TY - JOUR

T1 - Modeling pulsativity in the hypothalamic–pituitary–adrenal hormonal axis

AU - Churilov, Alexander N.

AU - Milton, John G.

PY - 2022/12

Y1 - 2022/12

N2 - A new mathematical model for biological rhythms in the hypothalamic–pituitary–adrenal (HPA) axis is proposed. This model takes the form of a system of impulsive time-delay differential equations which include pulsatile release of adrenocorticotropin (ACTH) by the pituitary gland and a time delay for the release of glucocorticoid hormones by the adrenal gland. Numerical simulations demonstrate that the model’s response to periodic and circadian inputs from the hypothalamus are consistent with those generated by recent models which do not include a pulsatile pituitary. In contrast the oscillatory phenomena generated by the impulsive delay equation mode occur even if the time delay is zero. The observation that the time delay merely introduces a small phase shift suggesting that the effects of the adrenal gland are “downstream” to the origin of pulsativity. In addition, the model accounts for the occurrence of ultradian oscillations in an isolated pituitary gland. These observations suggest that principles of pulse modulated control, familiar to control engineers, may have an increasing role to play in understanding the HPA axis.

AB - A new mathematical model for biological rhythms in the hypothalamic–pituitary–adrenal (HPA) axis is proposed. This model takes the form of a system of impulsive time-delay differential equations which include pulsatile release of adrenocorticotropin (ACTH) by the pituitary gland and a time delay for the release of glucocorticoid hormones by the adrenal gland. Numerical simulations demonstrate that the model’s response to periodic and circadian inputs from the hypothalamus are consistent with those generated by recent models which do not include a pulsatile pituitary. In contrast the oscillatory phenomena generated by the impulsive delay equation mode occur even if the time delay is zero. The observation that the time delay merely introduces a small phase shift suggesting that the effects of the adrenal gland are “downstream” to the origin of pulsativity. In addition, the model accounts for the occurrence of ultradian oscillations in an isolated pituitary gland. These observations suggest that principles of pulse modulated control, familiar to control engineers, may have an increasing role to play in understanding the HPA axis.

KW - Adrenocorticotropic Hormone/metabolism

KW - Circadian Rhythm/physiology

KW - Glucocorticoids

KW - Hypothalamo-Hypophyseal System/metabolism

KW - Pituitary-Adrenal System/metabolism

UR - https://www.mendeley.com/catalogue/b41de107-097d-3bee-9d6f-a2d0c16bf163/

UR - http://www.scopus.com/inward/record.url?scp=85130275979&partnerID=8YFLogxK

U2 - 10.1038/s41598-022-12513-w

DO - 10.1038/s41598-022-12513-w

M3 - Article

C2 - 35589935

VL - 12

SP - 8480

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 8480

ER -