An optimization formulation for characterization of pulsatile cortisol secretion

Abstract

Cortisol is released to relay information to cells to regulate metabolism and reaction to stress and inflammation. In particular, cortisol is released in the form of pulsatile signals. This low-energy method of signaling seems to be more efficient than continuous signaling. We hypothesize that there is a controller in the anterior pituitary that leads to pulsatile release of cortisol, and propose a mathematical formulation for such controller, which leads to impulse control as opposed to continuous control. We postulate that this controller is minimizing the number of secretory events that result in cortisol secretion, which is a way of minimizing the energy required for cortisol secretion; this controller maintains the blood cortisol levels within a specific circadian range while complying with the first order dynamics underlying cortisol secretion. We use an ℓ0-norm cost function for this controller, and solve a reweighed ℓ1-norm minimization algorithm for obtaining the solution to this optimization problem. We use four examples to illustrate the performance of this approach: (i) a toy problem that achieves impulse control, (ii) two examples that achieve physiologically plausible pulsatile cortisol release, (iii) an example where the number of pulses is not within the physiologically plausible range for healthy subjects while the cortisol levels are within the desired range. This novel approach results in impulse control where the impulses and the obtained blood cortisol levels have a circadian rhythm and an ultradian rhythm that are in agreement with the known physiology of cortisol secretion. The proposed formulation is a first step in developing intermittent controllers for curing cortisol deficiency. This type of bio-inspired pulse controllers can be employed for designing non-continuous controllers in brain-machine interface design for neuroscience applications.

Application of FT-IR spectroscopy to assess physiological stress in rugby players during fatigue test

“…Thus, the specific conditions that elevate cortisol concentrations also have the potential to influence the variety of critical physiological processes that can be affected by hypothalamic-pituitary-adrenocortical axis activity (Dickerson and Kemeny, 2004). In this study, saliva collection was performed at 7:00 am, due to salivary cortisol circadian rhythm, in which levels increase dramatically on awakening and gradually decrease throughout the day, reaching the lowest levels late in the evening (Faghih et al, 2015).…”

Invisible Designers: Brain Evolution Through the Lens of Parasite Manipulation

“…Moreover, pulsed signals can encode more information by exploiting both frequency (timing of pulses) and amplitude modulation (amount released per pulse). Some models also suggest that pulsatile secretion can also be more energy efficient than continuous release (Walker et al 2010;Faghih et al 2015). In summary, pulsatile signaling has no shortage of potential advantages.…”

Design of Intermittent Control for Cortisol Secretion Under Time-Varying Demand and Holding Cost Constraints

“…However, pulsatile signaling is much less understood since it is significantly different from continuous signaling [25]. Therefore, there is a great need to understand the physiology underlying the pulsatile hormone release [9].…”

“…Cortisol is a steroid hormone that is mainly responsible for regulating metabolism and the body's reaction to stress and inflammation [1]. It is known that the mechanisms of the HPA axis are governed not only by a circadian rhythm, but also by an ultradian pattern of pulsatile release of cortisol [1,7,9,34,37,38]. The pulsatile release of cortisol from the adrenal glands is triggered and controlled by a hierarchical system involving corticotropinreleasing hormone (CRH) from the hypothalamus, adrenocorticotropic hormone (ACTH) from the anterior pituitary, and cortisol from the adrenal glands [1,7,26,29].…”

“…Due to ethical reasons, direct measurement of endocrine glands (e.g., CRH) cannot be made for healthy humans [34]. One may have to rely on reasonable theoretical models to understand the sophisticated control mechanisms, which involves (i) determining the number, timing and amplitude of cortisol pulses, socalled "secretory events", to better understand the physiology, effects of drugs and other interventions [6,8]; (ii) designing intermittent controllers to optimally control cortisol levels (i.e., minimizing the number of secretory events as well as maintaining the blood cortisol levels within bounds that satisfy circadian demand and cost constraints) linked to cortisol pulsatility [6,9]. The latter might be useful in treating, e.g., Addisonian disease which is caused by the adrenal deficiency.…”