Evidence for a Coupled Oscillator Model of Endocrine Ultradian Rhythms

Abstract

Whereas long-period temporal structures in endocrine dynamics have been well studied, endocrine rhythms on the scale of hours are relatively unexplored. The study of these ultradian rhythms (URs) has remained nascent, in part, because a theoretical framework unifying ultradian patterns across systems has not been established. The present overview proposes a conceptual coupled oscillator network model of URs in which oscillating hormonal outputs, or nodes, are connected by edges representing the strength of node-node coupling. We propose that variable-strength coupling exists both within and across classic hormonal axes. Because coupled oscillators synchronize, such a model implies that changes across hormonal systems could be inferred by surveying accessible nodes in the network. This implication would at once simplify the study of URs and open new avenues of exploration into conditions affecting coupling. In support of this proposed framework, we review mammalian evidence for (1) URs of the gut-brain axis and the hypothalamo-pituitary-thyroid, -adrenal, and -gonadal axes, (2) UR coupling within and across these axes; and (3) the relation of these URs to body temperature. URs across these systems exhibit behavior broadly consistent with a coupled oscillator network, maintaining both consistent URs and coupling within and across axes. This model may aid the exploration of mammalian physiology at high temporal resolution and improve the understanding of endocrine system dynamics within individuals.

Ultradian Rhythms in Heart Rate Variability and Distal Body Temperature Anticipate the Luteinizing Hormone Surge Onset

“…Such a finding would further support the notion that the state of one system (e.g., reproductive) can be inferred via measurements of another (e.g., autonomic or metabolic) (Shannahoff-Khalsa et al, 1996;Grant et al, 2018;Goh et al, 2019). Perhaps the most consistent biological rhythmic changes across the menstrual cycle occur at the 1-4 h (ultradian) timescale (Brandenberger et al, 1987;Shannahoff-Khalsa et al, 1996, 1997Grant et al, 2018;Zavala et al, 2019). Most elements of the hypothalamic-pituitary-ovarian axis, including gonadotropin releasing hormone (GnRH) (Clarke et al, 1987;Moenter et al, 1991;Gore et al, 2004), luteinizing hormone (LH) (Backstrom et al, 1982;Vugt et al, 1984;Rossmanith et al, 1990), FSH (Yen et al, 1972;Genazzani et al, 1993;Booth Jr et al, 1996;Pincus et al, 1998), estradiol (Backstrom et al, 1982;Licinio et al, 1998), progesterone (Backstrom et al, 1982;Filicori et al, 1984;Veldhuis et al, 1988;Soules et al, 1989;Rossmanith et al, 1990;Genazzani et al, 1991) and testosterone (Nóbrega et al, 2009) show ultradian rhythms (URs) that are coordinated with menstrual phase (Grant et al, 2018).…”

“…The premise of the present investigation is that the presence of structured changes to peripheral biological rhythms across the menstrual cycle may allow for anticipation of the LH surge. Such a finding would further support the notion that the state of one system (e.g., reproductive) can be inferred via measurements of another (e.g., autonomic or metabolic) (Shannahoff-Khalsa et al, 1996;Grant et al, 2018;Goh et al, 2019). Perhaps the most consistent biological rhythmic changes across the menstrual cycle occur at the 1-4 h (ultradian) timescale (Brandenberger et al, 1987;Shannahoff-Khalsa et al, 1996, 1997Grant et al, 2018;Zavala et al, 2019).…”

“…Unfortunately, the most widely used form of contraception, female hormonal contraception, has short and long term risks for many users, including but not limited to increased breast cancer rate (Mørch et al, 2017;Marsden, 2017), luteal phase deficiency (Gnoth et al, 2002), dysmenorrhea (Delbarge et al, 2002;Gnoth et al, 2002), altered cognition (Pletzer & Kerschbaum, 2014;Bradshaw et al, 2020) and depressed mood (Skovlund et al, 2016(Skovlund et al, , 2018. These risks, combined with increasing recognition that physiological systems vary in a structured manner across the menstrual cycle (Brar et al, 2015;Smarr et al, 2016Smarr et al, , 2017Grant et al, 2018), provide the impetus to develop FAM approaches that employ high-temporalresolution, non-invasive measures of physiology.…”

“…Perhaps the most consistent biological rhythmic changes across the menstrual cycle occur at the 1-4 h (ultradian) timescale (Brandenberger et al, 1987;Shannahoff-Khalsa et al, 1996, 1997Grant et al, 2018;Zavala et al, 2019). Most elements of the hypothalamic-pituitary-ovarian axis, including gonadotropin releasing hormone (GnRH) (Clarke et al, 1987;Moenter et al, 1991;Gore et al, 2004), luteinizing hormone (LH) (Backstrom et al, 1982;Vugt et al, 1984;Rossmanith et al, 1990), FSH (Yen et al, 1972;Genazzani et al, 1993;Booth Jr et al, 1996;Pincus et al, 1998), estradiol (Backstrom et al, 1982;Licinio et al, 1998), progesterone (Backstrom et al, 1982;Filicori et al, 1984;Veldhuis et al, 1988;Soules et al, 1989;Rossmanith et al, 1990;Genazzani et al, 1991) and testosterone (Nóbrega et al, 2009) show ultradian rhythms (URs) that are coordinated with menstrual phase (Grant et al, 2018). Across species, patterns of these neuropeptides and hormones exhibit an increase in ultradian frequency and inter-hormone coupling strength leading up to ovulation (Rossmanith et al, 1990;Moenter et al, 1991) and a decrease in ultradian frequency and stability in the luteal phase (Backstrom et al, 1982;Healy et al, 1984;Filicori et al, 1984;Vugt et al, 1984;Rossmanith et al, 1990;Genazzani et al, 1991;Moenter et al, 1991;Licinio et al, 1998).…”

Feasibility of continuous fever monitoring using wearable devices

“…To date, most wearables do not use temperature sensors. This should be re-examined, as temperature contains rich physiological information (8,(22)(23)(24); distal temperature is not well mapped, but has been shown to include cues to context like daily and ultradian rhythms (23). Moreover, the relationships across individual variables through time are not simple linear functions, and so inference of one from another (as in, projecting fevers from HR) is not a trivial problem.…”