Pulsatile Glucocorticoid Secretion: Origins and Downstream Effects
Autor: | Steven E. Calvano, Ioannis P. Androulakis, Jeremy D. Scheff, Stephen F. Lowry, Alyssa K. Kosmides |
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Rok vydání: | 2011 |
Předmět: |
Hypothalamo-Hypophyseal System
Periodicity medicine.medical_specialty Biomedical Engineering Pulsatile flow Pituitary-Adrenal System Biology Models Biological Glucocorticoid receptor Internal medicine medicine Animals Humans Glucocorticoids Ultradian rhythm Adrenal gland Systems Biology Rats Glucocorticoid secretion medicine.anatomical_structure Endocrinology Signal transduction hormones hormone substitutes and hormone antagonists Glucocorticoid medicine.drug Hormone |
Zdroj: | IEEE Transactions on Biomedical Engineering. 58:3504-3507 |
ISSN: | 1558-2531 0018-9294 |
DOI: | 10.1109/tbme.2011.2162236 |
Popis: | Glucocorticoids are steroid hormones which, among other functions, exert an antiinflammatory effect. Endogenous glucocorticoids are normally secreted by the adrenal gland in discrete bursts. It is becoming increasingly evident that this pulsatile secretion pattern, leading to ultradian rhythms of plasma glucocorticoid levels, may have important downstream regulatory effects on glucocorticoid-responsive genes. Mathematical modeling of this system can compliment recent experimental data and quantitatively evaluate hypothesized mechanistic underpinnings of differential pulsatile signal transduction. In this paper, we describe an integrated model of pulsatile secretion of glucocorticoids by the hypothalamic-pituitary-adrenal (HPA) axis and the pharmacodynamic effect of glucocorticoids. This model is used to investigate the difference in transcriptional responses to pulsatile and constant glucocorticoid exposure. Nonlinearity in ligand-receptor kinetics leads to the differential expression of glucocorticoid-responsive genes in response to different patterns of glucocorticoid secretion, even when the total amount of glucocorticoid exposure is held constant. Understanding the implications of ultradian rhythms in glucocorticoids is important in studying the dysregulation of HPA axis function leading to altered glucocorticoid secretion patterns in disease. |
Databáze: | OpenAIRE |
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