Abel Brent S, Muniyappa Ranganath, Stratton Pamela, Skarulis Monica C, Gorden Phillip, Brown Rebecca J
Diabetes, Endocrinology and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Bethesda, Md., USA.
Neuroendocrinology. 2016;103(3-4):402-7. doi: 10.1159/000439432. Epub 2015 Aug 25.
Leptin replacement in patients with leptin gene mutations improves hypogonadotropic hypogonadism. The effects of leptin replacement on luteinizing hormone (LH) secretion in patients with lipodystrophy are unknown.
We examined nocturnal LH secretory dynamics on and off exogenous leptin therapy using a 2-period, nonrandomized study that included leptin-naïve and leptin-treated subjects with lipodystrophy.
In period 1 (5 days) the leptin-treated group (n = 4) continued leptin; leptin was then withdrawn for the next 14 days (period 2). Leptin-naïve subjects (n = 8) were studied without leptin in period 1 and with leptin replacement in period 2. LH secretory dynamics were assessed (23:00-07:00 h, sampling every 10 min, analyzed by multiparameter deconvolution algorithm) at the end of each period.
Mean (on vs. off: 5.0 ± 3.1 vs. 3.2 ± 1.3 IU/l, p = 0.04) and integrated LH concentrations (2,403 ± 1,495 vs. 1,534 ± 642 IU × l-1 × min-1, p = 0.04) were higher on leptin therapy. Leptin treatment increased burst mass (9.7± 15.4 vs. 7.0 ± 11.2 IU/l, p = 0.03) and tended to nonsignificantly increase LH burst frequency (0.77 ± 0.26 vs. 0.67 ± 0.24 h-1, p = 0.08). Consequently, leptin therapy increased the pulsatile production rate (64 ± 101 vs. 57 ± 73 IU × l-1 × 8 h-1, p = 0.01). On leptin, testosterone (507 ± 286 vs. 360 ± 174 ng/dl, p = 0.09) and estradiol levels (74 ± 36 vs. 29 ± 24 pg/ml, p = 0.01) were higher in males and females, respectively.
Leptin increases spontaneous nocturnal LH secretion in patients with lipodystrophy. This is consistent with rodent and in vitro studies showing a direct stimulatory effect (hypothalamic, pituitary or both) of leptin on LH secretion. These novel findings may explicate some of the salutary effects of leptin therapy on the hypothalamic-pituitary-gonadal axis in lipodystrophy.
给瘦素基因突变患者补充瘦素可改善低促性腺激素性性腺功能减退。瘦素替代疗法对脂肪营养不良患者促黄体生成素（LH）分泌的影响尚不清楚。
我们采用一项为期2个阶段的非随机研究，对未接受过瘦素治疗和接受过瘦素治疗的脂肪营养不良患者进行研究，观察夜间LH分泌动力学在接受和停用外源性瘦素治疗时的变化。
在第1阶段（5天），接受瘦素治疗的组（n = 4）继续使用瘦素；然后在接下来的14天（第2阶段）停用瘦素。未接受过瘦素治疗的受试者（n = 8）在第1阶段不使用瘦素，在第2阶段接受瘦素替代治疗。在每个阶段结束时评估LH分泌动力学（23:00 - 07:00时，每10分钟采样一次，通过多参数反卷积算法分析）。
接受瘦素治疗时LH的平均浓度（使用与停用：5.0±3.1 vs. 3.2±1.3 IU/l，p = 0.04）和积分浓度（2,403±1,495 vs. 1,534±642 IU×l⁻¹×min⁻¹，p = 0.04）更高。瘦素治疗增加了脉冲量（9.7±15.4 vs. 7.0±11.2 IU/l，p = 0.03）且有增加LH脉冲频率的趋势但无统计学意义（0.77±0.26 vs. 0.67±0.24 h⁻¹，p = 0.08）。因此，瘦素治疗增加了脉冲产生率（64±101 vs. 57±73 IU×l⁻¹×8 h⁻¹，p = 0.01）。接受瘦素治疗时，男性的睾酮水平（507±286 vs. 360±174 ng/dl，p = 0.09）和女性的雌二醇水平（74±36 vs. 29±24 pg/ml，p = 0.01）更高。
瘦素可增加脂肪营养不良患者夜间自发性LH分泌。这与啮齿动物和体外研究结果一致，这些研究表明瘦素对LH分泌有直接刺激作用（下丘脑、垂体或两者均有）。这些新发现可能解释了瘦素治疗对脂肪营养不良患者下丘脑 - 垂体 - 性腺轴的一些有益作用。
