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J. D. FEW
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K. J. COLLINS
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The steroid 11-oxygenation index (i.e. the ratio of the urinary metabolites of cortisol precursors to those of cortisol) has been used by Hill (1960) and by Edwards, Makin & Barratt (1964) in the diagnosis of congenital adrenal hyperplasia. Both showed that any circadian variations in the index were small compared with the gross abnormalities encountered in this condition. In the course of physiological studies on temperature and renal excretory circadian rhythms we have observed a small but definite circadian variation in the steroid 11-oxygenation index in normal men.

Six male subjects (ages ranging from 21 to 55 yr.) followed a routine consisting of rest, light activity, feeding and drinking, which was repeated every 90 min. during a 27 hr. experiment. Urine was collected for 3 hr. periods and the 11-deoxy and 11-oxy 17-hydroxycorticosteroids (11-deoxy and 11-oxy 17-OHCS) were separately estimated (Few, 1968) in each sample. The steroid 11-oxygenation index was

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Yvan Touitou
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Alain Carayon
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Alain Reinberg
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André Bogdan
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Hervé Beck
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Effects of age, sex and mental condition on the circadian and circannual rhythmicity of plasma prolactin in human subjects were investigated. Circannual changes were recorded on a circadian basis in January, March, June and October in four groups of subjects: seven young men, six elderly men, six elderly women and six senile demented patients (two men and four women). Blood samples were drawn every 4 h over a 24-h period at the four sampling sessions. Circadian rhythms of the hormone were validated in all groups and at all sampling sessions except twice in elderly demented subjects. The 24-h mean levels of prolactin in plasma were approximately the same in young and elderly subjects. The circadian acrophases were most often located in the vicinity of 02.00–04.00 h. The circannual rhythmicity of the hormone showed a sex difference; the rhythm was not validated in either young or elderly men but was detected in the groups of elderly women and elderly demented patients (mainly women). The acrophases were located in May. This paper strongly suggests a sex difference in the circannual rhythmicity of plasma prolactin levels in elderly subjects.

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LINDA A. LUCAS
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B. E. ELEFTHERIOU
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Diurnal variations in testosterone in plasma were studied in two inbred strains of mice, BALB/cBy and C57BL/6By. Blood was taken every 4 h over 24 h from male mice at 70 days of age using a lighting regimen of 12 h light to 12 h darkness (lights on 07.00–19.00 h). Values of testosterone in plasma were transformed to log(testosterone in ng/ml) to reduce inequality of variance between groups. In both strains, the distribution of pooled values over all times of day was bimodal, and bimodality was present at most times of day. Circadian variation was evaluated by dividing the transformed values into high and low modes at each time of day and testing for significant variation in the number of animals in each mode over time using the chi-squared test. Significant circadian variation was found in the BALB/cBy strain of mice but not in the C57BL/6By strain. The highest number of high mode cases for BALB/cBy mice was at 22.00 h and the lowest number of high mode cases was at 10.00 h. The log transformation and bimodality of these values are presented as biological expressions of blood levels of testosterone and of tissue responses to these levels in the male mouse. The strain difference in circadian variation may be related to reported circadian changes in behaviour and to possible genetic effects on sensitivity to environmental change or capacity to express circadian rhythms.

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M. H. Hastings
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A. P. Walker
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J. Herbert
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ABSTRACT

This study investigated the relationship of two overt circadian rhythms, locomotor activity and melatonin synthesis in the pineal gland, by comparing their responses to asymmetrical reductions in photoperiod. Transfer of male Syrian hamsters from long to short daylengths led to an increase in the duration of both locomotor activity and the period of melatonin synthesis. Over the course of re-entrainment, the two rhythms were held in a stable phase relationship, and the direction of the switch did not influence the rate of decompression or the final phase relationships established after 8 weeks in short daylengths. Decompression of the activity rhythm was not influenced by pinealectomy. Exposure to short photoperiods caused gonadal regression and a consequent decline in serum testosterone levels from 10 to <1 nmol/l. The direction of the photoperiodic switch did not affect the time-course of gonadal regression. These data demonstrate the important influence of photoperiod upon the duration of the nocturnal peak of melatonin production by the pineal and also demonstrate that this effect is one example of a more widespread response of the circadian system. A qualitatively similar signal controls both locomotor activity and melatonin synthesis, although the neural basis of this common mechanism is unclear.

J. Endocr. (1987) 114, 221–229

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A. L. THOMAS
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MARGARET ABEL
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P. W. NATHANIELSZ
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It is now well established that several hormones are secreted in an episodic or pulsatile fashion (McNatty, Cashmore & Young, 1972; Murray & Corker, 1973). When plasma concentrations of certain hormones are examined, peaks occur at intervals related to different features of the 24-h cycle, circadian rhythms (Retiene, Zimmerman, Schindler, Neuenschwander & Lipscomb, 1968). Circadian and episodic patterns in thyroid function have been claimed by certain workers (Bakke & Lawrence, 1965; Blum, Greenspan & Magnum, 1968) and refuted by others (Schatz & Volpe, 1959; Odell, Wilber & Utiger, 1967). A partial explanation of these conflicting results probably lies in functional differences in the level of the hypothalamo-pituitary-thyroidal-peripheral target tissue axis under investigation by different techniques.

Five Jersey bull calves aged between 2 and 80 days were investigated on a total of nine occasions. Five experiments were conducted under natural lighting conditions (daylight from 04.30 to 19.30 h). Calves in the

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J. J. GAGLIARDINO
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MARÍA TERESA PESSACQ
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R. E. HERNÁNDEZ
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O. R. REBOLLEDO
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CENEXA—Centro de Endocrinología Experimentaly Aplicada, CONICET—Universidad Nacional de La Plata, Facultad de Ciencias Médicas, Calle 60 y 120, 1900 La Plata, Argentina

(Received 10 March 1978)

Circadian variations in the serum concentration of immunoreactive insulin in the mouse (Gagliardino & Hernández, 1971) and the effect of fasting and feeding on this rhythm (Pessacq, Rebolledo, Mercer & Gagliardino, 1976) have already been described. However, no information is available on circadian variations in the level of glucagon in the blood of experimental animals and the present experiments were performed to investigate changes in the concentrations of glucagon in the plasma and glycogen and cyclic AMP in the liver of the female mouse over a 24 h period.

Female mice (C3HS strain), 19–21 weeks old, were kept at a constant temperature (25 ± 1·0 °C) under a schedule of 12 h light : 12 h darkness (lights on 06.00–18.00 h) and allowed free

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J. A. M. MATTHEIJ
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J. J. M. SWARTS
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The occurrence of circadian variations in the concentration of prolactin in the plasma of 6- to 9-month-old male rats has been assessed in animals exposed to light for 14 h/day (lights on 06.00–20.00 h). Blood samples were obtained after decapitation, or from individual rats at regular intervals via a permanent cannula. Care was taken to limit stress during sampling. The concentration of prolactin in the plasma was significantly lower between 07.00 and 15.00 h than at other times. Between 15.00 and 20.00 h (during the light period), the concentration of prolactin was significantly higher in comparison with the preceding period, or with the remainder of the 24 h period. During the night, the concentration fluctuated, probably because of episodic releases of the hormone. The possible physiological significance of a circadian rhythm in the plasma concentration of prolactin and the implications for endocrine experimentation are discussed briefly.

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M. D. ROLLAG
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P. L. O'CALLAGHAN
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G. D. NISWENDER
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Department of Physiology and Biophysics, Colorado State University, Fort Collins, Colorado 80523, U.S.A.

(Received 13 September 1977)

Mammalian pineal gland activity is controlled by environmental lighting schedules. Light exerts its influence via a neuronal pathway originating in the retina (Moore & Klein, 1974) and as a consequence of this photoperiodic control, the concentration of melatonin in the plasma is raised during periods of darkness and depressed during periods of light (Rollag & Niswender, 1976). The response of the pineal gland to photostimulation is surprisingly rapid. Within 5 min of a darkness to light transition, there is a precipitous decline in pineal N-acetyltransferase activity in the rat (Deguchi & Axelrod, 1972; Klein & Weller, 1972). In sheep, peripheral concentrations of melatonin decline within 5–10 min of a darkness to light transition (Rollag, O'Callaghan & Niswender, 1978). A circadian rhythm of blood flow to the pineal gland analogous to the rhythm of melatonin

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I. C. McMillen
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G. D. Thorburn
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D. W. Walker
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ABSTRACT

We have measured fetal and maternal plasma concentrations of cortisol, prolactin, GH and glucose in samples collected during a 24-h period in 14 animals between 127 and 142 days of gestation. There was a significant increase in both the mean daily plasma cortisol concentration and mean daily coefficient of variation (C.V.) of plasma cortisol concentrations after 135 days of gestation. There was also a significant variation in the fetal plasma cortisol concentrations with a peak occurring at 19.00 h. There was a significant sinusoidal diurnal rhythm in the plasma prolactin concentrations in both the fetal sheep and pregnant ewe and the maximal prolactin concentrations occurred between 19.00 and 23.00 h (fetal) and 21.00 and 01.00 h (maternal). Although no significant diurnal variation was detected in fetal plasma GH concentrations, there was a significant sinusoidal diurnal rhythm in the plasma GH concentrations of the pregnant ewe and the maximal maternal GH concentrations occurred between 21.00 and 01.00 h. Both the fetal and maternal plasma glucose concentrations showed a significant sinusoidal diurnal rhythm. The maximal maternal and fetal glucose concentrations were measured between 21.00 and 01.00 h and between 23.00 and 03.00 h respectively. We have therefore established that diurnal variations in plasma cortisol and prolactin concentrations exist prenatally. Whether the presence of such hormonal rhythms reflects the activity of an endogenous fetal circadian pacemaker remains to be established.

J. Endocr. (1987) 114, 65–72

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Yvan Touitou
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José Sulon
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André Bogdan
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Catherine Touitou
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Alain Reinberg
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Hervé Beck
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Jean-Claude Sodoyez
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Emilie Demey-Ponsart
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Henri Van Cauwenberge
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Circadian changes in plasma 18-hydroxy-11-deoxycorticosterone (18-OH-DOC), total and unbound cortisol were studied in four groups: seven healthy young men, six elderly men, six elderly women and six elderly demented patients of both sexes. The daily activities of the subjects were synchronous; blood samples were taken every 4 h and 4 hourly urine samples were collected only from the young men. A circadian rhythm was defined for plasma 18-OH-DOC, total and unbound cortisol in all groups; the secretory patterns of these steroids were parallel, as were the profiles of urinary 18-OH-DOC and unconjugated cortisol. When compared with respect to sex, the 24-h mean level of total cortisol was higher in women; that of unbound cortisol was higher in the three groups of elderly patients than in the young men. No major changes in plasma steroids were observed between elderly demented patients (mainly women) and healthy elderly women. The phasing of total and unbound cortisol showed no major modifications with age, sex or senile dementia. Acrophases of 18-OH-DOC were earlier in elderly patients than in young men. Amplitudes were not modified with sex in elderly patients but were always lower in the demented patients. A circadian rhythm was defined for 18-OH-DOC, unconjugated cortisol, 17-hydroxycorticosteroids (17-OH-CS) and 17-ketosteroids in the urine of the young men. The acrophases of 18-OH-DOC and unbound cortisol were close, as were those of 17-OH-CS and 17-ketosteroids. The lag was short between the acrophases of 18-OH-DOC in plasma and urine and between those of plasma unbound cortisol and urinary unconjugated cortisol; it was much larger between the acrophases of plasma total cortisol and 17-OH-CS.

Thus, the process of ageing, and the possible alterations in the central nervous system which are often seen in normal ageing, induced no major modifications in the temporal organization of adrenocortical function, even in subjects who were very advanced in age.

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