Veldhuis J D, Carlson M L, Johnson M L
Department of Internal Medicine, University of Virginia School of Medicine, Charlottesville 22908.
Proc Natl Acad Sci U S A. 1987 Nov;84(21):7686-90. doi: 10.1073/pnas.84.21.7686.
To investigate patterns of endogenous hormone release, we have proposed a biophysical model in which measured hormone concentrations at any given instant reflect the operation of a suitable cumulation function (secretory input) convolved with an appropriate elimination mechanism (metabolic clearance). The cumulation function underlying a macroscopic hormone secretory burst can be represented by a random (Gaussian) distribution of instantaneous molecular secretory rates, which are centered with some finite and determinable standard deviation about a particular moment in time. The hormone elimination mechanism is described by a mono- or biexponential clearance function. The resultant convolution integral is solved by iterative nonlinear least-squares parameter estimation, in which all plasma hormone concentrations and their variances are considered simultaneously. Experiments with human endocrine time series revealed that the spontaneous secretory patterns of any of multiple distinct anterior pituitary hormones (luteinizing hormone, follicle-stimulating hormone, growth hormone, prolactin, thyrotropin, and adrenocorticotropic hormone) can be described effectively by this parsimonious model. In addition, endogenous hormone disappearance rates determined by deconvolution agreed well with those reported earlier that were determined after exogenous hormone injections. Moreover, this model predicted that durations of underlying secretory impulses are extremely brief; i.e., the standard deviations of the Gaussian distributions of instantaneous secretory rates range from 4.5 min (luteinizing hormone) to 16 min (growth hormone) compared to plasma hormone concentration peaks of 90-140 min in duration. Accordingly, we conclude that observed physiological patterns of fluctuating plasma hormone concentrations can be accounted for by distinct, highly delimited, random bursts of hormone release separated by intervals of secretory quiescence.
为了研究内源性激素释放模式，我们提出了一个生物物理模型，其中在任何给定时刻测得的激素浓度反映了一个合适的累积函数（分泌输入）与一种适当的消除机制（代谢清除）进行卷积的结果。宏观激素分泌脉冲的累积函数可以由瞬时分子分泌率的随机（高斯）分布表示，这些分泌率围绕特定时刻以一定的有限且可确定的标准差为中心。激素消除机制由单指数或双指数清除函数描述。通过迭代非线性最小二乘参数估计求解所得的卷积积分，其中同时考虑所有血浆激素浓度及其方差。对人类内分泌时间序列的实验表明，该简约模型可以有效地描述多种不同的垂体前叶激素（促黄体生成素、促卵泡激素、生长激素、催乳素、促甲状腺激素和促肾上腺皮质激素）中任何一种的自发分泌模式。此外，通过反卷积确定的内源性激素消失率与早期报道的在外源激素注射后确定的消失率非常吻合。而且，该模型预测潜在分泌脉冲的持续时间极短；即，瞬时分泌率的高斯分布的标准差范围从4.5分钟（促黄体生成素）到16分钟（生长激素），而血浆激素浓度峰值的持续时间为90 - 140分钟。因此，我们得出结论，观察到的血浆激素浓度波动的生理模式可以由分泌静止期隔开的不同的、高度限定的、随机的激素释放脉冲来解释。
