Inhibitors of Hormone Synthesis

It has been suggested that potassium perchlorate should be used in the treatment of type 1 hyperthyroidism and glucocorticoids in the treatment of type 2 (SEDA-21, 199). Since hypothyroidism due to amiodarone tends to occur in areas in which there is sufficient iodine in the diet, it has been hypothesized that an iodinated organic inhibitor of hormone synthesis is formed and that the formation of this inhibitor is inhibited by perchlorate to a greater extent than thyroid hormone iodination is inhibited, since the iodinated lipids that are thought to be inhibitors require about 10 times more iodide than the hormone. However, there is a high risk of recurrence after treatment with potassium perchlorate, and it can cause serious adverse effects (SED-13,1281). 

Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) are members of a family of so-called natriuretic peptides, synthesized predominantly in the cardiac atrium, ventricle, and vascular endothelial cells, respectively (G13, Y2). ANP is a 28-amino-acid polypeptide hormone released into the circulation in response to atrial stretch (L3). ANP acts (Fig. 8) on the kidney to increase sodium excretion and glomerular filtration rate (GFR), to antagonize renal vasoconstriction, and to inhibit renin secretion (Ml). In the cardiovascular system, ANP antagonizes vasoconstriction and shifts fluid from the intravascular to the interstitial compartment (G14). In the adrenal cortex, ANP is a powerful inhibitor of aldosterone synthesis (E6, N3). At the hypothalamic level, ANP inhibits vasopressin secretion (S3). It has been shown that some of the effects of ANP are mediated via a newly discovered hormone, called adreno-medullin, controlling fluid and electrolyte homeostasis (S8). The diuretic and blood pressure-lowering effect of ANP may be partially due to adrenomedullin (V5). 

Schimmer, B.P. and Parker, K.L., Adrenocorticotropic hormone adrenocortical steroids and their synthetic analogs inhibitors of the synthesis and actions of adrenocortical hormones, in Goodman and Gilman s The Pharmacological Basis of Therapeutics, 9th ed., Hardman, J.G. and Limbird, L.E., Eds., McGraw-Hill, New York, 1996, chap. 59. 

Serotonin is synthesized via tryptophan and 5-hydroxytryptophan with decarboxylation of the latter (Fig. 25-12). Within the pineal body of the brain and in the retina, serotonin is acetylated to N-acetylseroto-nin,782/783 which is then O-methylated to melatonin, the pineal hormone (Fig. 25-12). A specific inhibitor of serotonin synthesis is p-chlorophenylalanine, and studies with this and other inhibitors suggest that serotonin is required for sleep.784... 

Schimmer BP, Parker KL. Adrenocorticotropic hormone adrenocortical steroids and their synthetic analogs inhibitors of the synthesis and actions of adrenocortical hormones. In Brunton LL, et al, eds. 

Schimmer BP, Parker KL (1995) Adrenocorticotropic Hormone Adrenocortical Steroids and Their Synthetic Analogs Inhibitors of the Synthesis and Actions of Adrenocortical Hormones. In Hardman JG, Limbird LE (eds) Goodman Gilman s The Pharmacological Basis of Therapeutics, 9th Edition. McGraw-Hill, New York, pp 1459-1485 Sullivan AT, Kinter LB (1995) Status of safety pharmacology in the pharmaceutical industry 1995. Drug Dev Res 35 166-172... 

Induction of de novo synthesis of a-amylase by GA in isolated aleurone layers is evident after a lag period of approximately 8 hr following administration of the hormone. In keeping with hormone responses generally, GA must be present continuously if the de novo synthesis of hydrolases is to be sustained. Synthesis of new RNA is essential to the GA-induction of de novo synthesis of hydrolases. Actinomycin D, an inhibitor of RNA synthesis, inhibits the synthesis and release of a-amylase if the inhibitor is presented during the first 7 to 8 hr after treatment. Inhibitors of protein synthesis, such as cycloheximide, also inhibit GA-induction of hydrolases. And, interestingly, abscisic acid, a growth-inhibiting hormone, inhibits GA-induced a-amylase synthesis as well. 

ADRENOCORTICAL STEROIDS AND THEIR SYNTHETIC ANALOGS INHIBITORS OF THE SYNTHESIS AND ACTIONS OF ADRENOCORTICAL HORMONES... 

Breakdown of the long-lived proteins appears to be more or less non-selective but it is afrected by such factors as nutritional deprivation, hormones and inhibitors of protein synthesis and is effected by the various proteases present in the lysosomes. 

Appearance of new RNA fractions or increasing of RNA fractions which already existed in tissues that were treated with hormone. It should be mentioned that hormonal induction is inhibited by inhibitors of RNA synthesis (Wingaarden, 1970). 

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