Circadian variations in plasma LH and FSH in juvenile and adult male mice

Experiments were performed to ascertain circadian fluctuations in plasma levels of LH and FSH in juvenile and adult male mice. Animals under natural lighting (11 h day/13 h night) were killed at 1-hour intervals over a 24-hour period. There were large variations in plasma LH concentrations between animals sacrificed within each killing period. Baseline LH levels (values lower than 60 ng/ml) showed a significant 24-hour periodicity in adult males. FSH concentrations exhibited significant diurnal variations in juvenile and adult males. There was significant influence of age on the temporal pattern and 24-hour mean plasma hormone levels.     

Diurnal beta-endorphin changes in human cerebrospinal fluid

Plasma and cerebrospinal fluid (CSF) beta-endorphin levels were determined by a RIA method in seven hydrocephalic male patients. The samples were simultaneously collected every two hours from 8 AM to 12 midnight and every hour from 1 AM to 7 AM. In both plasma and CSF beta-endorphin levels showed significant time-related variations during the 24 hour period. These results suggest the existence of diurnal CSF beta-endorphin variations analogous to those observed in plasma.     

Circadian variations in concentrations of plasma thyroxine and triiodothyronine in man.

The plasma concentrations of thyroxine (T4), triiodothyronine (T3), and total protein (Pr) were measured at 2-h intervals in 8 male subjects during two 24-h periods. Plasma T4 and T3 levels varied significantly during the day. T4 values were highest at 0900 hours and thereafter declined rapidly reaching lowest levels at 1500-1700 hours (mean decrement, 13.2% of 0.00-hour value). Plasma T3 was highest at 0900 hours and lowest at 1700-1900 hours (mean decrement, 16.7% of 0900-hour value). Fluctuations observed in Pr were not significant. Variations in plasma T4 and T3 appeared concordant with respect to time, since no significant variation was detected in T3:T4 plasma concentration ratios. In view of previous studies that have demonstrated circadian variations in the binding of thyroid hormones by plasma proteins, it is suggested that the observed temporal variations in plasma concentrations of T3 and T4 reflect parallel changes in the capacity or affinity of specific plasma binding proteins of these iodothyronines.     

Circadian variations of plasma renin activity (PRA), aldosterone and electrolyte concentrations in plasma in pregnant and non-pregnant goats

The aim of this study was to estimate and analyse circadian variations of the renin-angiotensin-aldosterone system (RAA) activity in blood of goats and the influence of late pregnancy on the circadian variations of RAA system. The study was carried out on a group of 17 non-pregnant and 9 pregnant goats. The animals were kept in uniform environmental conditions, (9 h light/15 h darkness). Blood samples were collected seven times over a period of 24 h, every 4 h. Plasma renin activity (PRA), plasma aldosterone (PA), sodium, potassium and chloride concentrations were determined. PRA and PA of both groups changed during 24 h, with the highest values in the dark phase and with higher RAA system activity (especially during the night) in the pregnant goats. In the non-pregnant goats, no circadian changes in PRA and PA were observed. The circadian changes in PRA and PA found in pregnant goats had acrophases at 06:27 h and 01:13 h, respectively. Plasma electrolyte concentrations in both groups of goats also changed during 24 h. These results suggest that circadian changes of potassium concentration in plasma of goats during late pregnancy may be one of the main factors affecting the RAA system.     

A diurnal plasma vasopressin rhythm in rats

The purpose of this paper was to determine whether there is a diurnal plasma arginine vasopressin (AVP) rhythm in rats. Using an AVP radioimmunoassay, plasma AVP levels were determined at frequent intervals throughout a 24-hour period in adult male rats. Our data revealed a diurnal rhythm in plasma AVP levels, with mid-afternoon and early evening levels significantly greater than those in the morning and late evening.     

Ultradian, circadian and seasonal variations of plasma progesterone and LH concentrations during the luteal phase

The circadian variations in plasma progesterone (P) and LH concentrations were investigated in six women, aged 23-40 years. All were studied in the mid-luteal phase (7 +/- 2 days after LH mid-cycle surge). Experiments were conducted in autumn and in spring. Blood samples were obtained every 15 min for 24 hr. Plasma P and LH concentrations were measured by RIA. Each subject's time-series was analysed using three methods; visual inspection (chronogram), spectral analysis to estimate component periods of rhythms (tau) and cosinor analysis to quantify the rhythms parameters. Marked temporal variations in plasma P concentration were observed in each subject. The maximal variations over a 24-hr period, ranged between 13-58.5 mmol/l. Differences related to sampling time were statistically validated by ANOVA (p less than 0.00001). Significant harmonic periods were detected by spectral analysis but differed among subjects. In all subjects but one, a circadian rhythm was detected. The acrophase location was similar (about 0700 hr) in the four subjects studied in autumn, but ranged from 1940 to 0320 hr in those studied in spring. An ultradian rhythm with tau = 8 hr was also validated in six time-series with similar acrophases (about 0200, 1000, and 1800 hr). Cosinor analysis of pooled data revealed that the 24-hr, 12-hr, and 8-hr rhythms were statistically significant (p = 0.001) in autumn. algebraic sum of these three cosine functions yielded a circadian waveform with peak-times occurring near 0300 and 1130 hr and a trough-time about 2200 hr. In spring, the circadian pattern appeared quite different, and peak-times were found near 0700 and 2000 hr, and trough-times near 0300 and 1500 hr. Furthermore, the 24-hr mean of P was higher in autumn (28.9 +/- 0.4 nmol/l) than in spring (17.2 +/- 0.4 nmol/l), p from ANOVA less than 0.00001. The evidence for a similar circadian LH pattern is not as strong. Seasonal, circadian and ultradian rhythms characterize the physiologic time structure of plasma P concentration in mid-luteal phase.     

Effect of bromocriptine on the control of plasma aldosterone diurnal variation in normal supine man.

In order to investigate the role of prolactin in the control of the circadian rhythm of plasma aldosterone (PA), plasma renin activity (PRA), cortisol (PC), aldosterone and prolactin (PRL) levels were determined in samples at 4-hour intervals from 5 normal supine men over a period of 24 h under basal conditions and subsequently over a period of 24 h during suppression of prolactin release by bromocriptine (CB-154). After suppression of prolactin, statistically signific1nt circadian rhythms in PC and PA have been detected with a moderate decrease of PA concentration, while the PC level remained unalterated. PRA rhythmicity persisted with a significant shift of acrophase and remarkable reduction of plasma levels. Moreover, during CB administration a significant correlation was obtained between PA and PC, while no correlation was detected between PA and PRA. These data are consistent with the following concepts: (a) the prolactin does not play a significant role in the regulation of circadian rhythm and concentration of plasma aldosterone in normal supine men, and (b) bromocriptine induces a remarkable reduction of PRA and a variable decrease in plasma aldosterone, but it does not influence the secretion of cortisol in normal subjects.     

Neurohypophyseal peptide levels in CSF and plasma during passive avoidance behavior in rats

Levels of vasopressin (AVP), oxytocin (OXT), and neurophysin (NP) in CSF and plasma of rats were determined during acquisition and retention of passive avoidance behavior. None of the levels of neurohypophyseal peptides in CSF were changed either during the adaptation period, or during acquisition or the retention of this behavior. Moreover, no differences were found in hormone levels in CSF of the various groups of rats subjected to different shock intensities during the acquisition trial. The marked differences in individual latencies of nonavoiding rats, and the differences in latencies due to a different shock intensity applied during the learning trial were not reflected by changes in CSF hormone levels. Neither AVP nor NP levels in plasma were affected by the different shock intensities applied, when measured at 20 min after the learning trial. In contrast, a decrease in plasma OXT levels was observed after application of a shock intensity of 0.25 mA during the learning trial. During retention of the passive avoidance response plasma levels of AVP, OXT and NP were not different from the levels found in the nonshocked groups. It is suggested that under the conditions used in this study the CSF is apparently not involved in the distribution of neurohypophyseal peptides to their possible sites of behavioral action in the brain.     

Metoclopramide increases plasma but not cerebrospinal fluid vasopressin levels in man: study in hydrocephalic patients.

Arginine vasopressin (AVP) concentrations were determined in plasma and in cerebrospinal fluid (CSF) in 8 adult male patients suffering from hydrocephalus of various etiologies, before and after intravenous administration of 10 mg metoclopramide. Metoclopramide was able to increase the plasma (2.6 +/- 0.2 ng/l in basal conditions and 6.1 +/- 0.6 ng/l at 30 min) but not the CSF AVP levels. The results suggest that the neurons which secrete AVP into the CSF may be functionally different from those secreting into the peripheral circulation.     

Episodic secretion of opioid activity in human plasma and monkey CSF: Evidence for a diurnal rhythm

Using a radioreceptor assay, opioiod activity has been determined in human plasma and monkey CSF at two-hour intervals across a 24-hour period. In both human plasma and monkey CSF, opioid activity showed an episodic secretion and a significant variation over time, suggesting a diurnal rhythm with increased levels in the morning. This rhythm is similar to those of adrenocorticotropin and beta-lipotropin (LPH) and reciprocal to the diurnal rhythm of pain sensitivity.     

The nude rat is established as a model for endocrine studies: regulation of thyroid function and xenotransplantation of a thyroid tumor cell line.

The thyroid physiology of athymic nude rats, rnu/rnu, is characterized and established here as an animal model to study transplanted thyroid tumors. Male rats were catheterized 5 days before experiments were started. The mean thyroid-stimulating-hormone (TSH) plasma concentrations were 2.9 +/- 0.6 ng/ml during infusion of 0.25 ml/h of 0.9% NaCl (n = 12). T3 plasma concentrations were 2.6 +/- 0.4 ng/ml. T4 plasma levels were 22.0 +/- 5.6 micrograms/dl. A bolus of 0.1 mg thyrotropin-releasing hormone (TRH) significantly increased TSH plasma concentrations (P less than or equal to 0.001; from 2.9 +/- 0.6 to 7.8 +/- 1.1 ng/ml, n = 12). No pulsatile TSH secretion was observed in a 2-hour period with blood samples taken every 10 minutes (n = 12) and hourly sampling disclosed no circadian variation of TSH during a 24-hour period (n = 4). Successful xenografting was possible in 12 of 15 cases using a follicular thyroid carcinoma cell line (FTC 133). Measurement of human thyroglobulin (hTg) by a hTg IRMA revealed high levels in rats with functional FTC tumors, whereas no hTg was detected in untransplanted rats or animals with nonfunctional transplants.     

Serial cerebrospinal fluid tryptophan and 5-hydroxy indoleacetic acid concentrations in healthy human subjects

The role of the serotonergic system in the pathogenesis of behavioral disorders such as depression, alcoholism, obsessive-compulsive disorder, and violence is not completely understood. Measurement of the concentration of neurotransmitters and their metabolites in cerebrospinal fluid (CSF) is considered among the most valid, albeit indirect, methods of assessing central nervous system function in man. However, most studies in humans have measured lumbar CSF concentrations only at single time points, thus not taking into account rhythmic or episodic variations in levels of neurotransmitters, precursors, or metabolites. We have continuously sampled lumbar CSF via subarachnoid catheter in 12 healthy volunteers, aged 20-65 years. One ml (every 10 min) CSF samples were collected at a rate of 0.1ml/min for 24-hour (h), and the levels of tryptophan (TRP) and 5-hydroxy indoleacetic acid (5-HIAA) were measured. Variability across all 12 subjects was significantly greater (P < 0.0001) than the variability seen in repeated analysis of a reference CSF sample for both 5-HIAA (32.0% vs 7.9%) and TRP (25.4% vs 7.0%), confirming the presence of significant biological variability during the 24-hr period examined. This variability could not be explained solely by meal related effects. Cosinor analysis of the 24-hr TRP concentrations from all subjects revealed a significant diurnal pattern in CSF TRP levels, whereas the 5-HIAA data were less consistent. These studies indicate that long-term serial CSF sampling reveals diurnal and biological variability not evident in studies based on single CSF samples.     

Effect of aging on 24-hour changes in dopamine and serotonin turnover and amino acid and somatostatin contents of rat corpus striatum

This study examined the 24-hour changes in a number of transmitters in the corpus striatum of young and middle-aged male Wistar rats. The contents of excitatory amino acids (glutamate, aspartate) and inhibitory amino acids (gamma-aminobutyric acid, GABA; taurine, glycine) and of somatostatin were measured in 2-month- and 18- to 20-month-old rats killed at six different time points along the 24-hour cycle. The striatal serotonin and dopamine turnover was also measured. Both young and middle-aged rats showed significant 24-hour variations in striatal glutamate and aspartate contents; only in young rats these variations fitted a cosine function, with acrophase during the first part of rest span. Mesor values of striatal excitatory amino acid contents were lowest in middle-aged rats. Significant 24-hour variations in striatal contents of GABA, taurine, and glycine occurred in young rats, while only striatal GABA exhibited 24-hour changes in middle- aged rats (acrophases during the first part of rest span). For every inhibitory transmitter, the mesor values in middle-aged rats were significantly lower than in young rats. The 24-hour variation of the striatal somatostatin content showed acrophase during the first part of rest span, mesor values and amplitude being lowest in middle-aged rats. Aging rats exhibited significantly higher mesor values of striatal serotonin turnover (34% increase) and lower mesor values of dopamine turnover (69% decrease) than their younger counterparts. Some of the circadian modifications of motor function seen in aging rats could be related to the striatal transmitter changes reported herein.     

Changes in salivary cortisol concentrations during a 24-hour period in dogs.

The purpose of this investigation was to clarify whether salivary cortisol secretion in dogs had a circadian rhythm. Saliva sampling during a 24-hour period was performed in 4 non-consecutive days. Eight adult beagle dogs (4 males and 4 females) were divided into 4 groups, and 2 dogs (1 male and 1 female) were used for each repetition. Saliva samples were taken at 1 h intervals from 9:00 a. m. to 9:00 a. m. of the following day. Salivary cortisol concentrations were determined using enzyme-linked immunosorbent assay. No circadian rhythm was detected for salivary cortisol, and the differences among salivary cortisol concentrations measured every hour were not demonstrated during a 24-hour period in dogs.     

Circadian variations of serotonin in plasma and different brain regions of rats

Most of the physiological processes that take place in the organism follow a circadian rhythm. Serotonin is one of the most important neurotransmitters in our nervous system, and has been strongly implicated in the regulation on the mammalian circadian clock, located in the suprachiasmatic nuclei (SCN). The present study analysed the levels of serotonin over a period of 24 h in the plasma and in different brain regions. The model used was of male Wistar rats, 14 +/- 2 weeks of age (n = 120), maintained under conditions of 12 h light and 12 h dark, and food and water ad libitum. The serotonin levels were measured by ELISA every hour at night (20:00-08:00 h) and every 4 h during the daytime (08:00-20:00 h). Ours results show that the maximum levels of serotonin in plasma were obtained at 09:00 and 22:00 and a minor peak at 01:00 h. In hypothalamus there was a significant peak at 22:00 and two minor peaks at 17:00 and 02:00 h; the same occurred in hippocampus with a significant peak at 21:00, and two secondary peaks at 24:00 and 05:00 h; in cerebellum there were two peaks at 21:00 and 02:00 h, while in striatum and pineal there were peaks at 21:00 h and 23:00, respectively. In conclusion, the higher levels of serotonin were during the phase of darkness, which varies depending on the region in which it is measured.     

家兔发热时脑脊液和血浆中精氨酸加压素含量的变化及禁水的抗热作用

本实验观察了发热家兔脑脊液(CSF)和血浆中精氨酸加压素(AVP)含量的变化及禁水对家兔内毒素(ET)发热效应的影响。实验结果表明:1.隔区注射AVP可明显抑制家兔ET性发热效应;2.发热组家兔CSF和血浆中AVP含量较正常组明显降低;3.禁水可明显对抗家兔ET性发热效应,其抗热作用与CSF和血浆中AVP含量升高有关;4.禁水也可使正常家兔体温水平下移。上述实验结果提示,AVP可能是家兔体内一种内源性退热物质,同时在正常体温调节中也可能发挥一定的作用。     

High-performance liquid chromatographic separation of corticosteroids in plasma of rats. Its application to the determination of the circadian rhythm of 18-hydroxycorticosterone related to aldosterone and corticosterone

An efficient separation of corticosteroids in plasma of rats was obtained by reversed-phase high-performance liquid chromatography (HPLC). Plasma corticosteroid assays with HPLC separation were used to determine the circadian rhythm of 18-hydroxycorticosterone (18-OHB) and its possible relationship to aldosterone or corticosterone in conscious rats under standard conditions (regular diet; 12-hour light and 12-hour dark cycle). Significant circadian rhythms of plasma corticosterone, 18-OHB and aldosterone were observed with peak values at 20.00 h and nadir values at 08.00 h. The mean ratio of plasma 18-OHB to aldosterone during 24 h was 2.4. The circadian rhythm of 18-OHB was also correlated with that of plasma aldosterone or corticosterone.     

Ontogeny of the circadian variation of plasma prolactin in sheep

The ontogeny of circadian rhythms is unknown. The newborn sheep has a circadian rhythm of temperature; to study the ontogeny of other rhythms, we examined the 24-h variation of plasma prolactin concentration in fetal and newborn sheep. To this effect, we measured plasma prolactin concentration in chronically catheterized fetuses (n = 7) and in newborn lambs raised under short day nycthemeral (12 light:12 dark, n = 13) or constant light conditions (n = 5). Indwelling catheters were implanted into the jugular vein and carotid artery of late gestation fetuses (0.9 gestation) and newborns (5-29 days old). Experiments were performed 4 or more days after surgery. Lambs were kept in a canvas sling and were fed cow's milk either by mouth or through a nasogastric catheter at established time intervals. Haematocrit, pH, and blood gases were measured before and after the experiments in all cases and remained within normal values. Lights were on and room temperature was maintained constant during the whole experiment. Samples were obtained every 1-2 h for 24 h in fetuses and newborn lambs under nycthemeral conditions and every hour for 48 h in newborn lambs kept under constant light. Plasma prolactin was measured by radioimmunoassay. The presence of a 24 h rhythm was determined by Cosinor analysis. Fetuses, aged 129 +/- 6 days (SD) n = 7, showed a variation in plasma prolactin concentration with a period of 24 h that fits the equation: plasma prolactin (ng ml-1) = 97.0 + 15.4 cos 15 (t-23.0), P = 0.035.(ABSTRACT TRUNCATED AT 250 WORDS)     

Time-related neuroendocrine manifestations of puberty: a combined clinical and experimental approach extracted from the 4th Belgian Endocrine Society lecture

The neuroendocrine manifestations of puberty converge on changes in GnRH secretion. Their appraisal through the assay of GnRH-like material in 24-hour urine extracts shows an increased excretion of this material in the late prepubertal period. The most striking pubertal changes in GnRH secretion occur on a circadian and ultradian basis. In man, they can be evaluated only indirectly. The circadian variations in LH and FSH secretion characteristic of puberty may be observed in timed fractions of 24-hour urine with some delay when compared to the variations of plasma levels. Studies on the frequency of pulsatile LH secretion and during chronic intermittent administration of GnRH support the existence of an increased frequency of GnRH secretory episodes at puberty. LH response to synthetic GnRH is directly related to the frequency of stimulation by endogenous GnRH pulses and provides a very useful index of neuroendocrine maturation in patients with delayed or precocious puberty. A direct evaluation of pulsatile GnRH secretion is possible using the rat hypothalamus in vitro. In these experimental conditions, the frequency of pulsatile GnRH release increases during very early stages of sexual maturation in the male rat. GnRH itself and beta-endorphin are inhibitory regulators of GnRH secretion in vitro and may participate in the mechanisms restraining the pulse-generating machinery in the hypothalamus before puberty.     

Circadian variations in plasma concentrations of melatonin and prolactin during breeding and non-breeding seasons in yak (Poephagus grunniens L.)

Circadian variations of plasma melatonin and prolactin concentrations were determined during breeding as well as non-breeding seasons in yak. Blood samples (5 ml) were collected during different phases of estrous cycle, viz. early (0-6 days), mid (7-12 days) and late luteal (13-19 days) at 2 h interval for 24 h from eight yaks during one breeding month (November); the same yaks were bled at 2 h interval during one non-breeding month (February) for 24 h. Plasma melatonin concentrations rose sharply (P < 0.01) after sunset to record peak concentrations between midnight and 2 a.m. declining sharply thereafter in both breeding as well as non-breeding seasons. Basal melatonin concentrations were recorded between 0600 and 1600 h. Stage of luteal phase did not influence the diurnal hormone change (P < 0.01). In the breeding season, mean plasma prolactin concentrations displayed circadian variations with maximum value at 0400 h (41.22+ /- 1.5 ng/ml) and minimum at 1400 h (12.0 +/- 4.02 ng/ml). In the non-breeding season plasma prolactin concentrations showed circadian variation with maximum value at 0000 h (59.9 +/- 10.5 ng/ml) and minimum at 1200 h (32.13 +/- 3.2 ng/ml). A positive correlation in breeding (r = 0.75) and in non-breeding season (r = 0.65) between circadian changes in mean plasma prolactin and melatonin concentrations were seen. Circadian changes of mean plasma melatonin concentrations during breeding and non-breeding seasons were not different (P > 0.05). However, mean plasma prolactin concentrations were found to be higher (P < 0.01) in the non-breeding season. Three conclusions were drawn from the study: (i) melatonin and prolactin concentrations followed a circadian pattern of secretion (ii) melatonin and prolactin secretion may be closely interrelated and (iii) higher prolactin concentrations during the non-breeding season could be due to nutritional and environmental stress and hence might be contributing to lack of cyclicity.