Schaefer F, Veldhuis J D, Robertson W R, Dunger D, Schärer K
Division of Pediatric Nephrology, University Children's Hospital, Heidelberg, Germany.
Kidney Int. 1994 May;45(5):1465-76. doi: 10.1038/ki.1994.191.
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 over-night 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.(ABSTRACT TRUNCATED AT 400 WORDS)
有研究表明,促黄体生成素(LH)脉冲式分泌紊乱在慢性肾衰竭(CRF)患者青春期发育延迟及生殖功能紊乱的病因中起一定作用。然而,通过血浆浓度测量来解释促性腺激素分泌情况时,会因激素代谢清除率的改变而受到干扰。为同时研究儿童的LH分泌及清除情况,我们对36例不同程度CRF的青春期患者(18名男孩)及10名性别和青春期阶段匹配的健康对照者进行了11小时夜间血清中生物活性LH(bio-LH)和免疫反应性LH(i-LH)激素浓度-时间序列的多参数反卷积分析。12例患者因晚期但代偿性CRF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。我们观察到:(1)与对照组(59±28分钟和63±21分钟;所有P<0.05)相比,透析组(155±47分钟和201±31分钟)及接受保守治疗的患者(148±45分钟和135±70分钟)中bio-LH和i-LH的血浆平均半衰期延长。接受保守治疗或肾移植后的患者中,bio-LH的血浆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bio-LH生成率独立受青春期阶段(P=0.018)和治疗状态(P=0.017)影响,随青春期阶段进展而增加,且透析患者(20±4 IU/升×11小时)和接受保守治疗的患者(28±9)显著低于对照组(43±9;所有P<0.05)。在接受保守治疗或移植后的患者中,观察到脉冲式bio-LH生成率之间存在显著正相关(r=0.53;P<0.008)。仅透析患者的脉冲式i-LH分泌率显著降低(15±34对46±18;P<0.05)。(3)保守治疗(bio-LH:4.9±1.9 IU/升)和透析治疗(bio-LH:3.2±0.7,i-LH:2.4±0.6 IU/升)患者与对照组(bio-LH:6.9±1.3,i-LH:5.4±2.1 IU/升)相比,脉冲式i-LH和/或bio-LH生成率降低是由于每次脉冲分泌的LH量减半,而对照组和治疗组之间的LH脉冲频率无差异。(摘要截选至400字)