Negative feedback inhibition

Acetyl-CoA carboxylase is an allosteric enzyme and is activated by citrate, which increases in concentration in the well-fed state and is an indicator of a plentiful supply of acetyl-CoA. Citrate converts the enzyme from an inactive dimer to an active polymeric form, having a molecular mass of several milhon. Inactivation is promoted by phosphorylation of the enzyme and by long-chain acyl-CoA molecules, an example of negative feedback inhibition by a product of a reaction. Thus, if acyl-CoA accumulates because it is not esterified quickly enough or because of increased lipolysis or an influx of free fatty acids into the tissue, it will automatically reduce the synthesis of new fatty acid. Acyl-CoA may also inhibit the mitochondrial tricarboxylate transporter, thus preventing activation of the enzyme by egress of citrate from the mitochondria into the cytosol. 

TOSKES p p (1986) Negative feedback inhibition of pancreatic exocrine secretion in humans. Adv Exp Med Biol. 199 143-52. 

Finasteride inhibits 5a-reductase, the enzyme converting T. into dihydrotestosterone (DHT). Thus, the androgenic stimulus is reduced in those tissues in which DHT is the active species (e.g., prostate). T.-dependent tissues or functions are not or hardly affected (e.g., skeletal muscle, negative feedback inhibition of gonadotropin secretion, and libido). Finasteride can be used in benign prostate hyperplasia to shrink the gland and, possibly, to improve micturition. 

Following the administration of a 0.25-mg dose of DEX, it was possible to observe that the cortisol response was accompanied by a concurrent decline in the number of cytosolic lymphocyte receptors (Yehuda et al. 1995a). This finding contrasted with the observation of a reduced decline in the number of cytosolic lymphocyte receptors in major depression, implying that the reduced cortisol levels following DEX administration may reflect an enhanced negative feedback inhibition in PTSD (Gormley et al. 1985). 

Results from these studies are expressed as the extent of cortisol suppression, evaluated by the quotient of 8 00 a.m. post-DEX cortisol to 8 00 a.m. basehne cortisol. Expressing the data in this manner accounts for individual differences in baseline cortisol levels and allows for a more precise characterization of the strength of negative feedback inhibition as a continuous rather than as a dichotomous variable. Whereas studies of major depression empha-... 

Whereas both the results of the DST and CCK challenge tests are consistent with the idea of an enhanced negative feedback inhibition in PTSD, these alter-... 

Although the neuroendocrine challenges described above directly assess ACTH and cortisol, hypothalamic CRF release may be inferred from some of the results. For example, because metyrapone administration results in the elimination of negative feedback inhibition, its administration allows an exploration of suprapituitary release of ACTH, without the potentially confounding effects of differing ambient cortisol levels. To the extent that metyrapone administration results in a substantially higher increase in ACTH and 11-deoxycortisol... 

Findings of the cortisol response to DEX are compatible with both the enhanced negative feedback inhibition model and adrenal insufficiency. However, in the latter case, one would not expect that a reduced cortisol level to result from, or even be accompanied by, changes in the GR, but rather, would reflect reduced adrenal output rather than an enhanced containment of ACTH. 

The LDL particle (10% triglyceride content) is finally taken up into the liver and other tissues by the LDL receptor. The LDL receptor is a six-domain transmembrane protein whose synthesis is under negative feedback regulation, such that when intracellular cholesterol levels are raised, new LDL receptors are not formed, thereby preventing the uptake of further cholesterol from plasma LDL. LDL also inhibits HMG-CoA reductase and hence cholesterol synthesis by negative feedback inhibition. Absence of the LDL receptor leads to hypercholesterol-aemia and atherosclerosis, as there is a decrease in the rate at which LDLs are removed from the plasma. 

An CL,-adrenoceptor blocker that spares the Oj-receptor so that negative feedback inhibition of noradrenaline release is maintained, is more useful in hypertension (less tachycardia and postural and... 

Biorhythms and other physiological events in the brain result in episodic and circadian secretion of CRH from the hypothalamus. Tliis in turn elicits similar circadian variation in ACTH release. Secreted ACTH then stimulates cortisol production, which provides negative feedback inhibition to the CRH-ACTH axis. The secretion of CRH, a 41-amino acid peptide, is modulated by neuroendocrine, physical, and emotional factors. Besides CRH, other circulating factors can have an influence on the secretory dynamics of ACTH release. Antidiuretic hormone from the... 

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