Gender Difference in Timing of Nocturnal Rise of Subjective Sleepiness

Experimental research of diurnal variations in body temperature and melatonin secretion consistently revealed an earlier entrained circadian phase in women than in men. Since it is well documented that daily fluctuations in self-reported level of sleepiness closely follow the circadian rhythms of melatonin and body temperature, one can predict that gender differences in phase characteristics of the 24-hour fluctuations of subjective sleepiness resemble the differences revealed by research of physiological and hormonal rhythms. Analysis of sleepiness self-scored by 46 male and 54 female participants of sleep deprivation experiments showed that female participants scored significantly higher their midnight sleepiness level. The model-based simulations of sleepiness curves confirmed the prediction of a relatively earlier phase of 24-hour oscillations of sleepiness in women. Such gender differences persisted after accounting for individual variation in habitual sleep times and morning-evening preference. In today’s environment, the earlier circadian phase in women can cause a larger delaying phase shift in response to midnight exposure to artificial light, but, on the other hand, the earlier rise of subjective sleepiness can make them less vulnerable to the delaying shifts.

Aging-related sex-dependent loss of the circulating leptin 24-h rhythm in the rhesus monkey

The adipocyte-derived hormone leptin plays a pivotal role in the regulation of body weight and energy homeostasis. Many studies have indicated that the circulating levels of leptin show a 24-h rhythm, but the exact cause and nature of this rhythm is still unclear. In the present study, we remotely collected blood samples every hour from young and old, male and female rhesus monkeys, and examined their 24-h plasma leptin profiles. In both the young males (10–11 years) and females (7–13 years), a clear 24-h plasma leptin rhythm was evident with a peak occurring ~4 h into the night and a nadir occurring ~1 h into the day (lights on from 0700 to 1900 h). A 24-h plasma leptin rhythm was also observed in the old males (23–30 years), even when they were maintained under constant lighting conditions (continuous dim illumination of ~100 lx). In marked contrast, plasma leptin concentrations were relatively constant across the day and night in old peri- and post-menopausal females (17–24 years), regardless of the lighting schedule. These data establish that rhesus monkeys, like humans, show a daily nocturnal rise in plasma leptin, and the magnitude of this rhythm undergoes a sex-specific aging-dependent attenuation. Furthermore, they suggest that the underlying endocrine mechanism may be driven in part by a circadian clock mechanism.

Lactation modulates diurnal expression profiles of specific leptin receptor isoforms in the rat hypothalamus

We investigated the effects of lactation on diurnal changes in serum leptin and hypothalamic expression of the leptin receptor isoforms, Ob-Ra, -Rb, -Rc, -Re and -Rf in rats. In non-lactating rats, serum leptin concentration was increased at night while hypothalamic mRNA levels of Ob-Rb, -Rc and -Re decreased; by contrast, expression of Ob-Ra and Ob-Rf was unchanged at night. There were significant negative correlations between serum leptin and mRNA expression of Ob-Rb (P<0.001) and Ob-Re (P<0.05), which were independent of time of day. In lactating rats, the nocturnal rise in serum leptin was attenuated. Daytime hypothalamic Ob-Rb mRNA levels were significantly lower than in non-lactating controls, and the normal nocturnal decreases in expression of Ob-Rb, -Rc and -Re were lost. The relationship between serum leptin and Ob-Re expression was not changed by lactation. Lactation had no effect on the expression of Ob-Ra mRNA in the hypothalamus. Decreased daytime Ob-Rb expression could lead to reduced hypothalamic sensitivity to leptin, and thus contribute to increased daytime appetite in lactating rats. Moreover, maintaining high levels of Ob-Re expression could, by increasing hypothalamic leptin-binding protein concentration and reducing local leptin bioavailability, further accentuate hyperphagia. Thus, selective changes in expression of specific isoforms of the leptin receptor may contribute to the hyperphagia of lactation in rats.

Regulation of serum leptin and its role in the hyperphagia of lactation in the rat

The factors regulating serum leptin concentration and its relationship to the hyperphagia of lactation have been investigated in rats. Lactation results in hypoleptinaemia and loss, or at least marked attenuation, of the nocturnal rise in serum leptin. Litter removal resulted in a fall in food intake and restoration of the nocturnal rise in serum leptin. Returning the litter to the mother after a 48-h absence increased food intake and began to reinitiate milk production, but the nocturnal serum leptin levels were still increased at 48 h after litter restoration. Adjusting litter size to four, eight, ten or fourteen pups at parturition resulted in different rates of litter growth and food intake during the subsequent lactation, but had no effect on the degree of hypoleptinaemia. Reducing litter size from ten to four pups at mid-lactation resulted in a transient increase in both serum leptin and pup growth rate, while food intake fell to a level found in rats suckling four pups throughout lactation. Reducing milk production by injection of bromocriptine increased serum leptin, but did not restore the nocturnal rise in serum leptin; food intake decreased, but remained much higher than in non-lactating rats. Feeding a varied, high-energy diet resulted in a decrease in the weight of food ingested, but no change in calorie intake, and had no effect on the hypoleptinaemia. These studies suggested that the hypoleptinaemia of lactating rats is due to negative energy balance, but the loss of the nocturnal rise in serum leptin is due to the suckling stimulus. The negative energy balance of lactation does not appear to be caused by a physical constraint on food intake. While the hypoleptinaemia should facilitate the hyperphagia of lactation, other orexigenic signals must also be involved.

Hypothalamic-pituitary-adrenal axis in the night eating syndrome

The typical neuroendocrine characteristics of the night eating syndrome have previously been described as changes in the circadian rhythm by an attenuation in the nocturnal rise of the plasma concentrations of melatonin and leptin and an increased circadian secretion of cortisol. The aim of this study was to test the hypothesis that night eaters have an overexpressed hypothalamic-pituitary-adrenal axis with an attenuated response to stress. Five female subjects with the night-eating syndrome and five sex-, age-, and weight-matched controls performed a 120-min corticotropin-releasing hormone (CRH) test (100 μg iv). Blood samples were drawn intravenously for measurements of the plasma concentrations of ACTH and cortisol. The results showed that, in night eaters compared with controls, the CRH-induced ACTH and cortisol response was significantly decreased to 47 and 71%, respectively. In conclusion, disturbances in the hypothalamic-pituitary-adrenal axis with an attenuated ACTH and cortisol response to CRH were found in subjects with night-eating syndrome.