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ABSTRACT
Circadian and ultradian rhythms in urinary excretion of 17-hydroxycorticosteroids were documented individually during an 8-day span in two pairs of young male twins. Studies were performed once at the age of 6 years for dizygotic twins and twice at the ages of 4·3 and 10·3 years for monozygotic twins. Four different methods were used for time-series analyses: chronograms (raw data), best-fitting curves resulting from cosinor analyses, power spectra and correlations of time-qualified data. Estimates of rhythm parameters (prominent periods, acrophases, etc.) as well as shapes of curves were closer in mono- than in dizygotic twins. Both similarities and small differences in rhythm characteristics of monozygotic twins were detected at both ages considered.
J. Endocr. (1985) 105, 247–253
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Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, College of Engineering, Wellcome Trust Centre for Biomedical Modelling and Analysis, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, UK
Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, College of Engineering, Wellcome Trust Centre for Biomedical Modelling and Analysis, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, UK
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Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, College of Engineering, Wellcome Trust Centre for Biomedical Modelling and Analysis, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, UK
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glucocorticoid ultradian rhythm. (a) Stress and circadian inputs activate the hypothalamic PVN to release CRH and AVP into the hypothalamic–pituitary portal circulation. CRH and AVP activate corticotroph cells in the anterior pituitary, which respond with the
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Abstract
Fetal maturation and the timing of parturition in both sheep and primates are thought to be controlled by the hypothalamic-pituitary-adrenal axis but little is known about the endocrinology of the equine fetus. We investigated the ontogeny of plasma concentrations of adrenocorticotropic hormone (ACTH), cortisol and corticosteroid binding capacity in the late-gestation fetal horse. We also wished to determine whether there is ultradian rhythmic release of ACTH and cortisol in fetal horses and we compared fetuses to maternal and non-pregnant adult horses. Six fetuses, 278–304 days gestation (term ≈335), were catheterized and sampled daily until delivery. Mean (± s.e.m.) ACTH concentrations increased significantly from 159 ±21 to 246 ±42 pg/ml over the last 2 days before parturition. Fetal cortisol increased significantly from 3·1±1·0 to 13·4±3·7 ng/ml (mean±s.e.m.) over the last 9 days before delivery. The slope of regressions for ACTH and cortisol concentrations with respect to time were positive in all subjects and statistically significant in 3 of 6 for ACTH and 5 of 6 for cortisol. Fetal corticosteroid binding capacity declined from 49·5 ±20·5 to 16·1 ± 2·2 ng/ml (mean ± s.e.m.) over the last 10 days before parturition. However, the greatest changes in ACTH, cortisol and corticosteroid binding capacity occurred very late in gestation, during the last 48 to 72 h before parturition. Significant peaks and nadirs in plasma ACTH concentration were detected in all 20 experiments and in plasma cortisol concentration in 17 of 20 experiments using Cluster analysis. We found statistically significant periods of oscillation between 11 and 64 min in plasma ACTH (19 of 20 experiments) and cortisol (15 of 20 experiments) using power spectral density analysis. Statistically significant periods between 11 and 17 min were detected in 11 of 20 experiments for ACTH and in 8 of 20 for cortisol. We conclude that: 1) at the end of gestation, equine fetal plasma ACTH and cortisol concentrations increase while corticosteroid binding capacity decreases suggesting that there is a disproportionately large increase in unbound cortisol at this time; 2) the secretion of ACTH and cortisol is rhythmic in both fetal and adult horses; 3) most animals exhibit a period of oscillation between 11 and 17 min; and 4) there is no apparent developmental change from late gestation to adulthood in the ultradian oscillator influencing ACTH and cortisol secretion in this species.
Journal of Endocrinology (1995) 144, 271–283
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Three Merino ewes, adapted for about 3 weeks to their environment, were bled at 10 min intervals through a jugular venous cannula. Radioimmunoassay of plasma samples for cortisol revealed marked diurnal variations with peak levels just after midnight and lowest values in the afternoon. This rhythm appeared to result from a changing amplitude associated with a distinct ultradian rhythm (frequency 0·8–1·2 cycles/h) in the plasma level of cortisol. Calculation of the daily rate of secretion of cortisol from the hormone profiles gave a mean value of 8·49 mg. Arguments are put forward in favour of this method for obtaining the true rate of secretion of cortisol.
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SUMMARY
Adrenocorticotrophin (ACTH) and corticosterone in the plasma of adult female rats were measured sequentially at 4 h intervals for 24 h before and after lesions of the suprachiasmatic nuclei or treatment with p-chlorophenylalanine (to inhibit serotonin synthesis). After lesions or p-chlorophenylalanine treatment, the concentrations of ACTH were diminished relative to those in control animals and rhythmic changes could not be detected. However, injection of animals, pretreated with p-chlorophenylalanine, with 5-hydroxytryptophan (60 mg/kg) 8 h before the time when plasma ACTH is maximal in intact animals, stimulated ACTH secretion up to control values. Mean corticosterone concentrations in plasma remained unchanged (after lesions) or increased (after p-chlorophenylalanine). This increase was associated with an increased minimal concentration of corticosterone. After both treatments there was evidence of continued circadian or ultradian rhythms of corticosterone concentration.
Locomotor activity of female rats given identical treatment, but without blood sampling, indicated that nocturnal activity was diminished after lesions whereas diurnal activity was enhanced after p-chlorophenylalanine treatment. Periodicity analysis detected the persistence of free-running circadian, and sometimes ultradian activity, rhythms. Adrenalectomy did not alter further the activity pattern observed in rats with lesions.
These results therefore support the proposition that both the suprachiasmatic nuclei and the serotoninergic system play an irreplaceable role in the mechanism of ACTH secretory rhythms. The suprachiasmatic nuclei are also important for synchronization of locomotor activity and corticosterone rhythms, which may both persist after the suppression of ACTH rhythms.
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Secretory profiles of prolactin and growth hormone (rGH) over a period of 6 h were obtained from unrestrained pinealectomized or sham-operated control male rats, both groups having been chronically implanted with right atrial cannulae and acclimatized to isolation in special blood sampling cages with a strict cycle of 12 h light: 12 h darkness (L: D). Hormone profiles were obtained from 2 h before to 4 h after the commencement of the light period.
In intact animals, secretion of prolactin was episodic without a clear ultradian rhythm except that secretory bursts tended to be larger during the dark period. Furthermore, a peak of prolactin occurred regularly at the commencement of the light period, even though subsequent peaks were diminished in amplitude. Mean concentrations of prolactin during the dark period were significantly higher than later daytime values, supporting the view that there is a diurnal prolactin rhythm. Pinealectomy altered the secretory patterns in prolactin so that peaks became more prominent early in the light period but mean concentrations of prolactin eventually fell as they did in control animals and there was no difference in concentrations of prolactin over a period of 6 h between the two groups. Pinealectomy, therefore, slightly delayed the fall in mean prolactin concentrations which normally occurs in the light period.
Secretion of rGH was rhythmic with interpeak intervals and mean concentrations in which there were no differences between control and pinealectomized groups. Inhibition of secretory episodes of rGH by the interface between darkness and light was impaired in pinealectomized animals with a delay in the appearance of the first diurnal trough.
It was concluded that pinealectomy attenuates L: D cycle regulation of secretory rhythms of prolactin and rGH to a minor degree.
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ABSTRACT
The ability of continuously delivered GH-releasing factor (GRF) to enhance GH secretion while maintaining the normal ultradian GH rhythm was investigated. Synthetic human GH-releasing factor (hGRF(1–44)NH2) was continuously infused for 4 days by means of i.v. catheters to 11-week-old broiler chickens. At this age, overall endogenous GH secretion is low, and baseline GH is barely detectable. Six birds per treatment received vehicle (control), 0·324 mg hGRF(1–44)NH2/kg body weight per day (low dose) or 3·24 mg hGRF(1–44)NH2/kg body weight per day (high dose). After 4 days of GRF conditioning, concurrent with continued GRF infusion, serial blood samples were removed via atrial catheters at 15-min intervals for 6 h and GH plasma profiles determined.
High dose GRF significantly increased GH plasma concentrations over tenfold compared with controls; however, most of this increase reflected an increase in basal GH, which was reinstated to juvenile baseline levels. Augmentation of pulse amplitude above this increased baseline was not proportionately as high, and failed to reach juvenile levels. The ultradian rhythm of GH was not altered by continuous GRF administration.
Both low and high dose GRF treatments resulted in significant enlargement of the anterior pituitary gland. Total pituitary GH mRNA levels, although elevated over twofold by GRF treatment, were not significantly different from controls. Measures of plasma GH magnitude (overall and baseline mean, and peak amplitude) were significantly correlated with pituitary GH mRNA for control birds, but were not correlated for GRF treatments.
Feed intake was markedly depressed (33%) on the high dose GRF treatment, in conjunction with total inhibition of body weight gain over the 4-day period of administration. Longitudinal bone growth and width of the epiphyseal growth plate were also significantly reduced by high dose GRF treatment, probably reflecting the reduced level of nutrient intake, despite high circulating concentrations of GH.
Journal of Endocrinology (1992) 135, 371–382
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Seasonal changes in the activity and responsiveness of the adrenal gland in red deer (Cervus elaphus) stags were quantified by measuring 24 h endogenous cortisol secretory profiles and plasma cortisol responses to either administration of exogenous ACTH or a standardised stressor during November (period of velvet growth), February (pre-rut), April (mid-rut) and July (post-rut) (southern hemisphere) using a remote blood sampling device (DracPac). Ultradian rhythms in the concentration of plasma cortisol were observed resulting from the episodic secretion of cortisol from the adrenal cortex at a mean rate of 0.8 pulses/h. Circadian rhythms in plasma cortisol concentrations were also found in 11 out of the 20 complete 24 h profiles (mean amplitude, 3.8+/-1.4 ng/ml). Seasonal rhythms in mean 24 h plasma cortisol concentrations and cortisol pulse parameters were also observed. Mean 24 h plasma cortisol concentrations were higher in November (12.5+/-1.0 ng/ml) than in February (6.3+/-1.0 ng/ml), April (4.0+/-1.0 ng/ml) or July (4.2+/-1. 0 ng/ml). Cortisol pulse height, nadir and amplitude were all significantly higher in November than at other times of the year (P<0.01). Peak cortisol concentrations following infusion of ACTH(1-24) (0.04 IU kg(-1)) were higher (P<0.05) in November (55.8+/-2.7 ng/ml) and lower (P<0.001) in April (33.7+/-1.8 ng/ml) than those in February and July (48.7+/-2.0 ng/ml and 45.4+/-2.0 ng/ml respectively). The area under the cortisol response curve was significantly smaller (P<0.05) in April (266.6+/-15.3 ng/ml/190 min) than at other times of the year (February, 366.1+/-15.3 ng/ml/190 min; July, 340.7+/-15.3 ng/ml/190 min and November, 387.8+/-21.2 ng/ml/190 min). These data demonstrate that the adrenal gland of the red deer stag exhibits ultradian, circadian and seasonal rhythms in activity, and that its responsiveness to ACTH varies with season. November, a period of reproductive quiescence in the southern hemisphere, with new antler growth and rapid weight gain, is associated with higher mean plasma cortisol concentrations and a greater responsiveness to exogenous ACTH. In contrast, the breeding season is associated with lower adrenal activity and responsiveness.
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ultradian rhythms in the HPA axis. There is also evidence that the mechanistic link between ACTH and glucocorticoid secretion might indeed be less tight than previously thought: under various physiological and pathophysiological conditions, the pulses of
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Department of Biophysics and Life Sciences, Bioinformatics Project of Japan Science and Technology Agency, Laboratory of Exercise Biochemistry and Neuroendocrinology, Department of Urology, Graduate School of Arts and Sciences, University of Tokyo, 3‐8‐1 Komaba, Meguro‐ku, Tokyo 152-8902, Japan
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Department of Biophysics and Life Sciences, Bioinformatics Project of Japan Science and Technology Agency, Laboratory of Exercise Biochemistry and Neuroendocrinology, Department of Urology, Graduate School of Arts and Sciences, University of Tokyo, 3‐8‐1 Komaba, Meguro‐ku, Tokyo 152-8902, Japan
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Department of Biophysics and Life Sciences, Bioinformatics Project of Japan Science and Technology Agency, Laboratory of Exercise Biochemistry and Neuroendocrinology, Department of Urology, Graduate School of Arts and Sciences, University of Tokyo, 3‐8‐1 Komaba, Meguro‐ku, Tokyo 152-8902, Japan
Department of Biophysics and Life Sciences, Bioinformatics Project of Japan Science and Technology Agency, Laboratory of Exercise Biochemistry and Neuroendocrinology, Department of Urology, Graduate School of Arts and Sciences, University of Tokyo, 3‐8‐1 Komaba, Meguro‐ku, Tokyo 152-8902, Japan
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ultradian rhythm but a delayed response to forced swim stress . Endocrinology 149 3244 – 3253 . ( doi:10.1210/en.2008-0103 ) Eckel-Mahan KL Storm DR 2009 Circadian rhythms and memory: not so simple as cogs and gears . EMBO Reports 10 584
