timing systems such as circadian clocks, indicating that delays in ERα, PR, and Pax-2 expression reflect an underlying estrous cycle-responsive timing system in the mammary gland. Evidence is presented that Pax-2 is a molecular component of this timing
Gary B Silberstein, Katharine Van Horn, Eva Hrabeta-Robinson, and Jennifer Compton
J L Crawford, B P Thomson, M F Beaumont, and D C Eckery
fertile although puberty is delayed ( Bole-Feysot et al. 1998 ). Prl is involved in maintenance of the corpus luteum (CL) by stimulating the expression of both oestrogen and luteinising hormone (LH) receptors ( Gibori 1993 ) and by suppressing
C. E. MCCORMACK and RAJAGOPALA SRIDARAN
In order to determine whether the timing of ovulation in rats was controlled by an endogenous circadian rhythm, the hour of ovulation was determined by observing tubal ova during laparotomy in adult rats exposed to full animal room illumination (150 lux) during daily photoperiods of 14 h (full LD), continuous 150 lux illumination (full LL), daily dim (0·2 lux) photoperiods of 14 h (dim LD), continuous 0·2 lux illumination (dim LL) or continuous darkness (DD). Rats in all groups except those exposed to full LL continued normal cyclic ovulation. By the second oestrous cycle, most rats in the full LL group failed to ovulate, even though they showed characteristic cyclic changes in the vaginal smear pattern. The hour at which ovulation occurred was similar in rats exposed to full LD, dim LD or DD but was delayed in rats exposed to full LL or dim LL; the longer the period of exposure, the greater was the delay. For a given length of exposure, ovulation was delayed more in full LL than in dim LL. The full LL used in this study produced persistent vaginal oestrus within 40 days, whereas the dim LL did not. The delayed ovulation in rats exposed to dim LL was associated with a delayed preovulatory surge of LH. These results are consistent with the hypothesis that the timing of the preovulatory surge of LH and ovulation are controlled by an endogenous circadian rhythm, which in most rats has a periodicity in continuous light of slightly longer than 24 h.
R. SRIDARAN and C. E. McCORMACK
Continuous monitoring of wheel-running activity and determination of the time of ovulation in rats by serial laparotomies revealed that ovulation followed the onset of running at prooestrus by approximately 9 h (range 7–11 h). This temporal relationship held in rats in which the period of the circadian rhythm had been modified (entrained) by daily exposure to 14 h photoperiods, and in rats in dim continuous light whose rhythms were non-entrained (freerunning). Knowledge of this temporal relationship between the two rhythms made it possible to give bright light signals at known points in the circadian cycle of the rat and to observe the effects on the timing of running and ovulation in subsequent cycles. Giving daily light signals near the onset of running (i.e. at subjective dusk) delayed, whereas giving signals near the end of running (i.e. at subjective dawn) advanced, the time of running and ovulation in subsequent cycles. These results indicate that in rats exposed to the usual laboratory photoperiod the delaying effect of dusk light and the advancing effect of dawn light balance one another; thus the preovulatory surge of LH occurs at a relatively consistent time at prooestrus.
M. B. TER HAAR and P. C. B. MACKINNON
Ovulation was delayed for 24 h after the administration of sodium pentobarbitone (Nembutal, 35 mg/kg body weight) at 14.00 h, before the critical period on the afternoon of prooestrus. The expected preovulatory surge of serum LH at 18.00 h of pro-oestrus was also delayed until 21.00 h on the following day; however, increased levels (> 12 ng/ml) were observed in 14 out of 23 animals (killed by decapitation) at 21.00 h on the day of Nembutal administration. The serum FSH rise observed on the morning of expected oestrus was extended after Nembutal treatment, and a further rise was noted 24 h later.
Peak levels of incorporation of 35S from methionine into protein of the median eminence area (ME) and of the anterior pituitary (AP) which normally occur about the time of the preovulatory LH surge, were also delayed until 21.00 h on the day following Nembutal administration.
Neither ovulation nor the preovulatory gonadotrophin rises with their accompanying changes in incorporation in the ME and the AP, were altered by Nembutal administered after the pro-oestrous critical period.
Thus Nembutal, while blocking ovulation, inhibits the circadian rhythm of incorporation of 35S from methionine in the brain as well as the peaks of incorporation in the median eminence and the anterior pituitary which accompany the normal preovulatory surges of gonadotrophin.
J Lund, J Arendt, SM Hampton, J English, and LM Morgan
The circadian rhythms of many night-shift workers are maladapted to their imposed behavioural schedule, and this factor may be implicated in the increased occurrence of cardiovascular disease (CVD) reported in shift workers. One way in which CVD risk could be mediated is through inappropriate hormonal and metabolic responses to meals. This study investigated the responses to standard meals at different circadian times in a group of night-shift workers on a British Antarctic Survey station at Halley Bay (75 degrees S) in Antarctica. Twelve healthy subjects (ten men and two women) were recruited. Their postprandial hormone and metabolic responses to an identical mixed test meal of 3330 kJ were measured on three occasions: (i) during daytime on a normal working day, (ii) during night-time at the beginning of a period of night-shift work, and (iii) during the daytime on return from night working to daytime working. Venous blood was taken for 9 h after the meal for the measurement of glucose, insulin, triacylglycerol (TAG) and non-esterified fatty acids. Urine was collected 4-hourly (longer during sleep) on each test day for assessment of the circadian phase via 6-sulphatoxymelatonin (aMT6s) assay. During normal daytime working, aMT6s acrophase was delayed (7.7+/-1.0 h (s.e.m.)) compared with that previously found in temperate zones in a comparable age-group. During the night shift a further delay was evident (11.8+/-1.9 h) and subjects' acrophases remained delayed 2 days after return to daytime working (12.4+/-1.8 h). Integrated postprandial glucose, insulin and TAG responses were significantly elevated during the night shift compared with normal daytime working. Two days after their return to daytime working, subjects' postprandial glucose and insulin responses had returned to pre-shift levels; however, integrated TAG levels remained significantly elevated. These results are very similar to those previously found in simulated night-shift conditions; it is the first time such changes have been reported in real shift workers in field conditions. They provide evidence that the abnormal metabolic responses to meals taken at night during unadapted night shifts are due, at least in part, to a relative insulin resistance, which could contribute to the documented cardiovascular morbidity associated with shift work. When applied to the 20% of the UK workforce currently employed on shift work, these findings have major significance from an occupational health perspective.
N. D. Martensz, S. V. Vellucci, L. M. Fuller, B. J. Everitt, E. B. Keverne, and J. Herbert
Circadian rhythms in cortisol and testosterone in both blood and cerebrospinal fluid (CSF) were studied in four groups of male and female talapoin monkeys. Samples were taken 4 h apart under two conditions: whilst the sexes were kept separate (isosexual) and again after 24 h of interaction (heterosexual). There were similar rhythms in cortisol in males and females during the isosexual condition, though in blood (but not in CSF) mean levels were higher in females. Heterosexual interaction increased cortisol levels in both sexes (though more so in males), and also altered the shape of the rhythm, acrophase being delayed by 4 h in males and by 2 h in females. The amplitude of the rhythm was not altered. Cortisol levels were positively correlated in both males and females with the amount of aggression received from other males, but not from females nor with the animals' social rank.
Circadian rhythms in serum testosterone in males were also altered by heterosexual interaction. Access to females delayed acrophase by 2 h, but had no effect on mean levels (unlike the effect on cortisol). As for cortisol, the amplitude of the testosterone rhythm remained unchanged. Serum testosterone was negatively correlated with aggression from males, but not from females nor with sexual interaction. This was associated with a pronounced decrease in the levels of testosterone during the night, not observed in males receiving no aggression from others. There was a non-significant trend towards a positive correlation between social rank and serum testosterone.
These results show that social behaviour in groupliving primates has major effects on the parameters of the circadian pattern of secretion of both cortisol and testosterone. Aggression received from males seems to be a potent factor associated with the daily rhythms in both hormones, though there may be rank-related effects in the case of testosterone.
J. Endocr. (1987) 115, 107–120
Michael Hastings, John S O’Neill, and Elizabeth S Maywood
new cycle of circadian gene expression is delayed by elevated Cry. Entrainment of the SCN by light Tau mutant hamsters, Clock mutant, hPer2 mutant and Fbxl3 mutant mice show atypical patterns of synchronisation to 12 h
R. Valcavi, C. Dieguez, C. Azzarito, C. Artioli, I. Portioli, and M. F. Scanlon
We have tested the hypothesis that α-adrenergic drive is involved in the nocturnal increase in TSH in man. Seven mildly hypothyroid women (basal TSH levels 5·0–11·0 mU/1), aged 38–60 years, and nine euthyroid women, aged 27–60 years, were studied. Subjects underwent α-adrenergic blockade by infusion of thymoxamine (210 μg/min from 19.00 to 24.00 h); the same women were used as controls, with saline infused on different nights. Subjects were not allowed to sleep during the study period.
A clear evening rise in basal TSH levels was apparent in both normal subjects and patients. Although overall secretion of TSH was slightly decreased in normal subjects (mean ± s.e.m. area under the curve, 29·93 ± 0·96 vs 30·71 ±mU/1 per h; P<0·05), thymoxamine infusion did not produce any major alteration in the gradual rise in TSH levels during the evening (incremental change above baseline +0·96± 0·21 during control infusion and + 0·97 ± 0·27 mU/1 during thymoxamine infusion). In mildly hypothyroid patients the TSH changes were exaggerated and α-adrenergic blockade caused a reduction in basal TSH levels and a delayed rise in TSH (incremental change above baseline +2·93 ± 1·42 during control infusion and +2·26 ± 0·73 mU/1 during thymoxamine infusion; P < 0·02). Overall TSH secretion was significantly decreased by thymoxamine (mean ± s.e.m. area 106 ± 2·45 mU/1 per h vs 123·32 ± 3·68 in the control study; P<0·0001). As expected, no circadian change was observed in basal prolactin levels in either controls or patients.
Although α-adrenergic pathways may play a role in modulating the nocturnal increase in basal TSH levels, our data suggest that the evening rise in TSH is not a consequence of a primary increase in α-adrenergic drive. The increased TSH changes of mildly hypothyroid patients may, however, be sustained by increased central α-adrenergic stimulation of the TSH secretion.
J. Endocr. (1987) 115, 187–191
Elizabeth K Fletcher, Monica Kanki, James Morgan, David W Ray, Lea M Delbridge, Peter J Fuller, Colin D Clyne, and Morag J Young
.1016/0092-8674(83)90430-0 ) 10.1016/0092-8674(83)90430-0 Cheon S Park N Cho S Kim K 2013 Glucocorticoid-mediated Period2 induction delays the phase of circadian rhythm . Nucleic Acids Research 41 6161 – 6174 . ( https://doi.org/10.1093/nar/gkt307 ) 10.1093/nar/gkt307