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)

Evaluation of LH secretory dynamics during the rat proestrous LH surge

1999 ◽  
Vol 276 (1) ◽  
pp. R219-R225 ◽  
Author(s):  
Kathleen M. Hoeger ◽  
Lisa A. Kolp ◽  
Frank J. Strobl ◽  
Johannes D. Veldhuis
Keyword(s):  
Half Life ◽  
Approximate Entropy ◽  
Fold Increase ◽  
Pituitary Hormones ◽  
Release Process ◽  
Secretory Rate ◽  
Lh Surge ◽  
Concentration Time Series ◽  
Lh Release ◽  
Lh Secretion

The preovulatory luteinizing hormone (LH) surge results from the integration of complex interactions among gonadal steroids and hypothalamic and pituitary hormones. To evaluate changes in LH secretory dynamics that occur during the rat LH surge, we have 1) obtained frequently sampled serum LH concentration time series, 2) used both waveform-dependent and waveform-independent convolution analyses, and 3) independently assessed proestrous LH half-life and basal non-gonadotropin-releasing hormone (GnRH)-dependent LH secretion during the LH surge. Waveform-independent pulse analysis revealed a 24-fold increase in the maximal pulsatile LH secretory rate attained during late proestrus compared with early proestrus. A 15-fold increase was quantified for the mean LH secretory rate. In complementary analyses, we applied a measured LH half-life of 17 ± 2.7 min and a median basal LH secretion rate of 0.0046 μg ⋅ l−1 ⋅ min−1 for convolution analysis, revealing a 16-fold increase in the mass of LH released/burst and more than sixfold rise in the amplitude of the secretory peaks. Evaluation of the approximate entropy of the LH surge profiles was performed, showing an increase in the orderliness of the LH release process during the surge. We conclude that both quantitative (mass/burst) and qualitative (approximate entropy) features of LH release are regulated during the proestrous LH surge.

scholarly journals Changes in the kinetics and biopotency of luteinizing hormone in hemodialyzed men during treatment with recombinant human erythropoietin.

1994 ◽  
Vol 5 (5) ◽  
pp. 1208-1215
Author(s):  
F Schaefer ◽  
B van Kaick ◽  
J D Veldhuis ◽  
G Stein ◽  
K Schärer ◽  
...  
Keyword(s):  
Luteinizing Hormone ◽  
Half Life ◽  
Recombinant Human Erythropoietin ◽  
Cell Mass ◽  
Elimination Kinetics ◽  
Deconvolution Analysis ◽  
Human Erythropoietin ◽  
Change In Mean ◽  
Plasma Half Life

To investigate the effect of recombinant human erythropoietin (rh-EPO) on the hypothalamo-pituitary-gonadal axis in end-stage renal failure, plasma luteinizing hormone (LH) concentration release was assessed by frequent blood sampling (every 10 min), both during an 8-h baseline period and after stimulation with an iv bolus of gonadotropin-releasing hormone (GnRH). Seven adult hemodialyzed men were studied before and after partial correction of anemia by rh-EPO treatment. LH was determined by an in vitro Leydig cell bioassay (bio-LH) and a highly sensitive immunoradiometric assay. Pulsatile bio-LH secretion and clearance characteristics were assessed by multiple-parameter deconvolution analysis. Although the rh-EPO treatment did not lead to a change in average concentrations of plasma bio-LH, the mass of hormone released per secretory burst more than doubled, and the estimated bio-LH production rate increased from 8.8 +/- 2.3 to 15.6 +/- 5.2 IU/L per hour (P = 0.05). The lack of change in mean plasma bio-LH is explained by a simultaneous decrease in plasma half-life from 106 +/- 27 to 67 +/- 19 min (P < 0.02). The decrease in the plasma half-life of bio-LH was closely associated with the rise in hematocrit, suggesting an effect of the increased red blood cell mass on LH distribution space and elimination kinetics. As a consequence of the changes in hormone kinetics, the incremental amplitudes of the plasma concentration pulses of bio-LH increased from 112 to 121% of nadir levels (P < 0.05), resulting in a more distinctly pulsatile pattern of hormone signals.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Effect of androgen on Kiss1 expression and luteinizing hormone release in female rats

2017 ◽  
Vol 233 (3) ◽  
pp. 281-292 ◽  
Author(s):  
Kinuyo Iwata ◽  
Yuyu Kunimura ◽  
Keisuke Matsumoto ◽  
Hitoshi Ozawa
Keyword(s):  
Luteinizing Hormone ◽  
Arcuate Nucleus ◽  
Female Rats ◽  
Hormone Release ◽  
Lh Surge ◽  
Continuous Release ◽  
Ovulatory Dysfunction ◽  
Lh Release ◽  
Gonadotrophin Releasing Hormone ◽  
Lh Secretion

Hyperandrogenic women have various grades of ovulatory dysfunction, which lead to infertility. The purpose of this study was to determine whether chronic exposure to androgen affects the expression of kisspeptin (ovulation and follicle development regulator) or release of luteinizing hormone (LH) in female rats. Weaned females were subcutaneously implanted with 90-day continuous-release pellets of 5α-dihydrotestosterone (DHT) and studied after 10 weeks of age. Number of Kiss1-expressing cells in both the anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC) was significantly decreased in ovary-intact DHT rats. Further, an estradiol-induced LH surge was not detected in DHT rats, even though significant differences were not observed between DHT and non-DHT rats with regard to number of AVPV Kiss1-expressing cells or gonadotrophin-releasing hormone (GnRH)-immunoreactive (ir) cells in the presence of high estradiol. Kiss1-expressing and neurokinin B-ir cells were significantly decreased in the ARC of ovariectomized (OVX) DHT rats compared with OVX non-DHT rats; pulsatile LH secretion was also suppressed in these animals. Central injection of kisspeptin-10 or intravenous injection of a GnRH agonist did not affect the LH release in DHT rats. Notably, ARC Kiss1-expressing cells expressed androgen receptors (ARs) in female rats, whereas only a few Kiss1-expressing cells expressed ARs in the AVPV. Collectively, our results suggest excessive androgen suppresses LH surge and pulsatile LH secretion by inhibiting kisspeptin expression in the ARC and disruption at the pituitary level, whereas AVPV kisspeptin neurons appear to be directly unaffected by androgen. Hence, hyperandrogenemia may adversely affect ARC kisspeptin neurons, resulting in anovulation and menstrual irregularities.

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

Impact of pulsatility on the ensemble orderliness (approximate entropy) of neurohormone secretion

2001 ◽  
Vol 281 (6) ◽  
pp. R1975-R1985 ◽  
Author(s):  
J. D. Veldhuis ◽  
M. L. Johnson ◽  
O. L. Veldhuis ◽  
M. Straume ◽  
S. M. Pincus
Keyword(s):  
Half Life ◽  
Young Male ◽  
Approximate Entropy ◽  
Pulse Amplitude ◽  
Interval Length ◽  
Normal Female ◽  
Pulse Trains ◽  
Burst Amplitude ◽  
The Impact ◽  
Lh Secretion

Regular patterns of neurohormone secretion are driven by underlying pulsatile and subordinate (feedback sensitive) dynamics. Measures of time-series orderliness, e.g., the approximate entropy (ApEn) statistic (Pincus SM. Proc Natl Acad Sci 88: 2297–2301, 1991), vividly discriminate pathological and physiological patterns of hormone release. To investigate how specific pulsatility features impact regularity estimates, we have examined the sensitivity of the ApEn metric to systematic variations in the frequency, amplitude, and half-life of simulated neurohormone pulse trains (Veldhuis JD, Carlson ML, and Johnson ML. Proc Natl Acad Sci 84: 7686–7690, 1987) and compared the impact of a high vs. low baseline luteinizing hormone (LH) pattern regularity state mimicking the normal female luteal phase and the young male, respectively. Shortening the interpulse interval length elevated ApEn in both pulsatility models, thereby signifying greater ensemble series irregularity. The frequency sensitivity of ApEn was robust to several complementary renditions of ApEn and to variations in experimental uncertainty, basal (nonpulsatile) LH secretion, and secretory burst amplitude. ApEn rose with increasing hormone half-life, especially in the face of low baseline variability emulated by midluteal LH secretion profiles. High variability of secretory burst amplitude, pulse duration, or interpeak intervals increased ApEn in the more orderly femalelike construct; in the highly irregular malelike LH pulse model, these variability changes had little effect on ApEn. In summary, the ensemble regularity statistic, ApEn, quantifies unequal pattern orderliness in neurohormone pulse trains with minimal dependence on mean pulse amplitude, interpulse baseline, or (subthreshold) sample uncertainty. Thus ApEn monitors changing secretory event frequency and interpulse variability with sensitivity to starting pattern regularity, providing a mechanistic linkage between model evolution and statistical change.

Age-Related Changes in the Regulation of Luteinizing Hormone Secretion by Estrogen in Women

2002 ◽  
Vol 227 (7) ◽  
pp. 455-464 ◽  
Author(s):  
Susanna J. Park ◽  
Laura T. Goldsmith ◽  
Gerson Weiss
Keyword(s):  
Menstrual Cycle ◽  
Luteinizing Hormone ◽  
Hormone Secretion ◽  
Luteinizing Hormone Secretion ◽  
Estrogen Regulation ◽  
Lh Surge ◽  
Age Related ◽  
Hypothalamic Pituitary Axis ◽  
The Many ◽  
Lh Secretion

Despite the many studies that have been conducted using both primate and human models to understand the control of the menstrual cycle, there are many aspects of the hormonal dynamics of the menstrual cycle that are not understood. This Minireview summarizes the changes in estrogen regulation of luteinizing hormone (LH) secretion that occur throughout life in women from the time of maturation of the hypothalamic-pituitary axis resulting in the occurrence of the LH surge during puberty, through the reproductive years, to the changes in the regulation of the LH surge during premenopause and, subsequently, menopause.

EFFECT OF PENTOBARBITAL ANAESTHESIA ON LUTEINIZING HORMONE LEVELS IN INTACT AND OVARIECTOMIZED EWES

1975 ◽  
Vol 80 (1) ◽  
pp. 32-41 ◽  
Author(s):  
Allen R. Ellicott ◽  
Henry J. Benoit ◽  
Rudi Borth ◽  
Ronald C. Strickler ◽  
C. Allan Woolever
Keyword(s):  
Luteinizing Hormone ◽  
Control Period ◽  
Serum Levels ◽  
Regulatory Mechanisms ◽  
Time Pattern ◽  
Lh Surge ◽  
Deep Anaesthesia ◽  
Lh Secretion ◽  
Light Sleep ◽  
Pentobarbital Anaesthesia

ABSTRACT In six intact ewes, deep anaesthesia lasting 1—2 h was induced with pentobarbital given intravenously at the onset of oestrus. In a second group of six ovariectomized ewes, light pentobarbital anaesthesia was induced following a control period of 4 h and then maintained for 2, 3, or 4 h. No drug was given to control animals (seven in the first group, three in the second). Serum levels of luteinizing hormone (LH) were determined by radioimmunoassay hourly in the first group, and at intervals of 5 or 10 min in the second. In the oestrous ewes, pentobarbital did not prevent or modify the expected LH surge. In the ovariectomized ewes, the drug, while not affecting the pulsatile release pattern of LH, reduced average LH levels to about half their control values (P < 0.001) when given in a dosage maintaining 3 or 4 h of light sleep; the 2-h dosage had no such effect. These differential effects of pentobarbital indicate that LH secretion in ewes is regulated by more than one mechanism. In particular, our findings are consistent with a hypothesis that there are, in ovariectomized ewes, independent central regulatory mechanisms for the amount of LH released, and for the time pattern of its release.

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.

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