Circadian variation in plasma melanocyte stimulating hormone activity in the rat.

Non--stress levels of plasma melanocyte stimulating hormone (MSH) and corticosterone were determined at 3-h intervals during controlled light--dark cycles in adult, male rats. Significant 24-h periodicity was demonstrated for both plasma MSH and corticosterone. Whereas plasma MSH values were not as high during the early evening hours as during the early morning hours, plasma corticosterone levels showed a marked rise during the early afternoon and crest values occurred just before the lights off phase of the 24-h light--dark cycle. These results indicate that in the rat, the level of MSH in plasma fluctuates with a low amplitude circadian frequency which is not in phase with that observed for plasma corticosterone.     

Episodic corticosterone secretion in the female rat

Studies conducted in several laboratories have shown primate glucocorticoid secretion to occur episodically. In light of the methodological, as well as physiological importance of this finding, the present study was undertaken to determine whether the rat corticosteroid secretion also occurs episodically. Female rats were outfitted with chronic intravenous cannulas, and 1 week later 200 units of heparin were injected through the implanted cannula and blood samples (0.3-0.4 ml) were collected from each rat every 10 min for 3 h during the morning (06.00-10.00 h) or during the afternoon (16.00-19.00 h) (lights on from 05.00 to 19.00 h). Plasma corticosterone levels in cannulated rats showed fluctuations indicative of episodic secretion. The pattern of plasma corticosterone levels was characterized by periodic rapid increases in hormone concentration during both the morning and afternoon sampling periods; the occurrence of these hormonal fluctuations did not have a characteristic frequency. When the data were grouped to obtain single morning and afternoon values, the AM-PM difference was significant (p < 0.005). Collectively, these data suggest that in the rat, adrenal corticosteroids are secreted episodically.     

A three hours study of the response of plasma corticosterone and of three liver enzymes in rats subjected to stress in the late afternoon or during the morning hours.

In adult male rats kept under controlled illumination (lights on from 6 a.m.--6 p.m.) the existence of higher afternoon values of plasma corticosterone ("B") is reconfirmed. Moreover, plasma "B" increases induced by 400 revolutions in Noble-Collip drums or immobilization for 2.5 h were found substantially less pronounced if stressor application took place at 4 p.m. rather than 8 a.m. so that essentially no difference between morning and afternoon poststress peaks was observed. Also the response to 0.05 mg ACTH i.p. was smaller in the afternoon experiments. Additionally three liver enzymes the activity of which is increased by corticosterone released under conditions of stress were also studied. Higher afternoon activity of liver tyrosine aminotransferase (TAT) and tryptophan pyrrolase (TP) was observed in spite of fasting from 8 a.m. imposed to the animals taking part in the afternoon experiments. The activity of phosphoenolpyruvate carboxykinase (PEPCK) was also increased in the afternoon probably because of the food deprivation. Immobilization-induced increase in the activity of all three enzymes showed a similar blunting as plasma "B" response, so that no differences between morning and afternoon were found in peak poststress values. In conclusion, the low plasma "B" response of rats at a time when the animals begin the active part of their day seems to have important metabolic implications.     

Plasma corticosterone concentrations in the perinatal rat

1. Plasma corticosterone concentrations were determined in the foetal rat during the gestational period from day 18·5 to term and in postnatal rats over the first few hours after delivery. 2. The plasma corticosterone concentrations in foetal rats are as high as six times maternal values at day 19 of gestation and are approximately equal to maternal values from day 20 to term. 3. In postnatal rats the plasma corticosterone concentrations rise 3·5-fold on average within 5hr. of delivery. 4. The results are discussed in relation to the function of adrenal steroids in postnatal liver development.     

The influence of drugs on the kinin-forming system in relation to pregnancy and parturition in the rat.

The duration of normal gestation and parturition in the rat can be changed by treatment with drugs which alter the equilibrium of the kallikrein-kinin system. The kallikrein inhibitor, aprotinin, when given from Days 19-22 of pregnancy prolongs gestation. Treatment with aprotinin from Days 20-22 of pregnancy prolongs the parturient process, as does a single dose given on the morning of Day 22. Kallikrein, when administered from Days 19-22 of pregnancy, results in a prolongation of gestation and abolishes the pre-parturient behaviour ('labour'). Parturition is prolonged and many fetuses are stillborn. Soya bean trypsin inhibitor when given from Days 19-22 of pregnancy delays and prolongs parturition; maternal haemorrhage occurs during birth and many fetuses are born dead or are abandoned at birth. It is suggested that the kallikrein-kinin system plays a functional role in the normal process of parturition in the rat.     

Correlation of ovarian binding of 125I-HCG with formation of cAMP, estradiol and progesterone during pregnancy.

The content of ovarian gonadotropin receptors in rat was found to change during pregnancy. The specific binding of 125I-HCG to ovarian homogenates rose to its maximal values on days 13 and 16. Thereafter, the binding declined as parturition approached. No consistent changes in responsiveness of rat ovary to LH in synthesis of cAMP and estradiol were observed during pregnancy. Plasma estradiol concentration increased on day 16 and remained high throught days 21 and 22. Progesterone levels increase steadily during the first half of pregnancy and then fall, especially sharply on day 21 and 22. The results demonstrate that the secretion of progesterone correlates with gonadotropin receptors during pregnancy.     

The influence of testosterone administration on plasma prolactin levels in the neonatally androgenized (NA) female rat

Neonatally androgenized (NA) female rats were ovariectomized (OVX) as adults and given 1 mg of testosterone propionate/day for 7 days and the plasma prolactin (PRL) pattern compared with NA intact animals and normal OVX animals given estrogen or TP. NA intact animals had elevated basal (morning values) and an attenuated afternoon surge when compared to normal estrogen-treated animals. Testosterone administration to normal animals induced an afternoon surge similar to that of normal estrogen-treated animals but the magnitude of the surge was less. Testosterone given to NA-OVX animals had little effect on either morning or afternoon PRL levels. The results suggest that in the NA rat the brain region involved in the conversion of testosterone to estrogen may be altered by neonatal androgen exposure.     

Diurnal Variation in Glucose Tolerance: Associated Changes in Plasma Insulin,Growth Hormone,and Non-esterified

Oral glucose tolerance tests were performed in the morning and afternoon of separate days on 31 people derived from a normal population sample. Blood sugar levels were higher in the afternoon test from and including 60 minutes after the glucose load. The degree of diurnal variation was similar in men and women, but greater in the older half of the group. It was negatively correlated with the degree of obesity. The plasma insulin response was less at the 30 minute time point in the afternoon, but significantly exceeded the morning values at 120 and 150 minutes after the glucose load. Growth hormone levels were similar in morning and afternoon tests. Fasting non-esterified fatty acid levels were significantly higher before the afternoon test.The relatively impaired glucose tolerance in the afternoon is associated with a delayed insulin response to the glucose load. This seems unlikely to be the sole explanation, however, and increased non-esterified fatty acid metabolism with a consequent decrease in glucose disposal may also contribute.     

Fetal and maternal endocrine changes associated with parturition in the goat

In 4 goats maternal jugular plasma concentrations of progesterone started to decline before labor commenced, but levels remained elevated above basal concentrations throughout parturition. Fetal and maternal plasma concentrations of estrogen rose before and during labor, increasing markedly just prior to fetal delivery. Fetal carotid plasma glucocorticoid concentrations appeared to rise over the 5 days prior to parturition, but a significant increase was only noted during labor. Maternal plasma concentrations of glucocorticoids were significantly lower than fetal plasma concentrations of glucocorticoids. Estradiol-17α was the predominant estrogen in both fetal and maternal plasma, less estrone was detected and apparently little estradiol-17β was present.No good correlation was found between plasma progesterone or estrogen and parturient uterine activity; the latter lasted from 22 to 78 hours, with the most dramatic increase occurring close to delivery. It is probable that other agents are involved in controlling uterine activity during parturition in the goat.     

Plasma gonadotrophins, prolactin and corticosterone concentrations in male mice exposed to high altitude

Groups of sexually-naive male NFR/N mice were maintained at sea level or exposed to simulated altitudes of 18 000 ft (5486 m) or 22 000 ft (6705 m) for 1, 3, 7, 14 or 28 days. Plasma LH concentrations were slightly but not significantly depressed after 1 day of hypoxia. Plasma FSH values were reduced (P < 0.05) after 1, 7, 14 and 28 days of exposure to 22 000 ft when compared to the values in the other groups. Prolactin concentrations fluctuated considerably, but were not uniformly affected by high altitude exposure. Exposure to 18 000 ft resulted in an elevation of plasma corticosterone concentration (P < 0.05) for 3 days, which was followed by a decline to control group values, whereas at 22 000 ft corticosterone levels remained elevated. These findings indicate that plasma LH values are transiently reduced during the initial 24 h of exposure to high altitude and that plasma FSH concentrations are depressed in a sustained manner during severe hypoxia.     

Might cardiac catheterization influence diurnal rhythm of the steroid stress hormones secretion?

Glucocorticoids (GCs) are steroid hormones produced by the adrenal cortex in reaction to stress stimuli. GCs production is not stable over a 24-hour period; the plasma concentration peaks in the morning (approximately upon awakening) and then the plasma levels decrease, reaching the nadir in the evening. In our experiments, the levels of cortisol, cortisone, DHEA and DHEAS were tested in young female pigs (n=23) during heart catheterization at two different day times (in the morning and in the afternoon). The non-parametric Mann-Whitney test for statistical analysis was used. We found only minimal statistical differences in studied markers between the morning and afternoon group (p>0.05). The absence of circadian variation in GCs levels could originate either at an early age of our experimental pigs, or in stressful conditions on the experiment day, or most likely the day before (e.g. social isolation, fasting, transport, and catheterization), respectively. We can conclude there is no difference in the stress load between morning and afternoon experiments, and therefore we can assume the stress load is not a limiting factor for the timing when catheterization should be preferably performed.     

Effect of photoperiod, injection of pentobarbitone sodium or lesion of the suprachiasmatic nucleus on pre-partum decrease of blood progesterone concentrations or time of birth in the rat

In Sprague-Dawley rats kept under 14L:10D (lights on 05:00-19:00 h), parturition occurred during the light phase on Day 23, and the pre-partum decrease in progesterone concentrations was observed between 07:00 and 15:00 h during the light period on Day 22. When the rats were transferred to reversed light-dark regimen (lights on 17:00-07:00 h) on Day 7, the progesterone decrease and parturition still occurred during the light period on Day 21 and 22-23, respectively. However, when rats were kept in constant darkness from Day 7, parturition occurred independently of the time of day between Day 22 and 24. A gradual decline of progesterone concentrations was randomly observed in individual rats. In Wistar rats kept under the usual light-dark regimen, parturitions were biphasic, occurring during the light periods on Day 22 and 23. The progesterone decrease occurred at the usual time even when the lighting regimen was changed only on the day of the expected progesterone decrease. However, treatment with pentobarbitone sodium at 15:00, 19:00 or 21:00 h, but not at 12:00 or 23:00 h, on Day 21 resulted in a delay of progesterone decrease and of parturition. Complete lesion of the suprachiasmatic nucleus on Day 13 or 14 led to advancement and random distribution of the time of birth. These results suggest that the time of parturition and of pre-partum progesterone decrease may be closely associated with an endogenous circadian system, and a luteolytic factor involving the nervous system may be present during a limited period before parturition.     

Closure of the uterine lumen and the plasma membrane transformation do not require blastocyst implantation

Ultrastructural changes in the plasma membrane of uterine epithelial cells in the pseudopregnant rat were examined to determine if these changes resemble those found during normal pregnancy and also to examine if the well-known membrane alterations of early pregnancy are intrinsic to uterine epithelial cells. Changes in the surface contours of uterine epithelial cells from the afternoon of day 6 to the morning of day 9 of pseudopregnancy were similar to those present after attachment in normal pregnancy although somewhat delayed. The presence of short, irregular microvilli was seen from as early as day 7 of pseudopregnancy, with regular microvilli returning to the epithelial surface by days 8-9 of pseudopregnancy but to a slightly lesser extent as compared to normal pregnancy. Furthermore, observations made on the afternoon of day 6 to the morning of day 7 of pseudopregnancy showed that the uterine lumen was closed down and that complete membrane flattening between opposing uterine epithelial cells was seen all along the uterus in the absence of a blastocyst. These observations establish that the "plasma membrane transformation" does not depend on blastocyst implantation.     

Effect of time of day on aerobic contribution to the 30-s Wingate test performance

The purpose of this study was to evaluate the effects of time of day on aerobic contribution during high-intensity exercise. A group of 11 male physical education students performed a Wingate test against a resistance of 0.087 kg . kg(-1) body mass. Two different times of day were chosen, corresponding to the minimum (06:00 h) and the maximum (18:00 h) levels of power. Oxygen uptake (.VO(2)) was recorded breath by breath during the test (30 sec). Blood lactate concentrations were measured at rest, just after the Wingate test, and again 5 min later. Oral temperature was measured before each test and on six separate occasions at 02:00, 06:00, 10:00, 14:00, 18:00, and 22:00 h. A significant circadian rhythm was found in body temperature with a circadian acrophase at 18:16+/-00:25 h as determined by cosinor analysis. Peak power (P(peak)), mean power (P(mean)), total work done, and .VO(2) increased significantly from morning to afternoon during the Wingate Test. As a consequence, aerobic contribution recorded during the test increased from morning to afternoon. However, no difference in blood lactate concentrations was observed from morning to afternoon. Furthermore, power decrease was greater in the morning than afternoon. Altogether, these results indicate that the time-of-day effect on performances during the Wingate test is mainly due to better aerobic participation in energy production during the test in the afternoon than in the morning.     

Changes in plasma progesterone levels during the estrous cycle and pregnancy in 4-day cyclic mice

Changes in plasma progesterone levels during the estrous cycle and pregnancy were determined in group-housed IVCS strain mice showing regular 4-day cycles in the absence of a male. The pattern of progesterone secretion during the estrous cycle consisted of a large peak and a small one, the former during the late afternoon of proestrus and the latter on the afternoon of metestrus. From Day 0 to Day 2 of pregnancy, a sharp rise was observed, and then this level reached a plateau. A marked increase in progesterone was shown from Day 13 until the day before parturition.     

Morphological,molecular and hormonal adaptations to early morning versus afternoon resistance training

It has been clearly established that maximal force and power is lower in the morning compared to noon or afternoon hours. This morning neuromuscular deficit can be diminished by regularly training in the morning hours. However, there is limited and contradictory information upon hypertrophic adaptations to time-of-day-specific resistance training. Moreover, no cellular or molecular mechanisms related to muscle hypertrophy adaptation have been studied with this respect. Therefore, the present study examined effects of the time-of-day-specific resistance training on muscle hypertrophy, phosphorylation of selected proteins, hormonal concentrations and neuromuscular performance. Twenty five previously untrained males were randomly divided into a morning group (n = 11, age 23 ± 2 yrs), afternoon group (n = 7, 24 ± 4 yrs) and control group (n = 7, 24 ± 3 yrs). Both the morning and afternoon group underwent hypertrophy-type of resistance training with 22 training sessions over an 11-week period performed between 07:30–08:30 h and 16:00–17:00 h, respectively. Isometric MVC was tested before and immediately after an acute loading exclusively during their training times before and after the training period. Before acute loadings, resting blood samples were drawn and analysed for plasma testosterone and cortisol. At each testing occasion, muscle biopsies from m. vastus lateralis were obtained before and 60 min after the acute loading. Muscle specimens were analysed for muscle fibre cross-sectional areas (CSA) and for phosphorylated p70S6K, rpS6, p38MAPK, Erk1/2, and eEF2. In addition, the right quadriceps femoris was scanned with MRI before and after the training period. The control group underwent the same testing, except for MRI, between 11:00 h and 13:00 h but did not train. Voluntary muscle strength increased significantly in both the morning and afternoon training group by 16.9% and 15.2 %, respectively. Also muscle hypertrophy occurred by 8.8% and 11.9% (MRI, p < 0.001) and at muscle fibre CSA level by 21% and 18% (p < 0.01) in the morning and afternoon group, respectively. No significant changes were found in controls within these parameters. Both pre- and post-training acute loadings induced a significant (p < 0.001) reduction in muscle strength in all groups, not affected by time of day or training. The post-loading phosphorylation of p70S6Thr421/Ser424 increased independent of the time of day in the pre-training condition, whereas it was significantly increased in the morning group only after the training period (p < 0.05). Phosphorylation of rpS6 and p38MAPK increased acutely both before and after training in a time-of-day independent manner (p < 0.05 at all occasions). Phosphorylation of p70S6Thr389, eEF2 and Erk1/2 did not change at any time point. No statistically significant correlations were found between changes in muscle fibre CSA, MRI and cell signalling data. Resting testosterone was not statistically different among groups at any time point. Resting cortisol declined significantly from pre- to post-training in all three groups (p < 0.05). In conclusion, similar levels of muscle strength and hypertrophy could be achieved regardless of time of the day in previously untrained men. However, at the level of skeletal muscle signalling, the extent of adaptation in some parameters may be time of day dependent.     

Hormonal Interrelationships in Postpartum Suckled Dairy Cows

Three cross-bred cows calved in March and April and were followed until day 62 after parturition. Each animal was suckled by 2 calves ad libitum. All calves were removed from the cows on day 55 after parturition. Blood was collected 3 times per day from the jugular vein by venipuncture. On 4 occasions after parturition - i.e. days 7–8, 21–22, 35–36 and 49–50, the cows were bled through a jugular venous catheter every 30 min during the 24 h. The plasma samples were analyzed for the content of 15-keto-13,14-dihydro-PGF2α (main PGF2α metabolite), LH, prolactin, Cortisol and progesterone by radioimmunoassay methods. The concentration of PGF2α increased from 280 to 730 pmol/1 within the last 4 days before parturition. The highest geometric mean was 3106 pmol/1 on the day of parturition. Thereafter a steady decrease of PGF2α metabolite concentration was seen until day 21 when it reached plateau at 148 pmo/1. In all cows plasma LH concentrations increased significantly (P<0.05) from about 1.6 µg/l on days 7–8 to 2.4 µg/1 on days 21–22 post partum. The frequency of LH pulses showed no tendency to increase as the postpartum period progressed and averaged 6.5 pulses/24 h. Mean plasma LH concentrations increased from 2.1 µg/l 2 days before weaning to 3.2 µg/l 2 days after weaning (P<0.05). LH peaks occurred less frequently in association with prolactin and Cortisol peaks than in their absence. A partial positive correlation between PGF2α metabolite and Cortisol (r = 0.30) was found on days 7–8 post partum. Correlation between prolactin and Cortisol on days 7–8 and 21–22 post partum was also positive (r = 0.20 and r = 0.27, respectively). There was a negative correlation between LH and Cortisol on days 7–8 (r = −0.27) and days 49–50 (r = −0.21) post partum. The first and short progesterone increase observed after weaning was terminated in conjuction with PGF2α metabolite peaks.     

Changes in ovarian blood flow and secretion of progesterone and 20 alpha-hydroxypregn-4-en-3-one on day 16 and the morning and afternoon of day 22 of pregnancy in the rat

During late pregnancy in rats, ovarian secretion of progesterone decreases and that of its reduced metabolite, 20 alpha-hydroxypregn-4-en-3-one (20 alpha-OHP), increases. The present study was undertaken to determine whether changes in ovarian blood flow are consistent with changes in progestin secretion. Rats (n = 5 per group) were examined on Day 16, the time of maximal progesterone secretion, and in the morning (AM) and afternoon (PM) of Day 22, the day prior to parturition. Ovarian blood flow was monitored continuously for 60 to 80 min, and serial samples of arterial and ovarian venous blood were obtained at 20-min intervals for determination of ovarian secretion rates of progesterone and 20 alpha-OHP. Ovarian blood flow increased from 0.38 +/- 0.04 ml/min (mean +/- SEM) on Day 16, to 0.77 +/- 0.05 and 0.78 +/- 0.04 ml/min on Day 22 AM and PM, respectively, whereas the secretion of progesterone decreased from 26.9 +/- 4.0 to 4.5 +/- 1.0 and 3.2 +/- 0.3 micrograms/h per ovary. The secretion of 20 alpha-OHP was similar on Day 16 and Day 22 AM (5.6 +/- 1.7 and 5.4 +/- 1.3 micrograms/h per ovary) but then increased to 18.9 +/- 1.2 micrograms/h per ovary by Day 22 PM. Thus the amount of total progestins secreted per unit rate of blood flow relative to that on Day 16 (100%) fell to 15% and 34% on the morning and afternoon of Day 22, respectively. Clearly, the relative changes in ovarian progestin secretion and blood flow in the rat near term to not conform to patterns observed at luteal regression in some other species.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of Time of Day on Aerobic Contribution to the 30‐s Wingate Test Performance

The purpose of this study was to evaluate the effects of time of day on aerobic contribution during high‐intensity exercise. A group of 11 male physical education students performed a Wingate test against a resistance of 0.087 kg · kg^?1 body mass. Two different times of day were chosen, corresponding to the minimum (06:00 h) and the maximum (18:00 h) levels of power. Oxygen uptake (V˙O₂) was recorded breath by breath during the test (30 sec). Blood lactate concentrations were measured at rest, just after the Wingate test, and again 5 min later. Oral temperature was measured before each test and on six separate occasions at 02:00, 06:00, 10:00, 14:00, 18:00, and 22:00 h. A significant circadian rhythm was found in body temperature with a circadian acrophase at 18:16±00:25 h as determined by cosinor analysis. Peak power (P_peak), mean power (P_mean), total work done, and V˙O₂ increased significantly from morning to afternoon during the Wingate Test. As a consequence, aerobic contribution recorded during the test increased from morning to afternoon. However, no difference in blood lactate concentrations was observed from morning to afternoon. Furthermore, power decrease was greater in the morning than afternoon. Altogether, these results indicate that the time‐of‐day effect on performances during the Wingate test is mainly due to better aerobic participation in energy production during the test in the afternoon than in the morning.     

Psychological stressors as a model of maternal adversity: diurnal modulation of corticosterone responses and changes in maternal behavior

Maternal adversity is associated with long-lasting consequences on cognitive development, behavior and physiological responses in rat offspring. Few studies have examined whether repeated maternal stress produces repeated activation of the hypothalamus-pituitary-adrenal (HPA) axis in mothers and whether it modifies maternal behavior. Here, we tested a novel model of perinatal stress using repeated exposure to "purely" psychological stressors throughout the gestation and lactation periods in rats. We first tested the diurnal influences of repeated 1-h strobe light exposure on maternal corticosterone secretion. Despite the hyporesponsiveness to stress documented in late pregnant and lactating mothers, we observed an enhanced response to strobe light in the afternoon compared to the morning in stressed mothers during lactation. Next, dams were exposed to 24-h forced foraging followed by 10-h wet bedding during the diurnal peak of corticosterone secretion. Although no corticosterone responses to forced foraging and wet bedding were observed, the combination of both stressors had a significant effect on maternal behavior. Mother-pup interactions were significantly altered during the first 8 days of lactation. Taken together, these findings suggest that lactating mothers maintain responsiveness to specific and repeated psychological stressors, in particular at the time of the diurnal peak in corticosterone secretion. Depending on the stressor applied, either neuroendocrine activation or changes in maternal behavior might be important determinants of the long-term consequences in the offspring. The combination of forced foraging, wet bedding and strobe light might represent a novel model of mild maternal adversity using "purely" psychological stressors.