Diurnal changes in the plasma concentrations of LH and hypothalamic contents of LHRH-I and LHRH-II in the domestic hen

1991 ◽  
Vol 130 (3) ◽  
pp. 457-462 ◽  
Author(s):  
S. C. Wilson ◽  
R. T. Gladwell ◽  
F. J. Cunningham

ABSTRACT Diurnal changes of LH secretion in sexually immature hens of 9, 11, 13 and 15 weeks of age consisted of 25–40% increases in the mean concentrations of LH in plasma between 15.00 and 18.00 h, i.e. between 2 h before and 1 h after the onset of darkness. During this time there was a tendency for the mean contents of LHRH-I in the anterior hypothalamus and posterior hypothalamus to increase by 21–74% and 20–56% respectively. In hens of 9 and 15 weeks, diurnal changes in the plasma concentration of LH closely paralleled those of LHRH-I content in the posterior hypothalamus. In contrast, the diurnal rhythm of LH secretion in hens of 11 and 13 weeks was more marked and plasma concentrations of LH continued to rise steeply between 18.00 and 21.00 h, i.e. between 1 and 4 h after the onset of darkness. At 11 weeks, this was associated with a reduction (P<0·01) in the contents of LHRH-I and LHRH-II, particularly in the anterior hypothalamus. In laying hens, a diurnal decline (P<0·01) in the plasma concentration of LH between 1 and 4 h after the onset of darkness was preceded by a fall (P<0·05) in the content of LHRH-I in the posterior hypothalamus and in the total hypothalamic content of LHRH-II (P<0·01). In all groups of hens, irrespective of the times of day at which tissue was taken, significant (P<0·05–<0·001) correlations between the contents of LHRH-I and LHRH-II in the anterior hypothalamus were observed. It is concluded that a diurnal rhythm of release of LHRH-I may drive the diurnal rhythm of LH secretion. Thus, in sexually immature hens of 9 and 15 weeks and laying hens in which diurnal changes in plasma LH were small there were parallel changes in the content of LHRH-I in the posterior hypothalamus. However, where the plasma concentration of LH was increased substantially, as at 11 weeks, there was a decline in the hypothalamic contents of LHRH-I. A simultaneous fall in the hypothalamic content of LHRH-II raises the possibility of a causal relationship between the activities of LHRH-II, LHRH-I and the release of LH. Journal of Endocrinology (1991) 130, 457–462

1990 ◽  
Vol 127 (3) ◽  
pp. 487-496 ◽  
Author(s):  
S. C. Wilson ◽  
R. A. Chairil ◽  
F. J. Cunningham ◽  
R. T. Gladwell

ABSTRACT The contents of LHRH-I and -II in the anterior hypothalamus and posterior hypothalamus (including the mediobasal hypothalamus and median eminence) were measured at 90, 180 and 360 min after the i.m. injection of laying hens with progesterone. Whilst no changes were observed in the content of LHRH-I in the anterior hypothalamus, LHRH-I in the posterior hypothalamus tended to fall at 90 and 180 min after injection of progesterone in hens maintained on 16 h light:8 h darkness (16L:8D) and 8L:16D respectively. Pretreatment of laying hens with tamoxifen significantly increased the hypothalamic contents of LHRH-I and -II, raised the basal plasma concentration of LH and modified the LH response to progesterone injection. In hens in which tamoxifen prevented an increase in the plasma concentration of LH after progesterone injection, the content of LHRH-I in the posterior hypothalamus remained unchanged. In contrast, in hens in which progesterone stimulated a steep increase in LH within 90 min, there was a pronounced and significant fall in LHRH-I content of the posterior hypothalamus. No change in the hypothalamic content of LHRH-II was observed during the progesterone-induced surge of LH until plasma concentrations had attained maximal values or started to decline. Then, in hens maintained on 16L:8D, a significant fall in the content of LHRH-II in the anterior hypothalamus was found at both 180 and 360 min after injection with progesterone. Tests in vitro and in vivo of the responsiveness of the pituitary gland to synthetic LHRH-I and -II revealed no change at 90 min after injection of laying hens with progesterone, when plasma concentrations of LH were increasing, but a pronounced reduction when plasma LH concentrations were maximal or falling. These results suggest that LHRH-I mediates in the progesterone-induced increase in the plasma concentration of LH. Although the subsequent decline in plasma LH was associated with a reduced responsiveness of the pituitary gland to LHRH, a significant correlation between the contents of LHRH-I and -II in the anterior hypothalamus and a fall in the hypothalamic content of LHRH-II when plasma LH was maximal or declining allows the possibility of an involvement of this peptide in the neuroendocrine events preceding ovulation. Journal of Endocrinology (1990) 127, 487–496


1984 ◽  
Vol 101 (3) ◽  
pp. 299-304 ◽  
Author(s):  
S. C. Wilson ◽  
R. C. Jennings ◽  
F. J. Cunningham

ABSTRACT When diurnal changes in the plasma concentrations of corticosterone and LH were compared at various times during sexual development a diurnal rhythm in the secretion of corticosterone was most pronounced at 4·5 weeks of age in hens maintained on a schedule of 8 h light: 16 h darkness (8L: 16D) and at 8·5 weeks of age in hens maintained on 16L: 8D. At these ages the phase-angle of the rhythm in relation to the onset of darkness was 3 h earlier than had been observed in previous studies of the adult hen. The characteristics of the corticosterone rhythm changed during sexual development and diurnal changes were no longer evident in hens at 17 weeks of age at a time when prepubertal plasma concentrations of LH were maximal. However, there was a tendency for plasma concentrations of corticosterone to fluctuate diurnally in hens studied at less than 10 days before the onset of lay although not to the same extent as has previously been observed in the adult hen. This period of development was associated with a pronounced increase in the plasma concentration of progesterone. An increase in the plasma concentration of LH at the onset of darkness was observed at all ages in hens maintained on either photoschedule. In hens of 4·5–15 weeks of age maintained on 16L:8D or 8L:16D this increase in the plasma concentration of LH was sustained during the first 5 or 8–11 h of darkness respectively but at 17 weeks of age only a transient increase in LH was seen at the onset of darkness. Plasma concentrations of LH in samples of plasma taken at intervals of between 3 days and 2 weeks throughout sexual development were, until 18–19 weeks, consistently higher in hens maintained on a photoschedule of 16L:8D than on 8L: 16D. J. Endocr. (1984) 101, 299–304


1990 ◽  
Vol 125 (1) ◽  
pp. 139-146 ◽  
Author(s):  
S. C. Wilson ◽  
R. T. Gladwell ◽  
F. J. Cunningham

ABSTRACT Changes in the hypothalamic contents of LHRH-I and LHRH-II were determined in intact and castrated cockerels injected i.m. with gonadal steroids or tamoxifen. An increase in the plasma concentration of LH after castration was accompanied by a significant increase in the content of LHRH-I in the posterior hypothalamus (including the mediobasal hypothalamus and median eminence) which was reversed by oestradiol benzoate given on days 14 and 15 after castration. Under similar circumstances, testosterone propionate did not modify the hypothalamic content of LHRH-I, even though both steroids reduced the plasma concentrations of LH to levels below those of intact cockerels. Treatment of intact cockerels with oestradiol benzoate significantly increased the content of LHRH-I in the posterior hypothalamus, whilst testosterone propionate was again without effect. Tamoxifen significantly raised the plasma concentration of LH in intact cockerels and partially antagonized the suppressive effect of oestradiol benzoate and testosterone on LH secretion in castrated cockerels. However, an anti-oestrogenic effect of tamoxifen on the hypothalamic content of LHRH-I was not demonstrated. There was no evidence of any changes in the hypothalamic content of LHRH-II after castration, with or without gonadal steroid replacement. A change in the hypothalamic content of LHRH-I in response to manipulation of the steroid environment would imply an involvement of this peptide in the mechanism by which gonadal steroids regulate the release of LH. The absence of changes in the hypothalamic content of LHRH-II in the same circumstances suggest that it is not directly involved in the control of LH secretion by the gonadal steroid negative feedback loop. Journal of Endocrinology (1990) 125, 139–146


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


2015 ◽  
Vol 59 (6) ◽  
pp. 3240-3245 ◽  
Author(s):  
Kanokrat Rungtivasuwan ◽  
Anchalee Avihingsanon ◽  
Narukjaporn Thammajaruk ◽  
Siwaporn Mitruk ◽  
David M. Burger ◽  
...  

ABSTRACTTenofovir (TFV) is eliminated by renal excretion, which is mediated through multidrug-resistant protein 2 (MRP2) and MRP4, encoded byABCC2andABCC4, respectively. Genetic polymorphisms of these transporters may affect the plasma concentrations of tenofovir. Therefore, the aim of this study was to investigate the influence of genetic and nongenetic factors on tenofovir plasma concentrations. A cross-sectional study was performed in Thai HIV-infected patients aged ≥18 years who had been receiving tenofovir disoproxil fumarate at 300 mg once daily for at least 6 months. A middose tenofovir plasma concentration was obtained. Multivariate analysis was performed to investigate whether there was an association between tenofovir plasma concentrations and demographic data, including age, sex, body weight, estimated glomerular filtration rate (eGFR), hepatitis B virus coinfection, hepatitis C virus coinfection, duration of tenofovir treatment, concomitant use of ritonavir-boosted protease inhibitors, and polymorphisms ofABCC2andABCC4. A total of 150 Thai HIV-infected patients were included. The mean age of the patients was 43.9 ± 7.2 years. The mean tenofovir plasma concentration was 100.3 ± 52.7 ng/ml. In multivariate analysis, a low body weight, a low eGFR, the concomitant use of ritonavir-boosted protease inhibitors, and theABCC44131T → G variation (genotype TG or GG) were independently associated with higher tenofovir plasma concentrations. After adjusting for weight, eGFR, and the concomitant use of ritonavir-boosted protease inhibitors, a 30% increase in the mean tenofovir plasma concentration was observed in patients having theABCC44131 TG or GG genotype. Both genetic and nongenetic factors affect tenofovir plasma concentrations. These factors should be considered when adjusting tenofovir dosage regimens to ensure the efficacy and safety of a drug. (This study has been registered at ClinicalTrials.gov under registration no. NCT01138241.)


2019 ◽  
Vol 75 (3) ◽  
pp. 726-729
Author(s):  
Tony Lai ◽  
Jan-Willem Alffenaar ◽  
Alison Kesson ◽  
Sushil Bandodkar ◽  
Jason A Roberts

Abstract Background Posaconazole is a broad-spectrum antifungal that is not licensed for use in children &lt;13 years of age. Despite this and by necessity, it is used extensively in paediatric hospitals for prophylaxis of invasive fungal disease. Objectives To determine whether initial prophylactic dosing recommendations attain a posaconazole plasma concentration of ≥700 ng/mL in immunocompromised children &lt;13 years of age. Patients and methods We performed a retrospective study of immunocompromised children &lt;13 years of age receiving posaconazole suspension prophylaxis at a starting dose of 5 mg/kg every 8 h for ≥7 days and who had a posaconazole concentration measured after ≥7 days. Posaconazole plasma concentrations and rate of breakthrough infection were recorded. Results A total of 70 patients were included with a median age of 5 years (range 3 months to 12 years). The mean posaconazole plasma concentration was 783.4 ng/mL (IQR 428.3–980 ng/mL) and the percentage of patients with a posaconazole plasma concentration ≥700ng/mL was 47.9%. Patients who were on a proton pump inhibitor, a histamine H2 antagonist or metoclopramide, had mucositis or were enterally fed had a lower posaconazole plasma concentration compared with patients without these co-administered drugs/mucositis/enteral feeding (542.3 versus 1069.8 ng/mL; P&lt;0.001). The breakthrough invasive fungal infection rate was 4.3% (3/70). Conclusions The studied 5 mg/kg posaconazole suspension every 8 h resulted in target concentrations in only 47.9% of patients and further studies looking at newer posaconazole formulations are needed.


1990 ◽  
Vol 125 (1) ◽  
pp. 97-102 ◽  
Author(s):  
R. Nowak ◽  
I. R. Young ◽  
I. C. McMillen

ABSTRACT We have monitored the 24-h profiles of plasma melatonin concentrations between birth and 10 weeks of age, in lambs which were delivered to, and suckled, either pineal-intact (control group) or pinealectomized (pinealectomized group) ewes. Between 0 and 2 weeks of age, plasma concentrations of melatonin in lambs suckling either intact or pinealectomized ewes were highest at 01.00 h. At this age, however, there was no significant difference in the mean plasma concentrations of melatonin between the entire dark and light phases in lambs in either the control group (dark, 39·7 ± 6·0 (s.e.m.) pmol/l; light, 39·5 ± 8·1 pmol/l) or the pinealectomized group (dark, 79·8 ± 43·3 pmol/l; light, 60·9 ±8·7 pmol/l). Between 3 and 4 weeks of age, however, a diurnal rhythm in plasma melatonin concentrations was clearly present in the lambs in both the control and pinealectomized groups (control group: dark, 164·1 ± 5·6 pmol/l; light 26·2 ± 2·5 pmol/l; pinealectomized group: dark, 52·7± 8·0 pmol/l; light, 19·1 ± 5·3 pmol/l; P<0·001). Between 3 and 10 weeks of age, plasma concentrations of melatonin in the dark phase were significantly (P<0·05) lower in the lambs suckling pinealectomized ewes than in the control group. In both the control lambs and lambs suckling pinealectomized ewes, the mean plasma concentrations of melatonin in the dark and light phases increased significantly (P<0·05) between 3 and 6 weeks after birth. In conclusion, we have demonstrated that a clear diurnal plasma rhythm in melatonin concentrations does not emerge until 3–4 weeks of age in lambs suckling either pinealectomized or intact ewes. We have also measured lower melatonin concentrations during the dark phase in lambs suckling pinealectomized ewes when compared with lambs suckling pineal-intact ewes between 3 and 10 weeks of age. Journal of Endocrinology (1990) 125, 97–102


1996 ◽  
Vol 84 (2) ◽  
pp. 348-353. ◽  
Author(s):  
M. F. Levine ◽  
J. Sarner ◽  
J. Lerman ◽  
P. Davis ◽  
N. Sikich ◽  
...  

Background Sevoflurane is degraded in vivo in adults yielding plasma concentrations of inorganic fluoride [F-] that, in some patients, approach or exceed the 50- micron theoretical threshold for nephrotoxicity. To determine whether the plasma concentration of inorganic fluoride [F-] after 1-5 MAC x h sevoflurane approaches a similar concentration in children, the following study in 120 children scheduled for elective surgery was undertaken. Methods Children were randomly assigned to one of three treatment groups before induction of anesthesia: group 1 received sevoflurane in air/oxygen 30% (n = 40), group 2 received sevoflurane in 70% N2O/30% O2 (n = 40), and group 3 received halothane in 70% N2O/30% O2 (n = 40). Mapleson D or F circuits with fresh gas flows between 3 and 61/min were used Whole blood was collected at induction and termination of anesthesia and at 1, 4, 6, 12, and 18 or 24 h postoperatively for determination of the [F-]. Plasma urea and creatinine concentrations were determined at induction of anesthesia and 18 or 24 h postoperatively. Results The mean (+/- SD) duration of sevoflurane anesthesia, 2.7 +/- 1.6 MAC x h (range 1.1-8.9 MAC x h), was similar to that of halothane, 2.5 +/- 1.1 MAC x h. The peak [F-] after sevoflurane was recorded at 1 h after termination of the anesthetic in all but three children (whose peak values were recorded between 4 and 6 h postanesthesia). The mean peak [F-] after sevoflurane was 15.8 +/- 4.6 microns. The [F-] decreased to &lt;6.2 microns b 24 h postanesthesia. Both the peak [F-] (r2 = 0.50) and the area under the plasma concentration of inorganic fluoride-time curve (r2 = 0.57) increased in parallel with the MAC x h of sevoflurane. The peak [F-] after halothane, 2.0 +/- 1.2 microns, was significantly less than that after sevoflurane (P&lt;0.00012) and did not correlate with the duration of halothane anesthesia (MAC x h; r2 = 0.007). Plasma urea concentrations decreased 24 h after surgery compared with preoperative values for both anesthetics (P&lt;0.01), whereas plasma creatinine concentrations did not change significantly with either anesthetic. Conclusions It was concluded that, during the 24 h after 2.7 +/- 1.6 MAC x h sevoflurane, the peak recorded [F-] is low (15.8 microns), F- is eliminated rapidly, and children are unlikely to be at risk of nephrotoxicity from high [F-].


1980 ◽  
Vol 8 (5) ◽  
pp. 314-320 ◽  
Author(s):  
Rowan Mary Hillson ◽  
E Boyd ◽  
J Cunningham

Sixty-three patients, fifty-two with acute myocardial infarction and eleven with ischaemic heart disease or non-cardiac chest pain, were given either disopyramide phosphate or placebo, orally, in a randomized double-blind study. Thirty-two patients on disopyramide (twenty-six with acute myocardial infarction) received an initial dose of 300 mg followed by 150 mg six-hourly for 3 days. There was a reduction in the number of patients with cardiac dysrhythmias on the first 3 days following infarction in subjects taking disopyramide as compared with controls. This reduction was not statistically significant. There was a significant reduction in the mean ectopic count per hour in patients taking disopyramide compared with those taking placebo on the second day only (p < 0.005). Urinary retention, dry mouth and jaundice were recorded more frequently in the test group. There were wide ranges of pre-dose plasma concentrations on all 3 days. (Day 1: 1.3 to 7.7 μg per ml. Day 2: 2.5 to 8.9 μg/ml and Day 3: 2.5 to 11.5 μg per ml). The mean plasma concentration of disopyramide was higher but not significantly so, in the treatment group without evidence of dysrhythmias than those with dysrhythmias (3.8 ± S.D. 1.5 μg/ml and 3.0 ± 0.8 μg/ml respectively). The mean plasma level in patients who required anti-emetic therapy was significantly lower than those who did not (2.8 ± 0.8 μg/ml and 3.8 ± 1.9 μg/ml respectively, p < 0.025). The wide range of plasma levels observed is probably due in part to irregular absorption with vomiting after myocardial infarction. If disopyramide is to be used prophylactically following myocardial infarction, a therapeutic plasma level will be achieved quickly in all cases only by giving an intravenous starting dose.


1979 ◽  
Vol 59 (4) ◽  
pp. 655-661 ◽  
Author(s):  
R. J. CHRISTOPHERSON ◽  
H. W. GONYOU ◽  
J. R. THOMPSON

In each of two experiments, plasma concentrations of thyroxine (T4) and triiodothyronine (T3) and the Free Thyopac Index (FTI) were determined, at intervals during winter, in beef steers housed either indoors in a heated barn or in outdoor pens. During experiment 2, a comparison was also made of the effects of four feed intake levels ranging from one to two times maintenance. In both experiments, plasma concentrations of T4 and FTI values were higher in steers kept outdoors than those kept indoors. The highest plasma T4 concentrations and FTI values were recorded in outdoor steers on a maintenance level of feed intake during February when the mean outdoor temperature was −15 °C. Under these circumstances, increasing the level of feed intake to twice maintenance reduced plasma T4 concentrations and FTI values. Level of feed intake had no effect on either plasma T4 or FTI values in steers kept in a heated barn. Plasma T3 concentrations were higher in the outdoor than the indoor steers during experiment 2. Reducing feed intake from twice maintenance to maintenance levels resulted in a decrease in plasma T3 concentrations in steers kept outdoors, but not in those kept indoors in a heated barn. These results indicate that thyroid hormone responses of cattle to cold environments are influenced by the level of feed intake.


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