Immunoreactive and bioactive luteinizing hormone in pubertal patients with chronic renal failure. Cooperative Study Group on Pubertal Development in Chronic Renal Failure.
Immunoreactive and bioactive luteinizing hormone in pubertal patients with chronic renal failure. Cooperative Study Group on Pubertal Development in Chronic Renal Failure.
复制标题
患有慢性肾功能衰竭的青春期患者的免疫反应性和生物活性黄体生成激素。
DOI：
10.1038/ki.1994.191
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发表时间：
1994
影响因子：
19.6
通讯作者：
Schärer,K
中科院分区：
文献类型：
--
作者：
Schaefer,F;Veldhuis,JD;Robertson,WR;Dunger,D;Schärer,K
青春期慢性肾功能衰竭患者的免疫反应性和生物活性促黄体生成素。LH脉冲性分泌紊乱被认为在慢性肾功能衰竭（CRF）患者青春期延迟和生殖功能紊乱的病因学中起作用，但从血浆浓度测量结果解释促性腺激素分泌受到激素代谢清除率改变的混淆。为了同时研究儿童LH分泌和清除，我们对36例不同程度CRF的青春期患者（18例男孩）和10例性别和青春期阶段相匹配的健康对照者的11小时过夜血清LH浓度-生物活性（bio-LH）和免疫反应性（i-LH）激素时间序列进行了多参数反卷积分析。12例晚期代偿期CRF患者接受保守治疗，12例接受透析治疗，12例在肾移植成功后接受研究。我们注意到：（1）与对照组（59 ± 28和63 ± 21 min）相比，透析组（155 ± 47和201 ± 31 min）和保守治疗组（148 ± 45和135 ± 70 min）的bio-LH和i-LH的平均（±se）血浆半衰期增加（均P < 0.05）。保守治疗组和肾移植术后患者血浆bio-LH半衰期与肾小球滤过率（GFR）呈负相关（r = -0.70; P < 0.0001）。(2)脉冲式生物LH产生率受青春期阶段（P = 0.018）和治疗状态（P = 0.017）的独立影响，在青春期阶段增加，透析患者（20 ± 4 IU/L * 11小时）和保守治疗患者（28 ± 9）显著低于对照组（43 ± 9;所有P < 0.05）。在保守治疗或移植后患者中，观察到脉动生物LH产生率与患者的生物LH产生率呈显著正相关（r = 0.53; P < 0.008）。i-LH脉冲性分泌率仅在透析患者中显著降低（15 ± 34 vs.46 ± 18; P < 0.05）。(3)脉冲式i-LH和/或生物LH产生率的降低可归因于保守治疗患者每次爆发分泌的LH质量减半。（生物LH：4.9 ±1.9 IU/L）和透析治疗（bio-LH：3.2 ± 0.7，i-LH：2.4 ± 0.6 IU/L）与对照组（bio-LH：6.9 ± 1.3，i-LH：5.4 ± 2.1 IU/L）相比，而LH脉冲频率在对照组和治疗组之间无差异。(4)透析组基础LH释放占总LH分泌率的相对贡献率（25 ± 11%）高于对照组（6.8 ± 3.9%，P <0.005）。(5)尿毒症儿童的i-LH平均血浆浓度显著升高，但bio-LH无此现象。尿毒症儿童的平均bio-LH/i-LH比值的降低是由于基础i-LH分泌的相对增加，导致保守治疗患者的总LH分泌率的bio-LH/i-LH比值显著降低（1.14 ± 0.2 vs. 2.2 ± 0.2）和透析（1.5 ± 0.24），而血浆半衰期的bio-LH/i-LH比值与对照组相似（透析）或甚至增加（保守治疗）。在移植患者中，分泌和清除特征与对照组无显著差异。总之，尿毒症青春期儿童LH分泌模式的特点是血浆半衰期明显延长，LH分泌率降低，与GnRH信号强度和/或垂体反应性不足相一致。可能是由于尚未确定的免疫反应性但生物学无活性的LH片段的蓄积，透析患者中i-LH而非bio-LH的表观基础分泌相对增加，导致i-LH不成比例地增加......
Immunoreactive and bioactive luteinizing hormone in pubertal patients with chronic renal failure. Disturbed pulsatile LH secretion has been suggested to play a role in the etiology of delayed puberty and disturbed reproductive function in chronic renal failure (CRF), but interpretation of gonadotropin secretion from plasma concentration measurements is confounded by alterations in hormone metabolic clearance. To simultaneously investigate LH secretion and clearance in children, we performed multiple-parameter deconvolution analysis of 11-hour overnight serum LH concentration-time series of bioactive (bio-LH) and immunoreactive (i-LH) hormone in 36 pubertal patients (18 boys) with various degrees of CRF and 10 healthy controls matched for sex and pubertal stage. Twelve patients received conservative treatment for advanced but compensated CRF, 12 were treated by dialysis, and 12 were studied after successful renal transplantation. We observed that: (1) the mean (±se) plasma half-lives of bio-LH and i-LH were increased in the dialysis group (155 ± 47 and 201 ± 31 min) and in the patients on conservative treatment (148 ± 45 and 135 ± 70 min) compared to controls (59 ± 28 and 63 ± 21 min; all P < 0.05). The plasma half-life of bio-LH in patients on conservative treatment or after renal transplantation was inversely correlated with glomerular filtration rate (GFR) (r = -0.70; P < 0.0001). (2) Pulsatile bio-LH production rate was independently affected by pubertal stage (P = 0.018) and treatment status (P = 0.017), increasing across pubertal stages and being significantly lower in dialysis patients (20 ± 4 IU/liter * 11 hr) and patients on conservative treatment (28 ± 9) than in controls (43 ± 9; all P < 0.05). In patients on conservative treatment or after transplantation, a significant positive correlation between pulsatile bio-LH production rate was observed (r = 0.53; P < 0.008). Pulsatile i-LH secretion rate was significantly reduced only in dialysis patients (15 ± 34 vs. 46 ± 18; P < 0.05). (3) The reduction of pulsatile i-LH and/or bio-LH production rates was attributable to a halving of the LH mass secreted per burst in patients on conservative (bio-LH: 4.9 ±1.9 IU/liter) and dialysis treatment (bio-LH: 3.2 ± 0.7, i-LH: 2.4 ± 0.6 IU/liter) versus controls (bio-LH: 6.9 ± 1.3, i-LH: 5.4 ± 2.1 IU/liter), whereas the LH pulse frequency was not different between controls and treatment groups. (4) The relative contribution of apparent basal LH release to total secretion rates was higher (25 ± 11%) in patients on dialysis than in controls (6.8 ± 3.9%; P < 0.0.05). (5) Mean plasma concentrations of i-LH, but not bio-LH, were significantly elevated in the uremic children. The reduction of mean bio-LH/i-LH ratio in the uremic children was due to the relative increase in basal i-LH secretion, resulting in a significant reduction of the bio-LH/i-LH ratio of total LH secretion rates in patients on conservative treatment (1.14 ± 0.2 vs. 2.2 ± 0.2) and dialysis (1.5 ± 0.24), whereas the bio-LH/i-LH ratio of plasma half-lives was similar (dialysis) to controls or even increased (conservative treatment). In the transplant patients, none of the secretory and clearance characteristics was significantly different from controls. In conclusion, the secretory pattern of LH in uremic pubertal children is characterized by a distinct increase in plasma half-life, and a reduction of the LH secretion rate compatible with deficient GnRH signal strength and/or pituitary responsiveness. Possibly due to accumulation of as yet undefined immunoreactive but biologically inactive LH fragments, apparent basal secretion of i-LH but not bio-LH is relatively increased in dialyzed patients, resulting in a disproportionate increase of i-LH …