Steroid messenger regulation

ANSWERS TO CASE 7 HYPERTHYROIDISM/STEROID MESSENGER REGULATION OF TRANSLATION... 

In humans, most steroids function as hormones, chemical messengers that are secreted by endocrine glands and carried through the bloodstream to target tissues. There are two main classes of steroid hormones the sex hormones, which control maturation, tissue growth, and reproduction, and the adrenocortical hormones, which regulate a variety of metabolic processes. 

The cellular mechanism of action of hydrocortisone, a glucocorticoid, is also related to proteins but not by the enhancement of cAMP production. Hydrocortisone is transported by simple diffusion across the membrane of the cell into the cytoplasm and binds to a specific receptor The steroid-receptor complex is activated and enters the nucleus, where it regulates transcription of specific gene sequences into ribonucleic acid (RNA). Eventually, messenger RNA (mRNA) is translated to form specific proteins in the cytoplasm that are involved in the steroid-induced cellular response. 

Hormonal actions on target neurons are classified in terms of cellular mechanisms of action. Hormones act either via cell-surface or intracellular receptors. Peptide hormones and amino-acid derivatives, such as epinephrine, act on cell-surface receptors that do such things as open ion-channels, cause rapid electrical responses and facilitate exocytosis of hormones or neurotransmitters. Alternatively, they activate second-messenger systems at the cell membrane, such as those involving cAMP, Ca2+/ calmodulin or phosphoinositides (see Chs 20 and 24), which leads to phosphorylation of proteins inside various parts of the target cell (Fig. 52-2A). Steroid hormones and thyroid hormone, on the other hand, act on intracellular receptors in cell nuclei to regulate gene expression and protein synthesis (Fig. 52-2B). Steroid hormones can also affect cell-surface events via receptors at or near the cell surface. 

Receptor-effector mechanisms include (1) enzymes with catalytic activities, (2) ion channels that gate the transmembrane flux of ions (ionotropic receptors), (3) G protein-coupled receptors that activate intracellular messengers (metabotropic receptors), and (4) cytosolic receptors that regulate gene transcription. Cytosolic receptors are a specific mechanism of many steroid and thyroid hormones. The ionotropic and metabotropic receptors are discussed in relevance to specific neurotransmitters in chapter 2. 

All corticosteroids have the same general mechanism of action they traverse cell membranes and bind to a specific cytoplasmic receptor. The steroid-receptor complex translocates to the cell nucleus, where it attaches to nuclear binding sites and initiates synthesis of messenger ribonucleic acid (mRNA). The novel proteins that are formed may exert a variety of effects on cellular functions. The precise mechanisms whereby the corticosteroids exert their therapeutic benefit in asthma remain unclear, although the benefit is likely to be due to several actions rather than one specific action and is related to their ability to inhibit inflammatory processes. At the molecular level, corticosteroids regulate the transcription of a number of genes, including those for several cytokines. 

Acting as an intracellular second messenger, cAMP mediates such hormonal responses as the mobilization of stored energy (the breakdown of carbohydrates in liver or triglycerides in fat cells stimulated by B-adrenomimetic catecholamines), conservation of water by the kidney (mediated by vasopressin), Ca2+ homeostasis (regulated by parathyroid hormone), and increased rate and contractile force of heart muscle ( -adrenomimetic catecholamines). It also regulates the production of adrenal and sex steroids (in response to corticotropin or follicle-stimulating hormone), relaxation of smooth muscle, and many other endocrine and neural processes. 

Steroid Hormones. Generally, steroid hormones arc mctaholically short-lived steroids produced in small amounts by various endocrine glands. They serve as chemical messengers that regulate a variety of physiological and metabolic activities in vertehrates. Steroid hormones bind to soluble, intracellular receptor molecules. In the nucleus of... 

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