则发现瘦素抑制成年大鼠睾丸基底和hcg诱导的T分泌。在这项研究中，我们进一步研究了瘦素和男性雄激素之间的关系。研究了一大批从正常体重到极度肥胖（体重指数21.8-55.7）的男性的基础和hcg刺激的瘦素和性激素水平。初步横断面研究显示，循环瘦素和脂肪量（FM）与总T和游离T呈负相关（r = -0.51和r = -0.38, P < 0.01和P < 0.05）。多元回归分析表明，在控制SHBG和/或LH和/或雌二醇（E-2）水平后，瘦素或Fbi与T之间的相关性并没有消失，瘦素是肥胖患者雄激素水平较低的最佳激素预测因子。动态研究表明，肥胖男性对LH/hCG刺激（5000 IU im）的T和游离T曲线下面积比对照组低30-40%，且与瘦素水平呈负相关（r = -0.45和r = -0.40，分别P < 0.01和P < 0.05）。此外，LH/ hcg刺激导致肥胖男性的17- oh孕酮与T比值高于对照组，而两组之间刺激的E-2水平或E-2/T比值均无差异。在所有受试者中，17- oh孕酮与T比值较基线增加的百分比与瘦素水平或FM直接相关（r = 0.40和r = 0.45, P < 0.01），但与E-2或其他激素变量无关。总之，我们的研究，以及之前的体外研究结果表明，过量的循环瘦素可能是男性肥胖中雄激素减少的重要因素。
Leptin circulates in plasma at concentrations that parallel the amount of fat reserves. In obese males, androgen levels decline in proportion to the degree of obesity. Recently, we have shown that in rodent Leydig cells leptin inhibits hCG-stimulated testosterone (T) production via a functional leptin receptor isoform; others have found that leptin inhibits basal and hCG-induced T secretion by testis from adult rats. In this study, we further investigated the relationship linking leptin and androgens in men. Basal and hCG-stimulated leptin and sex hormone levels were studied in a large group of men ranging from normal weight to very obese (body mass index, 21.8-55.7). Initial cross-sectional studies showed that circulating leptin and fat mass (FM) were inversely related with total and free T (r = -0.51 and r = -0.38, P < 0.01 and P < 0.05, respectively). Multiple regression analysis indicated that the correlation between leptin or Fbi and T was not lost after controlling for SHBG and/or LH and/or estradiol (E-2) levels and that leptin was the best hormonal predictor of the lower androgen levels in obesity. Dynamic studies showed that in obese men the area under the curve of T and free T to LH/hCG stimulation (5000 IU im) was 30-40% lower than in controls and inversely correlated with leptin levels (r = -0.45 and r = -0.40, P < 0.01 and P < 0.05, respectively). Also, LH/hCG-stimulation caused higher increases in 17-OH-progesterone to T ratio in obese men than in controls, whereas no differences were observed between groups either in stimulated E-2 levels or in the E-2/T ratio. In all subjects, the percentage increases from baseline in the 17-OH-progesterone to T ratio were directly correlated with leptin levels or FM (r = 0.40 and r = 0.45, P < 0.01), but not with E-2 or other hormonal variables. In conclusion, our studies, together with previous in vitro findings, indicate that excess of circulating leptin may be an important contributor to the development of reduced androgens in male obesity.