title: Computer simulation of factors involved in the down-regulation of hormonal effects.
abstract: Down-regulation of hormonal effects is in the presented simulation related to the number of functional receptors and quantity of available hormonal stimulation. The former is in the model substituted with the quantity of stimulation able to produce a full down-regulation (Hs100) of target cells. The halftime (t1/2) of the hormonal effect recovery means the interval before the second hormonal stimulation can elicit half of the initial hormonal effect. Recovered hormonal effects are calculated after periods of two, three, four and five t1/2. The interval among hormonal stimulations varied from 1/2 to 5/2 of t1/2. Shorter than t1/2 intervals showed profound down-regulation even at weak hormonal stimulations (> 20% of Hs100). Stable levels of hormonal effects after frequent hormonal stimulations are found only in cases of very weak stimulations (< 10% of Hs100). Intervals equalling t1/2 among weak stimulations (< 20% Hs100) produced stable hormonal effects. Further prolongation among repeated stimulations improved stability of hormonal effects and even strong stimulations (> 60% of Hs100) were followed with only temporary profound down-regulation. Hormone-binding receptors unable to activate target cells are in the model described as defective. Probability for the target cell to be stimulated is in the model defined as P. Relative quantity of hormonal stimulation per target cell needed to achieve certain P is calculated for cells bearing different proportions of defective receptors. Activation following weak hormone stimulations is highly probable (> 90%) for cells bearing less than 30% of defective receptors. With the proportion of defective receptors over 60%, the activation probability after weak hormone stimulations is reduced (< 66%). Down-regulation can be considered as a modulator of hormonal effects. In prediabetic patients, intense stimulation of pancreatic insulin secretion by frequent or increased ingestion of carbohydrates might lead to sustained hyperinsulinemia. A substantial portion of the target tissue would become down-regulated with increased number of defective insulin receptors. Poor glucose utilization in the down-regulated tissue with resultant hyperglycemia would further stimulate insulin secretion until failure. Reduced tissue transportability of large hormone molecules, such as hGH, or proinsulin, can make their effects more pronounced in the perivascular space. Circulating hormone binding proteins or the basal membrane thickening in small vessels can further decrease the hormonal effects on more remote cells. Physical activity in IDDM patients increases insulin effect. Possible explanation is that increased muscle perfusion is making more insulin available to the less down-regulated skeletal muscle cells.
authors.affiliation: Department of Oncology, Osijek Clinical Hospital.
authors.forename: S
authors.initials: S
authors.lastname: Kurbel
authors.forename: B
authors.initials: B
authors.lastname: Kurbel
authors.forename: M
authors.initials: M
authors.lastname: Dicić
authors.forename: V
authors.initials: V
authors.lastname: Ugraji
mesh_terms: D003198:Computer Simulation; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D004040:Dietary Carbohydrates / Q000008:administration & dosage / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology*; D015444:Exercise / Q000502:physiology; D006728:Hormones / Q000502:physiology*; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology; D006946:Hyperinsulinism / Q000503:physiopathology; D007328:Insulin / Q000502:physiology; D007515:Islets of Langerhans / Q000502:physiology; D018482:Muscle, Skeletal / Q000502:physiology; D011236:Prediabetic State / Q000503:physiopathology; D011956:Receptors, Cell Surface / Q000502:physiology*
chemical_list: D004040:Dietary Carbohydrates; D006728:Hormones; D007328:Insulin; D011956:Receptors, Cell Surface