Hormones inactivation

Fig. 4.3. Example of a tissue-specific hormone inactivation. Cortisol is enzymatically converted to an keto compound at the Cll position. The modified cortisol compound can no longer bind and activate the aldosterone receptor. Aldosterone can not be turned over by 11-P-dehydroge-nase because the OH group at position 11 forms a half-acetal with the formyl group (C18).

Similarly, concern about minute amounts of contaminants co-purified with human growth hormone extracted from brain tissues, which could lead to the development of Jacob-Kreutzfeld syndrome, inevitably resulted in the development of recombinant human growth hormone. Inactivated hepatitis B particles isolated from hepatitis B-positive patients were originally used to prevent hepatitis B virus infection, but a small fraction of individuals became infected through vaccination. When the hepatitis B surface antigen was... 

Clayton RN, Shakespear RA, Duncan JA, Marshall JC (1979) Luteinizing hormone-releasing hormone inactivation by purified pituitary plasma membranes Effects on receptorbinding studies. Endocrinology 104 1484-1494... 

Protein handling Carbohydrate handling Lipid handling Bile and bilirubin handling Hormone inactivation Drug metabolism Immunological function... 

Williams DR, Fisher MJ, Rees HH. Characterization of ecdysteroid 26-hydroxy-lase An enzyme involved in molting hormone inactivation. Arch Biochem Biophys 2000 376 389-98. 

Smooth muscle contractions are subject to the actions of hormones and related agents. As shown in Figure 17.32, binding of the hormone epinephrine to smooth muscle receptors activates an intracellular adenylyl cyclase reaction that produces cyclic AMP (cAMP). The cAMP serves to activate a protein kinase that phosphorylates the myosin light chain kinase. The phosphorylated MLCK has a lower affinity for the Ca -calmodulin complex and thus is physiologically inactive. Reversal of this inactivation occurs via myosin light chain kinase phosphatase. 

Increased lipid synthesis/inhibi-tion of lipolysis Activation of lipoprotein lipase (LPL)/induc-tion of fatty acid synthase (FAS)/inactivation of hormone sensitive lipase (HSL) Facilitated uptake of fatty acids by LPL-dependent hydrolysis of triacylglycerol from circulating lipoproteins. Increased lipid synthesis through Akt-mediated FAS-expression. Inhibition of lipolysis by preventing cAMP-dependent activation of HSL (insulin-dependent activation of phosphodiesterases )... 

Bovine growth hormone, a difficult protein for which to develop controlled release systems due to its propensity toward self-aggregation and inactivation, has successfully been incorporated into polyanhydride matrices (18). The growth hormone was colyophilized with sucrose, dry-mixed with finely powdered polyanhydride, and then compression molded into 1.4-cm-diaraeter wafers, 1 mm thick. As is shown in Fig. 15, release of bovine growth hormone was well controlled over a prolonged period of time. The assay for bovine... 

In adipose tissue, the effect of the decrease in insulin and increase in glucagon results in inhibition of lipo-genesis, inactivation of lipoprotein lipase, and activation of hormone-sensitive lipase (Chapter 25). This leads to release of increased amounts of glycerol (a substrate for gluconeogenesis in the liver) and free fatty acids, which are used by skeletal muscle and liver as their preferred metabolic fuels, so sparing glucose. 

The metabolism (activation or inactivation) of the hormone in the target cell. 

Phytoestrogens may also modulate the concentration of endogenous steroid hormones by binding to and inactivating the enzymes involved in their biosynthesis and metabolism. 

Isoflavones have been implicated in goiter induction. Soybean extracts inhibit reactions catalyzed by thyroid peroxidase (TPO), essential to the synthesis of thyroid hormones (Divi et al., 1997). Genistein and daidzein (at about 1-10 p,M of IC50) may act as alternative substrates for tyrosine iodination (Divi et al., 1997). Furthermore, genistein and daidzein have also been shown to cause the irreversible inactivation of TPO in the presence of hydrogen peroxide. Genistein also inhibits thyroxine synthesis in the presence of iodinated... 

Sustained- and controlled-release devices for drug delivery in the vaginal and uterine areas are most often for the delivery of contraceptive steroid hormones. The advantages in administration by this route—prolonged release, minimal systemic side effects, and an increase in bioavailability—allow for less total drug than with an oral dose. First-pass metabolism that inactivates many steroid hormones can be avoided [183,184],... 

The regulation of fat metabolism is relatively simple. During fasting, the rising glucagon levels inactivate fatty acid synthesis at the level of acetyl-CoA carboxylase and induce the lipolysis of triglycerides in the adipose tissue by stimulation of a hormone-sensitive lipase. This hormone-sensitive lipase is activated by glucagon and epinephrine (via a cAMP mechanism). This releases fatty acids into the blood. These are transported to the various tissues, where they are used. 

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