Validation of deconvolution analysis of LH secretion and half-life

1994 ◽  
Vol 267 (1) ◽  
pp. R202-R211
Author(s):  
T. Mulligan ◽  
H. A. Delemarre-van de Waal ◽  
M. L. Johnson ◽  
J. D. Veldhuis
Keyword(s):  
Half Life ◽  
Hormone Secretion ◽  
Simulated Data ◽  
Pulse Signal ◽  
Deconvolution Analysis ◽  
Pulse Detection ◽  
Experimental Variation ◽  
Deconvolution Techniques ◽  
Lh Secretion

Deconvolution methods constitute a class of analytic tools to quantitate hormone secretion and/or clearance in vivo. Although mathematically rigorous, deconvolution techniques have assumed, rather than proven, validity. Accordingly, we tested the validity of deconvolution analysis on true-positive human, animal (sheep and monkey), and computer-simulated data using the luteinizing hormone (LH) pulse signal as a relevant paradigm. We found that multiparameter deconvolution analysis has high discriminative sensitivity (human data 91%, animal 81%, computer-stimulated 95%) and specificity (human 90%, animal 81%, computer-simulated 100%). Sensitivity was impaired by low secretory burst amplitude (< 0.1 IU.l-1.min-1), short interpulse interval (< 60 min), infrequent venous sampling (every 20-30 min), and high random experimental variation (e.g., noise > 15%). Specificity was hindered by noise. Deconvolution accurately characterized the unknown hormone half-life (r = +0.994) and production rate (r = +0.990). Interoperator reliability was high when statistically based criteria for secretory pulse detection were applied. We conclude that multiparameter deconvolution, within recognizable constraints, is a valid and reliable tool for in vivo investigation of hormone secretion and half-life.

Variability of pulsatile luteinizing hormone secretion in young male volunteers

1994 ◽  
Vol 131 (3) ◽  
pp. 263-272 ◽  
Author(s):  
Carl-Joachim Partsch ◽  
Sievert Abrahams ◽  
Niels Herholz ◽  
Michael Peter ◽  
Johannes D Veldhuis ◽  
...  
Keyword(s):  
Luteinizing Hormone ◽  
Half Life ◽  
Hormone Secretion ◽  
Young Male ◽  
Interpulse Interval ◽  
Luteinizing Hormone Secretion ◽  
Individual Subject ◽  
Deconvolution Analysis ◽  
Pulse Detection ◽  
Male Volunteers

Partsch C-J, Abrahams S, Herholz N, Peter M, Veldhuis JD, Sippell WG. Variability of pulsatile luteinizing hormone secretion in young male volunteers. Eur J Endocrinol 1994;131:263–72. ISSN 0804–4643 Characteristics of spontaneous pulsatile luteinizing hormone secretion were compared in ten young healthy men in three 24-h profiles obtained at intervals of 14 days and 3 months. The ages of the volunteers ranged from 19 to 25 years, and heights and weights were within normal limits. Blood samples were taken at 10-min intervals and plasma luteinizing hormone (LH) was determined in the same immunoradiometric assay using monoclonal antibodies. Conventional pulse detection was carried out with PULSAR and CLUSTER programs. In addition, a simultaneous multiple parameter DECONVOLUTION was applied. As a group, no significant differences between the three profile series were found for any of the calculated parameters of LH concentration or LH secretion. However, most parameters showed low correlation coefficients between the three study periods, suggesting that substantial individual variations might contribute to the more reliable group results. Median coefficients of variation (cv) for the individual subject ranged from 9.7% (interpulse interval and endogenous half-life) to 37.7% (mass per burst). However, the maximal individual cv observed was 78.4%. Intra-individual variability was lower than the variability between subjects for quantitative properties of LH concentration and secretion, although not significantly so for all parameters. In conventional pulse detection, the highest individual reliability was found for mean and integrated LH concentrations (median cv 10.2 and 13.7%, respectively), number of pulses per 24 h (CLUSTER, median cv 12.2%), mean pulse amplitude (PULSAR, median cv 10%) and interpulse interval (CLUSTER, median cv 9.7%). In DECONVOLUTION analysis, the endogenous LH half-life (median cv 9.7%), secretory burst amplitude (median cv 14.8%) and interburst interval (median cv 14.5%) revealed the lowest intra-individual variation. In contrast, the half-duration of a secretory episode and the mass of LH secreted per burst proved to be the least reliable measures (median cv 32.7% and 37.7%, respectively). Calculated endogenous LH production rates correlated highly (p < 0.01) across all three sessions. The relative frequencies of the LH peak amplitudes/heights and peak widths (durations) showed almost identical distribution curves for all three sampling periods. In conclusion, a high reproducibility of group results for both integrative parameters and pulse characteristics of LH concentrations and secretion were found in normal men. However, intra-individual reliability was variable and at times considerable, depending on the parameter chosen. These observations suggest caution in the interpretation of single LH profiles from individual subjects or patients unless the variation reported herein is considered. C-J Partsch, Institut für Reproduktionsmedizin, Westfälische Wilhelms-Universität, Steinfurter Straβe 107, D-48149 Münster, Germany

scholarly journals Sensitivity and specificity of pulse detection using a new deconvolution method

2009 ◽  
Vol 297 (2) ◽  
pp. E538-E544 ◽  
Author(s):  
Peter Y. Liu ◽  
Daniel M. Keenan ◽  
Petra Kok ◽  
Vasantha Padmanabhan ◽  
Kevin T. O'Byrne ◽  
...  
Keyword(s):  
Sensitivity And Specificity ◽  
Computer Simulations ◽  
False Negative ◽  
Simulated Data ◽  
Information Criterion ◽  
Detection Sensitivity ◽  
Detection Accuracy ◽  
Sprague Dawley ◽  
Deconvolution Analysis ◽  
Pulse Detection

Quantifying pulsatile secretion from serial hormone concentration measurements (deconvolution analysis) requires automated, objective, and accurate detection of pulse times to ensure valid estimation of secretion and elimination parameters. Lack of validated pulse identification constitutes a major deficiency in the deconvolution field, because individual pulse size and number reflect regulated processes that are critical for the function and response of secretory glands. To evaluate deconvolution pulse detection accuracy, four empirical models of true-positive markers of pituitary (LH) pulses were used. 1) Sprague-Dawley rats had recordings of hypothalamic arcuate nucleus multiunit electrical activity, 2) ovariectomized ewes underwent sampling of hypothalamo-pituitary gonadotropin-releasing hormone (GnRH pulses), 3) healthy young men were infused with trains of biosynthetic LH pulses after GnRH receptor blockade, and 4) computer simulations of pulsatile LH profiles were constructed. Outcomes comprised sensitivity, specificity, and receiver-operating characteristic curves. Sensitivity and specificity were 0.93 and 0.97, respectively, for combined empirical data in the rat, sheep, and human ( n = 156 pulses) and 0.94 and 0.92, respectively, for computer simulations ( n = 1,632 pulses). For simulated data, pulse-set selection by the Akaike information criterion yielded slightly higher sensitivity than by the Bayesian information criterion, and the reverse was true for specificity. False-positive errors occurred primarily at low-pulse amplitude, and false-negative errors occurred principally with close pulse proximity. Random variability (noise), sparse sampling, and rapid pulse frequency reduced pulse detection sensitivity more than specificity. We conclude that an objective automated pulse detection deconvolution procedure has high sensitivity and specificity, thus offering a platform for quantitative neuroendocrine analyses.

Reanalysis of the rat proestrous LH surge by deconvolution analysis

1993 ◽  
Vol 265 (1) ◽  
pp. R240-R245
Author(s):  
J. D. Veldhuis ◽  
M. L. Johnson ◽  
R. V. Gallo
Keyword(s):  
Luteinizing Hormone ◽  
Half Life ◽  
Fold Increase ◽  
Basal Secretion ◽  
Release Rates ◽  
Deconvolution Analysis ◽  
Lh Surge ◽  
Time Profiles ◽  
Burst Amplitude ◽  
Lh Secretion

To evaluate the temporal mechanisms that give rise to the spontaneous proestrous surge of luteinizing hormone (LH) in the rat, we have applied deconvolution analysis to earlier immunoreactive LH concentration vs. time profiles obtained by sampling blood in proestrus at 2- to 3-min intervals in 10 animals over a span of 160-300 min. Six other animals were bled in 6-min intervals on day 1 of diestrus. Deconvolution analysis permitted us to calculate the number, duration, amplitude (maximal release rates), and mass of underlying LH secretory bursts and to simultaneously estimate basal secretion and the half-life of endogenous LH in each animal. Proestrus rats exhibited a significant increase in the number of computer-identified LH secretory bursts per hour (1.8 +/- 0.2 vs. 1.1 +/- 0.01 on diestrus, P < 0.01), with a corresponding reduction in the LH intersecretory burst interval from 61 +/- 6.4 min (diestrus) to 25 +/- 2.7 min (proestrus, P < 0.01). There was a remarkable 16-fold increase in the mass of LH secreted per burst, which rose from 72 +/- 5.2 to 1,230 +/- 200 ng/ml (P < 0.01). This resulted from a sixfold increase in LH secretory burst amplitude and a doubling of burst duration. The total amount of LH released in a burstlike fashion during the proestrous LH surge rose 20-fold, and calculated basal LH secretion increased to approximately 25% of this value. Of interest, the computed half-life of endogenous LH also increased from 10 +/- 1.1 to 19 +/- 3.7 min (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Deconvolution analysis of bioassayable LH secretion and half‐life in men with idiopathic oligoasthenospermia

1997 ◽  
Vol 20 (2) ◽  
pp. 118-125 ◽  
Author(s):  
A. REYES‐FUENTES ◽  
M. E. CHAVARRÍA ◽  
G. AGUILERA ◽  
A. ROSADO ◽  
A. IRANMANESH ◽  
...  
Keyword(s):  
Half Life ◽  
Deconvolution Analysis ◽  
Lh Secretion

THE APPLICATION OF DECONVOLUTION ANALYSIS TO ELUCIDATE THE PULSATILE NATURE OF GROWTH HORMONE SECRETION USING A VARIABLE HALF-LIFE OF GROWTH HORMONE

1990 ◽  
Vol 32 (6) ◽  
pp. 739-747 ◽  
Author(s):  
P. C. HINDMARSH ◽  
D. R. MATTHEWS ◽  
C. BRAIN ◽  
P. J. PRINGLE ◽  
C. G. D. BROOK
Keyword(s):  
Growth Hormone ◽  
Half Life ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Deconvolution Analysis

scholarly journals Selective optogenetic activation of arcuate kisspeptin neurons generates pulsatile luteinizing hormone secretion

2015 ◽  
Vol 112 (42) ◽  
pp. 13109-13114 ◽  
Author(s):  
Su Young Han ◽  
Timothy McLennan ◽  
Katja Czieselsky ◽  
Allan E. Herbison
Keyword(s):  
Luteinizing Hormone ◽  
Hormone Secretion ◽  
Neural Mechanism ◽  
Luteinizing Hormone Secretion ◽  
Gonadotropin Secretion ◽  
Steroid Dependence ◽  
Ovariectomized Mice ◽  
Lh Secretion

Normal reproductive functioning in mammals depends upon gonadotropin-releasing hormone (GnRH) neurons generating a pulsatile pattern of gonadotropin secretion. The neural mechanism underlying the episodic release of GnRH is not known, although recent studies have suggested that the kisspeptin neurons located in the arcuate nucleus (ARN) may be involved. In the present experiments we expressed channelrhodopsin (ChR2) in the ARN kisspeptin population to test directly whether synchronous activation of these neurons would generate pulsatile luteinizing hormone (LH) secretion in vivo. Characterization studies showed that this strategy targeted ChR2 to 70% of all ARN kisspeptin neurons and that, in vitro, these neurons were activated by 473-nm blue light with high fidelity up to 30 Hz. In vivo, the optogenetic activation of ARN kisspeptin neurons at 10 and 20 Hz evoked high amplitude, pulse-like increments in LH secretion in anesthetized male mice. Stimulation at 10 Hz for 2 min was sufficient to generate repetitive LH pulses. In diestrous female mice, only 20-Hz activation generated significant increments in LH secretion. In ovariectomized mice, 5-, 10-, and 20-Hz activation of ARN kisspeptin neurons were all found to evoke LH pulses. Part of the sex difference, but not the gonadal steroid dependence, resulted from differential pituitary sensitivity to GnRH. Experiments in kisspeptin receptor-null mice, showed that kisspeptin was the critical neuropeptide underlying the ability of ARN kisspeptin neurons to generate LH pulses. Together these data demonstrate that synchronized activation of the ARN kisspeptin neuronal population generates pulses of LH.

Kinetics of Various 99mTc-Sn-Pyrophosphate Compounds in the Rat

1977 ◽  
Vol 16 (04) ◽  
pp. 157-162 ◽  
Author(s):  
C. Schümichen ◽  
B. Mackenbrock ◽  
G. Hoffmann
Keyword(s):  
Normal Saline ◽  
Half Life ◽  
Compound A ◽  
Short Half Life ◽  
Low Concentrations ◽  
The Stability ◽  
Kinetics Of ◽  
In Vitro Stability

SummaryThe bone-seeking 99mTc-Sn-pyrophosphate compound (compound A) was diluted both in vitro and in vivo and proved to be unstable both in vitro and in vivo. However, stability was much better in vivo than in vitro and thus the in vitro stability of compound A after dilution in various mediums could be followed up by a consecutive evaluation of the in vivo distribution in the rat. After dilution in neutral normal saline compound A is metastable and after a short half-life it is transformed into the other 99mTc-Sn-pyrophosphate compound A is metastable and after a short half-life in bone but in the kidneys. After dilution in normal saline of low pH and in buffering solutions the stability of compound A is increased. In human plasma compound A is relatively stable but not in plasma water. When compound B is formed in a buffering solution, uptake in the kidneys and excretion in urine is lowered and blood concentration increased.It is assumed that the association of protons to compound A will increase its stability at low concentrations while that to compound B will lead to a strong protein bond in plasma. It is concluded that compound A will not be stable in vivo because of a lack of stability in the extravascular space, and that the protein bond in plasma will be a measure of its in vivo stability.

Half-Life of Platelet Factor 4 (PF-4) in Plasma and Platelets from Macaca Mulatta

1977 ◽  
Vol 37 (01) ◽  
pp. 073-080 ◽  
Author(s):  
Knut Gjesdal ◽  
Duncan S. Pepper
Keyword(s):  
Macaca Mulatta ◽  
Half Life ◽  
Human Platelet ◽  
Gel Filtration ◽  
Platelet Factor 4 ◽  
Active Protein ◽  
Platelet Factor ◽  
Membrane Bound

SummaryHuman platelet factor 4 (PF-4) showed a reaction of complete identity with PF-4 from Macaca mulatta when tested against rabbit anti-human-PF-4. Such immunoglobulin was used for quantitative precipitation of in vivo labelled PF-4 in monkey serum. The results suggest that the active protein had an intra-platelet half-life of about 21 hours. In vitro 125I-labelled human PF-4 was injected intravenously into two monkeys and isolated by immuno-precipita-tion from platelet-poor plasma and from platelets disrupted after gel-filtration. Plasma PF-4 was found to have a half-life of 7 to 11 hours. Some of the labelled PF-4 was associated with platelets and this fraction had a rapid initial disappearance rate and a subsequent half-life close to that of plasma PF-4. The results are compatible with the hypothesis that granular PF-4 belongs to a separate compartment, whereas membrane-bound PF-4 and plasma PF-4 may interchange.

Turnover of Human Extrinsic (Tissue-Type) Plasminogen Activator in Rabbits

1981 ◽  
Vol 46 (03) ◽  
pp. 658-661 ◽  
Author(s):  
C Korninger ◽  
J M Stassen ◽  
D Collen
Keyword(s):  
Plasminogen Activator ◽  
Intravenous Injection ◽  
Active Site ◽  
Half Life ◽  
Degradation Products ◽  
Gel Filtration ◽  
Tissue Type ◽  
Organ Distribution ◽  
Small Rise

SummaryThe turnover of highly purified human extrinsic plasminogen activator (EPA) (one- and two-chain form) was studied in rabbits. Following intravenous injection, EPA-activity declined rapidly. The disappearance rate of EPA from the plasma could adequately be described by a single exponential term with a t ½ of approximately 2 min for both the one-chain and two-chain forms of EPA.The clearance and organ distribution of EPA was studied by using 125I-labeled preparations. Following intravenous injection of 125I-1abeled EPA the radioactivity disappeared rapidly from the plasma also with a t ½ of approximately 2 min down to a level of 15 to 20 percent, followed by a small rise of blood radioactivity. Gel filtration of serial samples revealed that the secondary increase of the radioactivity was due to the reappearance of radioactive breakdown products in the blood. Measurement of the organ distribution of 125I at different time intervals revealed that EPA was rapidly accumulated in the liver, followed by a release of degradation products in the blood.Experimental hepatectomy markedly prolonged the half-life of EPA in the blood. Blocking the active site histidine of EPA had no effect on the half-life of EPA in blood nor on the gel filtration patterns of 125I in serial plasma samples.It is concluded that human EPA is rapidly removed from the blood of rabbits by clearance and degradation in the liver. Recognition by the liver does not require a functional active site in the enzyme. Neutralization in plasma by protease inhibitors does not represent a significant pathway of EPA inactivation in vivo.

Clearance and In Vivo Release by Heparin of Human Platelet Factor 4 (PF4) in the Rabbit

1984 ◽  
Vol 52 (02) ◽  
pp. 157-159 ◽  
Author(s):  
M Prosdocimi ◽  
N Scattolo ◽  
A Zatta ◽  
F Fabris ◽  
F Stevanato ◽  
...  
Keyword(s):  
Half Life ◽  
Human Platelet ◽  
Slow Component ◽  
Platelet Factor 4 ◽  
Platelet Factor ◽  
In Vivo Release ◽  
Partial Release ◽  
Different Doses ◽  
New Zealand Rabbits

Summary13 male New Zealand rabbits were injected with two different doses (25 μg/Kg and 100 μg/Kg) of human platelet factor 4 antigen (PF4). The disappearance of the protein was extremely fast with an half-life for the fast component of 1.07 ± 0.16 and 1.76 ± 0.11 min respectively. The half-life for the slow component, detectable only with the highest dosage, was 18.8 min.The administration of 2500 I.U. of heparin 30 min after PF4 administration induced a partial release of the injected protein and its clearance from plasma was slow, with half-life of 23.3 ± 5.9 min and 30.9 ± 2.19 min respectively.

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