Feedback control, negative

Since amino adds are used as essential components of the microbial cells and their biosynthesis is regulated to maintain an optimal level, they are normally synthesised in feedback limited amounts and are subjed to negative feedback control. The main problem using control strains is, therefore, the production of minor amounts of amino adds at an early... 

Here Kc = 0 represents open loop conditions, Kc < 0 represents positive feed back conditions, and Kc > 0 represents conventional negative feedback control. 

When the concentration of the free form of a hormone decreases, then more of this hormone will be released from the binding proteins. The free hormone is the biologically active form. It binds to the target tissue to cause its actions and is involved with the negative feedback control of its secretion. The binding of hormones to plasma proteins has several beneficial effects, including ... 

Thyroid hormone production is regulated by TSH secreted by the anterior pituitary, which in turn is under negative feedback control by the circulating level of free thyroid hormone and the positive influence of hypothalamic thyrotropin-releasing hormone. Thyroid hormone production is also regulated by extrathyroidal deiodination of T4 to T3, which can be affected by nutrition, nonthyroidal hormones, drugs, and illness. 

The activation a2-adrenoceptors is particularly important in the negative feedback control of adrenergic outflow, centrally in the vasomotor centers and peripherally at the presynaptic axonal membrane of adrenergic neurons. 

Since the synthesis and release of cortisol are regulated by pituitary corticotrophin, removal of the pituitary gland results in decreased function and eventual atrophy of the zona fasciculata and zona reticularis. Infusion of supraphysiological concentrations of cortisol will suppress corticotrophin secretion from the pituitary and wUl markedly decrease circulating corticotrophin levels. This occurrence implies a negative feedback control for corticotrophin and corticosteroid release (Fig. 60.3). 

By a negative feedback control mechanism mediated by H2 receptors, histamine appears to modulate its own release and that of other mediators from sensitized mast cells in some tissues. In humans, mast cells in skin and basophils show this negative feedback mechanism lung mast cells do not. Thus, histamine may act to limit the intensity of the allergic reaction in the skin and blood. 

There are also a few examples of positive feedback mechanisms in the endocrine system.25 43 In a positive feedback loop, rising concentrations of one hormone cause an increase in other hormones, which, in turn, facilitates increased production of the first hormone. The primary example of this type of feedback occurs in the female reproductive system, where low levels of estrogen production increase the release of pituitary hormones (LH, FSH).10 43 Increased LH and FSH then facilitate further estrogen production, which further increases pituitary hormone secretion, and so on (see Chapter 30). Positive feedback mechanisms are relatively rare, however, compared with negative feedback controls in the endocrine system. 

FIGURE 28-1 Negative feedback control in the hypothalamic-pituitary-endocrine pathways. Excitatory and inhibitory effects are indicated by (+] and H, respectively. Negative feedback loops occur owing to inhibition of the endocrine hormone on the pituitary and hypothalamus. 

Cortisol also plays a role in controlling the release of CRH and ACTH from the hypothalamus and pituitary, respectively. As illustrated in Figure 29-2, the relationship between plasma cortisol and CRH and ACTH release is a classic example of a negative feedback control system. Increased plasma cortisol levels serve to inhibit subsequent release of CRH and ACTH, thus helping to maintain homeostasis by moderating glucocorticoid activity. 

FIGURE 29-2 Negative feedback control of glucocorticoid synthesis. Cortisol limits its own synthesis by inhibiting the release of corticotropin-releasing hormone [CRH] from the hypothalamus and adrenocorticotropic hormone [ACTH] from the anterior pituitary. 

Thyroid hormone release is subject to the negative feedback strategy that is typical of endocrine systems controlled by the hypothalamic-pituitary axis. Increased circulating levels of the thyroid hormones (T4, T3) serve to limit their own production by inhibiting TRH release from the hypothalamus and TSH release from the anterior pituitary.30,35 This negative feedback control prevents peripheral levels of thyroid hormones from becoming excessively high. 

The principle of negative feedback control is also found at the presynaptic level of autonomic function. Important presynaptic feedback inhibitory control mechanisms have been shown to exist at most nerve endings. A well-documented mechanism involves an 2 receptor located on noradrenergic nerve terminals. This receptor is activated by norepinephrine and similar molecules activation diminishes further release of norepinephrine from these nerve endings (Table 6-4). Conversely, a presynaptic Breceptor appears to facilitate the release of norepinephrine. Presynaptic receptors that respond to the transmitter substances released by the nerve ending are called autoreceptors. Autoreceptors are usually inhibitory, but many cholinergic fibers, especially somatic motor fibers, have excitatory nicotinic autoreceptors. 

Batchelor M, Schenk JO (1998) Protein kinase A activity may kinetically upregulate the striatal transporter for dopamine. J Neurosci 18 10304-9 Baumann PA, Waldmeier PC (1981) Further evidence for negative feedback control of serotonin release in the central nervous system. Naunyn-Schmiedeberg s Arch Pharmacol 317 36 13 Bean AJ, During MJ, Roth RH (1990) Effects of dopamine autoreceptor stimulation on the release of colocalized transmitters in vivo release of dopamine and neurotensin from rat prefrontal cortex. Neurosci Lett 108 143-8... 

Figure 18.3. Endocrine-immune inter-relationship in depression. In depression, the hypothalamic-pituitary-adrenal (HPA) axis is up-regulated with a down-regulation of its negative feedback controls. Corticotrophin releasing factor (CRF) is hypersecreted from the hypothalamus and induces the release of adrenocortico-trophic hormone (ACTH) from the pituitary. ACTH interacts with receptors on adrenocortical cells and cortisol is released from the adrenal glands adrenal hypertrophy can also occur. Release of cortisol into the circulation has a number of effects, including elevation of blood glucose. The negative feedback of cortisol to the hypothalamus, pituitary and immune system is impaired. This leads to continual activation of the HPA axis and excess cortisol release. Cortisol receptors become desensitized leading to increased activity of the pro-inflammatory immune mediators and disturbances in neurotransmitter transmission.

The TGF mechanism produces a negative feedback control on the rate of glomerular filtration. However, experiments performed on rats by Leyssac and Baumback [2] and by Leyssac and Holstein-Rathlou [3] in the 1980s demonstrated that the feedback regulation tends to be unstable and to generate large amplitude self-sustained oscillations in the proximal intratubular pressure with a period of 30-40 s. With different amplitudes and phases, similar oscillations have subsequently been observed in the distal intratubular pressure and in the chloride concentration near the terminal part of the loop of Henle [4],... 

The simplest form of regulation of a metabolic pathway is the inhibition of an enzyme by the product of the pathway. In Fig. 9-5, the E, s denote enzymes, A and B are metabolites, and the circled minus sign indicates inhibition. If there were no inhibitor of the enzyme (E,) acting on A, the concentration of B would depend entirely on its rate of synthesis or utilization. If the rate of utilization of B decreased or B was supplied from an outside source, its concentration would rise, perhaps even to toxic levels. However, if B is an inhibitor of the first enzyme, then as its concentration rises, the extent of inhibition will increase and its rate of synthesis will decrease. This effect is called feedback inhibition or negative feedback control it is a concept also used in describing electronic circuits. 

HMG-CoA reductase is under negative-feedback control by the sterol synthesis end products cholesterol and bile salts. The important indicator of HMG-CoA reductase is the blood cholesterol concentration, which is mostly determined by the presence of LDL particle. 

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