Thyrotropic feedback control: Evidence for an additional ultrashort feedback loop from fractal analysis

More than 70 years after the discovery of the pituitary-thyroid feedback control mechanism, a classical endocrine regulation system, most of its parameters have been identified. However, the regulation of its central component in the pituitary gland, probably responsible for pulsatile release of thyrotropin (TSH), remains obscure. In order to infer its structure from the system's behavior, four different pituitary models were created and compared regarding their fractal properties. Based on the simplest model showing noncompetitive inhibition of TSH release by thyroid hormones-a physiologically plausible correlation-one alternative model added stochastic stimulation by central signals and another added an additional intrapituitary feedback loop, whereas the fourth model combined both effects. This latter model combining noncompetitive inhibition with the two additional effects showed the same fractal dimensions as in vivo time series, whereas the simpler models yielded significantly lower time-series complexity. These results suggest that both stochastic stimulation and ultrashort loop feedback are involved in the generation of TSH pulses in the human pituitary.