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人黄体生成素分泌与清除的体内动力学:通过反卷积力学进行评估

In vivo dynamics of luteinizing hormone secretion and clearance in man: assessment by deconvolution mechanics.

作者信息

Veldhuis J D, Johnson M L

机构信息

Department of Internal Medicine, University of Virginia School of Medicine, Charlottesville 22908.

出版信息

J Clin Endocrinol Metab. 1988 Jun;66(6):1291-300. doi: 10.1210/jcem-66-6-1291.

DOI:10.1210/jcem-66-6-1291
PMID:3372689
Abstract

The dynamics of LH secretion and clearance were studied in vivo in eight healthy young men using a novel multiple parameter deconvolution procedure to resolve underlying secretion and clearance rates simultaneously from serial serum immunoactive LH concentrations. This deconvolution analysis disclosed random LH secretory bursts occurring at a mean (+/- SEM) interpulse interval of 72 +/- 5 min. The frequency of these secretory bursts was 6.9 +/- 0.6 episodes/8 h. Each resolved LH secretory event had an average half-duration of only 7.8 +/- 0.5 min, which was remarkably shorter than the LH concentration peak duration of 60 +/- 6 min. The maximal LH secretory rate achieved within a secretory burst averaged 0.40 +/- 0.05 mIU/min.mL (0.14 IU/min.L), which corresponded to a mass of LH released of 3.2 +/- 0.3 mIU/mL distribution vol (IU/L). By linear regression analysis, both the maximal rate and mass of LH released per secretory burst were positively correlated with the duration of the subsequent interpulse interval (P less than 0.001). In physiological experiments, the mass of LH released per secretory burst was increased by iv GnRH injections or primary gonadal failure, and decreased by sc administration of a selective GnRH antagonist (Nal,Glu-GnRH). The mean endogenous LH production rate calculated by deconvolution [180 +/- 40 mIU/min (0.18 IU/min)] was not different from a nominal value of 228 +/- 80 mIU/min (0.228 IU/min) extrapolated from earlier steady state LH infusions. Deconvolution estimated single phase half-times of endogenous LH disappearance of 87 +/- 8 min, were in general harmony with values of 44-106 min obtained previously in four LH-deficient men injected with purified LH. Moreover, creation of synthetic LH series using our deconvolution estimates yielded 24-h LH pulse profiles similar quantitatively and qualitatively to those in normal men. In summary, we applied a new multiple parameter deconvolution procedure to immunoactive LH pulse profiles to discern the nature of physiological LH secretory events and estimate endogenous LH disappearance rates. These studies in normal men have revealed that 1) LH secretory bursts occur every 72 min; their mean half-duration is 7.8 min; and 3.2 mIU/mL (3.2 IU/L) are released per secretory peak; 2) amplitudes of in vivo LH secretory bursts are augmented in primary gonadal failure and/or by exogenous GnRH injections and attenuated by a GnRH antagonist; 3) the duration of a postsecretory pause is proportional to the amplitude of the preceding LH secretory burst; and (4) 95% of total daily LH release occurs in only 5 h/day.(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

利用一种新型多参数反卷积程序,在8名健康年轻男性体内研究了促黄体生成素(LH)分泌和清除的动力学,以便从连续的血清免疫活性LH浓度中同时解析潜在的分泌率和清除率。这种反卷积分析揭示了随机的LH分泌脉冲,其平均(±标准误)脉冲间期为72±5分钟。这些分泌脉冲的频率为6.9±0.6次/8小时。每个解析出的LH分泌事件的平均半持续时间仅为7.8±0.5分钟,这明显短于LH浓度峰值持续时间60±6分钟。在一次分泌脉冲内达到的最大LH分泌率平均为0.40±0.05毫国际单位/分钟·毫升(0.14国际单位/分钟·升),这相当于释放的LH量为3.2±0.3毫国际单位/毫升分布容积(国际单位/升)。通过线性回归分析,每次分泌脉冲释放的LH最大速率和量均与随后的脉冲间期持续时间呈正相关(P<0.001)。在生理学实验中,静脉注射促性腺激素释放激素(GnRH)或原发性性腺功能衰竭会增加每次分泌脉冲释放的LH量,而皮下注射选择性GnRH拮抗剂(Nal,Glu-GnRH)则会减少。通过反卷积计算的平均内源性LH产生率[180±40毫国际单位/分钟(0.18国际单位/分钟)]与从早期LH稳态输注推断出的标称值228±80毫国际单位/分钟(0.228国际单位/分钟)没有差异。反卷积估计内源性LH消失的单相半衰期为87±8分钟,这与之前在4名注射纯化LH的LH缺乏男性中获得的44 - 106分钟的值总体一致。此外,使用我们的反卷积估计创建的合成LH序列产生的24小时LH脉冲图谱在数量和质量上与正常男性的相似。总之,我们将一种新的多参数反卷积程序应用于免疫活性LH脉冲图谱,以辨别生理性LH分泌事件的性质并估计内源性LH消失率。这些在正常男性中的研究表明:1)LH分泌脉冲每72分钟发生一次;其平均半持续时间为7.8分钟;每个分泌峰值释放3.2毫国际单位/毫升(3.2国际单位/升);2)原发性性腺功能衰竭和/或外源性GnRH注射会增加体内LH分泌脉冲的幅度,而GnRH拮抗剂会使其减弱;3)分泌后暂停的持续时间与前一次LH分泌脉冲的幅度成正比;4)每日LH总释放量的95%仅在每天5小时内发生。(摘要截断于400字)

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