Hormones closed-loop feedback

FIGURE 41-1. Hypothalamic-pituitary-thyroid axis. Thyrotropinreleasing hormone (TRH) is synthesized in the neurons within the paraventricular nucleus of the hypothalamus. TRH is released into the hypothalamic-pituitary portal circulation and carried to the pituitary, where it activates the pituitary to synthesize and release thyrotropin (TSH). TSH activates the thyroid to stimulate the synthesis and secretion of thyroxine (T4) and triiodothyronine (T3). T4 and T3 inhibit TRH and TSH secretion, closing the feedback loop. 

A FIGURE 13-20 Localization of protein kinase A (PKA) to the nuclear membrane in heart muscle. This A kinase-associated protein mAKAP anchors both PKA and cAMP phosphodiesterase (PDE) to the nuclear membrane, maintaining them in a negative feedback loop that provides close local control of the cAMP level. Step D The basal level of PDE activity in the absence of hormone (resting state) keeps cAMP levels below those necessary for PKA activation. StepH Activation of p-adrenergic receptors causes an increase in cAMP level in... 

As pointed out by Rasmussen [201, 203] the stimulation of cyclic AMP is unidirectional. We know how it is produced, but we do not know how it is turned off after the cell response. We have seen many examples in which the ultimate product of a biological stimulus is inhibited by the initial stimulus thus closing what is called a feedback loop (see Inborn Errors— Hormones). Rasmussen believes that if the actions of calcium and cAMP are coupled, such a feedback loop can be achieved. Calcium concentrations in the extracellular fluid, the cytosol and the mitochondria are 10", 10" 10" molar respectively, thus the calcium... 

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