scholarly journals Analysis of the impact of intravenous LH pulses versus continuous LH infusion on testosterone secretion during GnRH-receptor blockade

2012 ◽  
Vol 303 (10) ◽  
pp. R994-R1002 ◽  
Author(s):  
Johannes D. Veldhuis ◽  
Peter Y. Liu ◽  
Paul Y. Takahashi ◽  
Suanne M. Weist ◽  
Jean R. Wigham

Gonadotrophin-releasing hormone (GnRH) pulsatility is required for optimal luteinizing hormone (LH) secretion, but whether LH pulsatility is required for physiological testosterone (T) secretion is not known. To test the postulate that pulses of recombinant human (rh) LH stimulate greater T secretion than continuous infusion of the same dose, a potent selective GnRH antagonist was administered overnight to 19 healthy men ages 18–49 yr. Subjects then received saline or rhLH intravenously continuously or as 6-min pulses intravenously every 1 or 2 h at the same total dose. Blood was sampled every 10 min for 10 h to quantify T responses. For the four interventions, the descending rank order of mean LH and mean T concentrations was 1-h = 2-h rhLH pulses > continuous rhLH > saline ( P < 10−3). Plateau LH and T concentrations correlated positively ( R2 = 0.943, P = 0.029) as did LH concentrations and LH half-lives ( R2 = 0.962, P = 0.019). Percentage pulsatile T secretion assessed by deconvolution analysis (Keenan DM, Takahashi PY, Liu PY, Roebuck PD, Nehra AX, Iranmanesh A, Veldhuis JD. Endocrinology 147: 2817–2828, 2006) was the highest ( P = 0.019), and half-time to attain peak T concentrations was the shortest ( P < 10−6), for 1-h rhLH pulses. Approximate entropy (a pattern-regularity measure) revealed more orderly T secretion for 1- than 2-h rhLH pulses ( P = 0.0076). Accordingly, a pulsatile LH signal, while not obligatory to maintain mean T concentrations, controls the mean plasma LH concentration and determines quantifiable patterns of T secretion. These data introduce the question whether blood T patterns in turn supervise distinctive target-tissue responses.

2001 ◽  
Vol 281 (6) ◽  
pp. R1975-R1985 ◽  
Author(s):  
J. D. Veldhuis ◽  
M. L. Johnson ◽  
O. L. Veldhuis ◽  
M. Straume ◽  
S. M. Pincus

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.


2002 ◽  
pp. 310-318 ◽  
Author(s):  
M Maccario ◽  
JD Veldhuis ◽  
F Broglio ◽  
LD Vito ◽  
E Arvat ◽  
...  

OBJECTIVE: To extend the insights on the action of GH secretagogues (GHS) on pituitary function, we studied the impact of intermittent daily s.c. administration of a peptidyl GHS, hexarelin (HEX), on 24-h GH, PRL, ACTH and cortisol release in healthy volunteers. DESIGN: We investigated the impact of two or three times daily s.c. administration of a short-acting peptidyl GHS, the hexapeptide HEX (1.5 microg/kg) on 24-h GH, PRL, ACTH and cortisol secretion (sampling every 20 min) in six normal young men. To monitor possible down-regulation, the effect of 1 microg/kg i.v. HEX at the end of each 24-h sampling period was studied. METHODS: Multi-parameter deconvolution analysis was used to quantitate pulsatile GH, PRL, ACTH and cortisol secretion and estimate the corresponding hormone half-lives. Complementary to deconvolution analysis, approximate entropy was used as a scale- and model-independent statistic to quantify the serial orderliness or pattern regularity of hormone measurements. RESULTS: Mean and integrated (24-h) serum GH concentrations were increased from baseline values to the same extent by two and three HEX injections. Both HEX schedules equally increased GH secretory burst mass (but not burst frequency), mean daily GH production rate, GH half-life and irregularity of GH release patterns. No change occurred in the secretion of IGF-I, PRL, ACTH and cortisol. Intravenous HEX at the end of each spontaneous 24-h profile induced a significant rise in GH, PRL, ACTH and cortisol. Prior HEX administration blunted the GH response, abolished that of ACTH and cortisol and did not modify the PRL increase. CONCLUSIONS: The study showed that two or three daily s.c. injections of HEX augmented 24-h GH secretion equally, amplifying selectively GH secretory pulse mass without altering lactotroph and corticotroph secretion. IGF-I levels were not modified by these 1-day HEX treatment schedules.


1999 ◽  
Vol 163 (3) ◽  
pp. 477-486 ◽  
Author(s):  
AI Turner ◽  
PH Hemsworth ◽  
BJ Canny ◽  
AJ Tilbrook

Prolonged stress is known to impair reproduction. It has been proposed that reproduction will also be impaired when a severe acute stress occurs during a period of elevated plasma concentrations of oestradiol, such as during the follicular phase of the oestrous cycle. In this experiment, we hypothesised that repeated acute and sustained elevation of cortisol would suppress the secretion of LH in ovariectomised pigs and that these effects would be enhanced in the presence of oestradiol negative feedback. Cortisol (or vehicle) was administered 12 hourly to ovariectomised pigs (n=6/treatment) for 8 days in the absence of oestradiol treatment and for a further 8 days during treatment with oestradiol. Vehicle was administered to 'control' pigs, 10 or 20 mg cortisol was administered i.v. to pigs to produce 'repeated acute' elevation of cortisol and 250 mg cortisol was administered i.m. to pigs to give a 'sustained' elevation of cortisol. Both before and during treatment with oestradiol, plasma concentrations of LH were monitored on the day before treatment, on the 4th and 8th days of treatment and following an i.v. injection of GnRH at the end of the 8th day of treatment. The repeated acute elevation of cortisol did not impair any parameters of LH secretion (i.e. mean plasma concentrations of LH, pulse amplitude or frequency, pre-LH pulse nadir or the LH response to GnRH) in the absence or in the presence of oestradiol. In contrast, when the elevation of cortisol was sustained, the mean plasma concentrations of LH and the pre-LH pulse nadir were significantly (P<0.05) lower on the 8th day of treatment than on the day before treatment and on the 4th day of treatment. Nevertheless, no other parameters of LH secretion were affected and these effects only occurred in the absence (not in the presence) of oestradiol. In conclusion, cortisol needed to be elevated for more than 4 days to impair the secretion of LH, and oestradiol did not enhance the impact of cortisol on LH secretion in ovariectomised pigs.


2020 ◽  
Vol 12 (01) ◽  
pp. e52-e56 ◽  
Author(s):  
Sunny B. Patel ◽  
Lisa D. Kelly

Abstract Background Despite the frequency of medical students' participation in ophthalmology clerkships away from their home institution, the impact and benefit of these clerkships have remained uninvestigated. To date, no study has focused specifically on medical student perspectives of away ophthalmology clerkships. Objective The purpose of the study was to evaluate the medical students' perspectives on and experience with away rotations in ophthalmology, and assess their effect on residency Match outcomes. Methods An anonymous, original, online survey was designed and distributed to applicants of the 2015 to 2018 ophthalmology Match cycles. Results A total of 69 responses from nine medical institutions were collected (62% response rate). Forty-one respondents (59%) chose to perform at least one away rotation. Among away rotators, the mean number performed was 1.44. Thirty-seven away rotators (90%) reported receiving an interview from at least one host institution they visited. The average estimated cost of an away rotation was ∼1,709 U.S. dollars. With a 95.7% overall match rate among the respondents, no statistically significant difference was seen in match rates between away rotators and nonaway rotators (p = 0.564). Among the away rotators, the mean position on their rank order list matched was 2.34, while the nonaway rotators matched at a mean position of 2.13 (p = 0.383). Conclusion No association between away participation and success in the San Francisco Match was observed in this study. However, study participants did experience non-Match-related benefits from away elective participation.


1992 ◽  
Vol 133 (1) ◽  
pp. 75-85 ◽  
Author(s):  
M.-P. Laurentie ◽  
R. Garcia-Villar ◽  
P.-L. Toutain ◽  
J. Pelletier

ABSTRACT The purpose of the present experiment was to characterize LH secretion pulsatility in rams by analysing the instantaneous secretion rate profile obtained by deconvoluting the plasma concentration profile. Plasma LH concentration profiles were obtained by collecting blood samples every 6 min for 24 h during two different sessions separated by an interval of 15 days. Individual kinetic parameters of ovine LH (oLH) were determined following i.v. injection of oLH. By deconvoluting the plasma concentration profile, it was shown that a pulse has an effective duration of only 20·41±7·69 (s.d.) min whereas the mean duration estimated from measurement of plasma concentrations was 61·00 ± 15·16 min. The number of pulses was similar before and after deconvolution (7·80±1·99 vs 9·70 ± 3·44 pulses/24 h respectively). Using deconvolution the calculated production rate was 2·26 ± 0·94 μg/kg per 24 h, about 50% of this production being located in the pulses. Statistical analysis of pulsatility revealed that pulse occurrence was a non-periodic event and that the amplitude of LH pulses and the associated amount of LH released were correlated with the duration of the preceding quiescence period, but had no statistically significant influence on the duration of the following quiescence period. Journal of Endocrinology (1992) 133, 75–85


2017 ◽  
Vol 6 (7) ◽  
pp. 500-509 ◽  
Author(s):  
Ferdinand Roelfsema ◽  
Diana van Heemst ◽  
Ali Iranmanesh ◽  
Paul Takahashi ◽  
Rebecca Yang ◽  
...  

Context Studies on 24-h cortisol secretion are rare. The impact of sex, age and adiposity on cortisol levels, often restricted to one or a few samples, are well recognized, but conflicting. Objective To investigate cortisol dynamics in 143 healthy men and women, spanning 7 decades and with a 2-fold body mass index (BMI) range with different analytic tools. Setting Clinical Research Unit. Design Cortisol concentrations in 10-min samples collected for 24 h. Outcomes were mean levels, deconvolution parameters, approximate entropy (ApEn, regularity statistic) and 24-h rhythms. Results Total 24-h cortisol secretion rates estimated by deconvolution analysis were sex, age and BMI independent. Mean 24-h cortisol concentrations were lower in premenopausal women than those in men of comparable age (176 ± 8.2 vs 217 ± 9.4 nmol/L, P = 0.02), but not in subjects older than 50 years. This was due to lower daytime levels in women, albeit similar in the quiescent overnight period. Aging increased mean cortisol by 10 nmol/L per decade during the quiescent secretory phase and advanced the acrophase of the diurnal rhythm by 24 min/decade. However, total 24-h cortisol secretion rates estimated by deconvolution analysis were sex, age and BMI independent. ApEn of 24-h profiles was higher (more random) in premenopausal women than those in men (1.048 ± 0.025 vs 0.933 ± 0.023, P = 0.001), but not in subjects older than 50 years. ApEn peaked during the daytime. Conclusion Sex and age jointly determine the 24-h cortisol secretory profile. Sex effects are largely restricted to age <50 years, whereas age effects elevate concentrations in the late evening and early night and advance the timing of the peak diurnal rhythm.


1997 ◽  
Vol 161 ◽  
pp. 197-201 ◽  
Author(s):  
Duncan Steel

AbstractWhilst lithopanspermia depends upon massive impacts occurring at a speed above some limit, the intact delivery of organic chemicals or other volatiles to a planet requires the impact speed to be below some other limit such that a significant fraction of that material escapes destruction. Thus the two opposite ends of the impact speed distributions are the regions of interest in the bioastronomical context, whereas much modelling work on impacts delivers, or makes use of, only the mean speed. Here the probability distributions of impact speeds upon Mars are calculated for (i) the orbital distribution of known asteroids; and (ii) the expected distribution of near-parabolic cometary orbits. It is found that cometary impacts are far more likely to eject rocks from Mars (over 99 percent of the cometary impacts are at speeds above 20 km/sec, but at most 5 percent of the asteroidal impacts); paradoxically, the objects impacting at speeds low enough to make organic/volatile survival possible (the asteroids) are those which are depleted in such species.


Author(s):  
Julie L. Wambaugh ◽  
Lydia Kallhoff ◽  
Christina Nessler

Purpose This study was designed to examine the association of dosage and effects of Sound Production Treatment (SPT) for acquired apraxia of speech. Method Treatment logs and probe data from 20 speakers with apraxia of speech and aphasia were submitted to a retrospective analysis. The number of treatment sessions and teaching episodes was examined relative to (a) change in articulation accuracy above baseline performance, (b) mastery of production, and (c) maintenance. The impact of practice schedule (SPT-Blocked vs. SPT-Random) was also examined. Results The average number of treatment sessions conducted prior to change was 5.4 for SPT-Blocked and 3.9 for SPT-Random. The mean number of teaching episodes preceding change was 334 for SPT-Blocked and 179 for SPT-Random. Mastery occurred within an average of 13.7 sessions (1,252 teaching episodes) and 12.4 sessions (1,082 teaching episodes) for SPT-Blocked and SPT-Random, respectively. Comparisons of dosage metric values across practice schedules did not reveal substantial differences. Significant negative correlations were found between follow-up probe performance and the dosage metrics. Conclusions Only a few treatment sessions were needed to achieve initial positive changes in articulation, with mastery occurring within 12–14 sessions for the majority of participants. Earlier occurrence of change or mastery was associated with better follow-up performance. Supplemental Material https://doi.org/10.23641/asha.12592190


2013 ◽  
Vol 12 (2) ◽  
pp. 119-125

The present study concerns the impact of a change in the rainfall regime on surface and groundwater resources in an experimental watershed. The research is conducted in a gauged mountainous watershed (15.18 km2) that is located on the eastern side of Penteli Mountain, in the prefecture of Attica, Greece and the study period concerns the years from 2003 to 2008. The decrease in the annual rainfall depth during the last two hydrological years 2006-2007, 2007-2008 is 10% and 35%, respectively, in relation to the average of the previous years. In addition, the monthly distribution of rainfall is characterized by a distinct decrease in winter rainfall volume. The field measurements show that this change in rainfall conditions has a direct impact on the surface runoff of the watershed, as well as on the groundwater reserves. The mean annual runoff in the last two hydrological years has decreased by 56% and 75% in relation to the average of the previous years. Moreover, the groundwater level follows a declining trend and has dropped significantly in the last two years.


2018 ◽  
Author(s):  
Natalia Banasik ◽  
Dariusz Jemielniak ◽  
Wojciech P?dzich

BACKGROUND There have been mixed results of the studies checking whether prayers do actually extend the life duration of the people prayed for. Most studies on the topic included a small number of prayers and most of them focused on people already struggling with a medical condition. Intercessory prayer’s influence on health is of scholarly interest, yet it is unclear if its effect may be dependent on the number of prayers for a named individual received per annum. OBJECTIVE We sought to examine if there is a noticeable increased longevity effect of intercessory prayer for a named individual’s well-being, if he receives a very high number of prayers per annum for an extended period. METHODS We retrieved and conducted a statistical analysis of the data about the length of life for 857 Roman Catholic bishops, 500 Catholic priests, and 3038 male academics from the US, France, Italy, Poland, Brazil, and Mexico. We obtained information for these individuals who died between 1988 and 2018 from Wikidata, and conducted an observational cohort study. Bishops were chosen for the study, as they receive millions of individual prayers for well being, according to conservative estimates. RESULTS There was a main effect for occupation F(2, 4391) = 4.07, p = .017, ηp 2 = .002, with pairwise comparisons indicating significant differences between the mean life duration of bishops (M=30489) and of priests (M=29894), but none between the academic teachers (M=30147) and either of the other groups. A comparison analysis between bishops from the largest and the smallest dioceses showed no significant difference t(67.31)=1.61, p = .11. Our main outcome measure is covariance of the mean length of life in each of the categories: bishops, priests, academic teachers, controlled for nationality. CONCLUSIONS The first analysis proved that bishops live longer than priests, but due to a marginal effect size this result should be treated with caution. No difference was found between the mean length of life of bishops from the largest and the smallest dioceses. We found no difference between bishops and male academics. These results show that the impact of intercessory prayers on longevity is not observable.


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