Role of Circadian Neuroendocrine Rhythms in the Control of Behavior and Physiology

Abstract

Hormones play a major role in regulating behavior and physiology, and their efficacy is often dependent on the temporal pattern in which they are secreted. Significant insights into the mechanisms underlying rhythmic hormone secretion have been gained from transgenic rodent models, suggesting that many of the body’s rhythmic functions are regulated by a coordinated network of central and peripheral circadian pacemakers. Some neuroendocrine rhythms are driven by transcriptional-posttranslational feedback circuits comprising ‘core clock genes’, while others represent a cyclic cascade of neuroendocrine events. This review focuses on recent data from the rhesus macaque, a non-human primate model with high clinical translation potential. With primary emphasis on adrenal and gonadal steroids, it illustrates the rhythmic nature of hormone secretion, and discusses the impact that fluctuating hormone levels have on the accuracy of clinical diagnoses and on the design of effective hormone replacement therapies in the elderly. In addition, this minireview raises awareness of the rhythmic expression patterns shown by many genes, and discusses how this could impact interpretation of data obtained from gene profiling studies, especially from nocturnal rodents.

Hormone Supplementation During Aging: How Much and When?

“…10,11,14 As expected, when we administered T to the old animals, their plasma T levels increased to young levels within an hour of oral administration. Due to the relatively high clearance rate of testosterone, this elevation was not sustained throughout the night; however, plasma levels of dihydrotestosterone (DHT), the more active metabolite of T, closely resembled that of young males after T administration (data not shown).…”

“…Similarly, we suspended the DHEA in sesame oil (2 mg/mL) and mixed it with chocolate or placed it inside a cookie. Our preliminary studies indicated that a single administration of DHEA failed to produce a sustained elevation of circulating DHEAS, confirming that the single-dose DHEA paradigm used in the premenopausal females was not ideal at reproducing the sustained elevation of DHEAS that is typically observed in young animals 9,10 ; in contrast, the plasma DHEAS levels resulting from the new doubledose DHEA supplementation paradigm closely followed those of the young control males.…”

“…Third, the dose and time of DHEA administration may have been suboptimal for accurately recreating the youthful pattern of DHEA and DHEAS in the circulation. 9,10 To address all three of these concerns, we developed a novel oral hormone supplementation paradigm to further investigate the efficacy of steroid treatment on cognition in the aged. We used aged male rhesus macaques to avoid the confounding effect of variable E 2 concentrations across the menstrual cycle.…”

Seasonal variation of haemoglobin A1c in a Portuguese adult population

“…Some, as blood pressure levels, heart rate, lipid profile, insulin and cortisol serum levels are also factors associated to the development of many diseases and cardiovascular events (5)(6)(7)(8)(9). Seasonal changes on type 1 diabetes incidence have also been reported in literature, with new onset cases diagnosed more commonly during winter months (10).…”

Age-related changes in neuroendocrine rhythmic function in the rhesus macaque

“…These rhythms have a period of approximately 24 h and are regulated by a highly coordinated circadian neuroendocrine mechanism that comprises three major components: (1) photoreception by the retina and transmission of neural signals along the retinohypothalamic tract, (2) integration of photoperiodic information with an internal reference circadian pacemaker located in the suprachiasmatic nucleus (SCN) of the hypothalamus, and (3) dissemination of synchronized circadian information to target organs, via the autonomic nervous system and through humoral pathways, and integration with local oscillator circuits (Okamura 2004;Karatsoreos and Silver 2007;Maywood et al 2007;Mendoza and Challet 2009;Bonnefont 2010;Urbanski 2011b). When functioning correctly, this mechanism ensures that various internal biochemical processes are compartmentalized not just spatially but also temporally and that physiological functions and behaviors occur at an appropriate time of day (Lemos et al 2006;Kalsbeek et al 2006).…”