Circadian clock control of endocrine factors

Abstract

Organisms experience dramatic fluctuations in demands and stresses over the course of the day. In order to maintain biological processes within physiological boundaries, mechanisms have evolved for anticipation of, and adaptation to, these daily fluctuations. Endocrine factors have an integral role in homeostasis. Not only do circulating levels of various endocrine factors oscillate over the 24 h period, but so too does responsiveness of target tissues to these signals or stimuli. Emerging evidence suggests that these daily endocrine oscillations do not occur solely in response to behavioural fluctuations associated with sleep-wake and feeding-fasting cycles, but are orchestrated by an intrinsic timekeeping mechanism known as the circadian clock. Disruption of circadian clocks by genetic and/or environmental factors seems to precipitate numerous common disorders, including the metabolic syndrome and cancer. Collectively, these observations suggest that strategies designed to realign normal circadian rhythmicities hold potential for the treatment of various endocrine-related disorders.

Figure 1

Time-of-day at which circulating levels of key endocrine factors peak in humans. Abbreviations utilized include: GH, growth hormone; TSH, thyroid stimulating hormone; PRL, prolactin; T₃, triiodothyronine; RAAS, renin-angiotensin-aldosterone system; FGF21, fibroblast growth factor 21; (F), females only; (M), males only.

Figure 2

SCN and non-SCN derived entrainment of peripheral circadian clocks (A) and the impact of cell autonomous circadian clocks on endocrine factor release and sensitivity (B). As discussed in the text, peripheral circadian clocks are entrained (re-set) by both SCN- (e.g., prokineticin 2, neural stimulation) and behavior- (e.g., feeding, physical activity) dependent influences (A). Circadian clocks within the adrenal cortex contribute to diurnal variations in cortisol release, through modulating sensitivity to ACTH, while the β-cell circadian clock is appears to be similarly critical for insulin secretion (B). In addition, circadian clocks within target tissues (e.g., adipose, liver, skeletal muscle) potentially modulate sensitivity to endocrine factors in a time-of-day-dependent manner (B).

Figure 2

SCN and non-SCN derived entrainment of peripheral circadian clocks (A) and the impact of cell autonomous circadian clocks on endocrine factor release and sensitivity (B). As discussed in the text, peripheral circadian clocks are entrained (re-set) by both SCN- (e.g., prokineticin 2, neural stimulation) and behavior- (e.g., feeding, physical activity) dependent influences (A). Circadian clocks within the adrenal cortex contribute to diurnal variations in cortisol release, through modulating sensitivity to ACTH, while the β-cell circadian clock is appears to be similarly critical for insulin secretion (B). In addition, circadian clocks within target tissues (e.g., adipose, liver, skeletal muscle) potentially modulate sensitivity to endocrine factors in a time-of-day-dependent manner (B).