Pitteloud Nelly, Hardin Megan, Dwyer Andrew A, Valassi Elena, Yialamas Maria, Elahi Dariush, Hayes Frances J
Reproductive Endocrine Unit, BHX 511, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts 02114, USA.
J Clin Endocrinol Metab. 2005 May;90(5):2636-41. doi: 10.1210/jc.2004-2190. Epub 2005 Feb 15.
Insulin resistance is associated with low testosterone (T) levels in men, the mechanism of which is unclear. Thus, the aim of this study was to evaluate the hypothalamic-pituitary-gonadal axis in men with a spectrum of insulin sensitivity. Twenty-one men (aged 25-65 yr) had a glucose tolerance test and assessment of insulin sensitivity using a hyperinsulinemic-euglycemic clamp. Insulin sensitivity, expressed as the M value (milligrams per kilograms(-1) per minute(-1)), was calculated from the glucose disposal rate during the final 30 min of the clamp. Eighteen subjects had blood sampling every 10 min for 12 h to assess LH pulsatility. Hypogonadism was then induced with a GnRH antagonist, followed by sequential stimulation testing with GnRH (750 ng/kg, iv) and human chorionic gonadotropin (hCG; 1000 IU, im) to assess pituitary and testicular responsiveness, respectively. Nine subjects had normal glucose tolerance, nine had impaired glucose tolerance, and three had diabetes mellitus. There was a positive relationship between M and T levels (r = 0.46; P < 0.05). No relationship was seen between M and parameters of LH secretion, including mean LH levels, LH pulse amplitude, LH pulse frequency, and LH response to exogenous GnRH administration. In contrast, a strong correlation was observed between M and the T response to hCG (r = 0.73; P < 0.005). Baseline T levels correlated with the increase in T after hCG administration (r = 0.47; P < 0.05). During the clamp, T levels increased from a baseline level of 367 +/- 30 to 419 +/- 38 ng/dl during the last 30 min (P < 0.05). From these data we conclude that insulin resistance is associated with a decrease in Leydig cell T secretion in men. Additional studies are required to determine the mechanism of this effect.
胰岛素抵抗与男性低睾酮（T）水平相关，但其机制尚不清楚。因此，本研究旨在评估不同胰岛素敏感性男性的下丘脑-垂体-性腺轴。21名男性（年龄25 - 65岁）进行了葡萄糖耐量试验，并使用高胰岛素-正葡萄糖钳夹技术评估胰岛素敏感性。胰岛素敏感性以M值（毫克每千克⁻¹每分钟⁻¹）表示，根据钳夹最后30分钟的葡萄糖处置率计算得出。18名受试者每10分钟采血一次，共12小时，以评估促黄体生成素（LH）的脉冲性。然后用促性腺激素释放激素（GnRH）拮抗剂诱导性腺功能减退，接着分别用GnRH（750 ng/kg，静脉注射）和人绒毛膜促性腺激素（hCG；1000 IU，肌肉注射）进行序贯刺激试验，以评估垂体和睾丸的反应性。9名受试者葡萄糖耐量正常，9名葡萄糖耐量受损，3名患有糖尿病。M与T水平之间存在正相关（r = 0.46；P < 0.05）。未发现M与LH分泌参数之间存在相关性，包括平均LH水平、LH脉冲幅度、LH脉冲频率以及LH对外源性GnRH给药的反应。相反，观察到M与T对hCG的反应之间存在强烈相关性（r = 0.73；P < 0.005）。基线T水平与hCG给药后T的升高相关（r = 0.47；P < 0.05）。在钳夹过程中，T水平从基线水平367 ± 30 ng/dl在最后30分钟增加到419 ± 38 ng/dl（P < 0.05）。根据这些数据我们得出结论，胰岛素抵抗与男性睾丸间质细胞T分泌减少有关。需要进一步研究来确定这种作用的机制。
