Negative-feedback regulation

The major FSH target in the male is the Sertoli cells, found in the walls of the seminiferous tubules of the testis. They function to anchor and nourish the spermatids, which subsequently are transformed into spermatozoa during the process of spermatogenesis. Sertoli cells also produce inhibin (discussed later), which functions as a negative feedback regulator of FSH. The major physiological effect of FSH in the male is thus sperm cell production. 

Serizawa, S. et al. Negative feedback regulation ensures the one receptor-one olfactory neuron rule in mouse. Science 302 2088-2094,2003. 

Because of the negative feedback regulation of thyroid function, thyroid activation can be inhibited by administration of T4 doses equivalent to the endogenous daily output (approx. 150 pg/d). Deprived of stimulation, the inactive thyroid regresses in size. 

Negative feedback. Regulation of a reaction or a pathway by the end product. 

In the rat anaphylactic histamine release from peritoneal mast cells is reduced by (R)a-methylhistamine, and this effect is reversed by thioperamide. Therefore, H3 receptors seem to be responsible for the negative feedback regulation of histamine release from rat peritoneal mast cells. However, the high concentrations of the H3 agonist necessary to elicit this effect, suggest that H3 receptors on the rat peritoneal mast cells are a subtype distinct from those in the rat brain. Contrastingly, histamine release induced by compound 48/80 was not altered by H3 ligands (Kohno et al., 1994). 

Weib C, Kolluri SK, Kiefer F, et al. 1996. Complementation of Ah receptor deficiency in hepatoma cells negative feedback regulation and cell cycle control by the Ah receptor. Exp Cell Res 226 154-163. 

Nickenig, G., Strehlow, K., Baumer, A. T., et al. 2000. Negative feedback regulation of reactive oxygen species on ATI receptor gene expression. Br J Pharmacol 131 795-803. 

Stroschein, S.L., Wang, W., Zhou, S., Zhou, Q., and Luo, K. 1999. Negative feedback regulation of TGF-beta signaling by the SnoN oncoprotein. Science 286 771-774. 

The nonlinearity of (11.8) comes from the terms 4>(z°(t)) and y (r) 2 (r) involved in the nonlinear negative feedback regulation. What we want to do is replace these nonlinear terms by a linear function in the vicinity of the equilibrium state (x, y, z ). This involves writing the Jacobian matrix of the linearized system (cf. Appendix A) ... 

The increase in 24-OHase by l,25-(OH)2D3 is further sensitized by phorbol esters [138], indicating the involvement of protein kinase C [139, 140], However, it is unclear whether protein kinase C functions in conjunction with l,25-(OH)2D3 by a modification of the ferredoxin subunit [139] or by a direct modification of the expression of the 24-OHase cytochrome P450 [138, 140], In addition, l,25-(OH)2D3 serves a negative feedback regulation on the la-OHase system [72], The molecular details of this regulation are completely unknown to date. 

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. 

Watson SP, and Lapetina EG. (1983). ,2-Diacylglycerol and phorbol ester inhibit agraiist-induced formation of inositol idiosphates in human platelets. Possible in lications for negative feedback regulation of inositol ospholipid hydrolysis. Proc. Natl. Acad. Sci. U.S.A. 82,2623-2626. 

Inhibins are members of the transforming growth factor (3 (TGF(3) superfamily of proteins. Inhibin forms include inhibin A and B, and activin A, B, and AB. As described in Chapter 53, inhibin is a negative feedback regulator of FSH secretion in both males and females. The placenta produces large quantities of inliibin A that completely suppress FSH. 

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