23. General Principles of Endocrine Physiology
The endocrine and nervous systems are the major control systems of the body. The endocrine system regulates functions by releasing hormones, whereas the nervous system regulates functions by releasing neurotransmitters. There is some overlap between hormones and neurotransmitters; for example, epinephrine acts as both.
Protein and Peptide Hormone Synthesis
Protein and peptide hormones are synthesized in the endoplasmic reticulum, where they are assembled into chains of amino acid residues and then folded.
– These hormones are hydrophilic and most bind to plasma proteins in the blood. They require membrane receptors to act on cells.
Tyrosine-derived Hormone Synthesis
Tyrosine-derived hormones include norepinephrine, epinephrine, dopamine, and the thyroid hormones triiodothyronine (T3) and thyroxine (T4).
– Norepinephrine and dopamine are synthesized in nerve terminals. Epinephrine (and some norepinephrine) is synthesized in the adrenal medulla (see pages 276–277). These hormones are hydrophilic and act on membrane receptors.
– Thyroid hormones are synthesized in thyroid follicular cells (see pages 251–254). They are lipophilic and so can diffuse into cells and act on cytoplasmic or nuclear receptors.
Steroid Hormone Synthesis
Steroid hormones are synthesized from cholesterol in the adrenal cortex, testes, and ovaries (see page 270).
– Steroid hormones are lipophilic and therefore diffuse into cells and act on cytoplasmic receptors.
– Eicosanoids are derived from fatty acids, mainly arachidonic acid. They interact with cell membrane receptors.
Table 23.1 provides examples of each of the hormone types discussed.
Eicosanoids (eicosa = Greek for 20) are a group of autocoids (biological factors synthesized and released locally that play a role in vasoconstriction, vasodilation, and/or inflammation) that are derived from the 20-carbon cell membrane fatty acid arachidonic acid. Arachidonic acid forms arachidonate when acted upon by phospholipase A2. Phospholipase A2 is activated by hormones or other stimuli and is inactivated by steroids. Arachidonate is then further metabolized by cyclooxygenases (COX-1, COX-2, and COX-3) to form prostaglandin H2. PGH2 is the parent substance for prostacyclins, prostaglandins, and thromboxanes. In a different pathway, PGH2 may be acted upon by lipooxygenase, forming hydroand hydroperoxy fatty acids, which then form leukotrienes. Acetylsalicylic acid and related nonsteroidal antiinflammatory drugs (NSAIDs) inhibit the cyclooxygenases, thereby blocking the formation of most eicosanoids. These drugs have analgesic, antipyretic, and antirheumatic effects.
Catecholamines, peptides, and small proteins generally circulate in free form.
Steroid hormones, and thyroid hormones, and some protein hormones are bound to transport proteins. There are nonselective transporters (e.g., albumin and prealbumin) and specific transporters (e.g., thyroxine-binding globulin [TBG] and corticosteroid-binding globulin [CBG]). These are produced in the liver. The function of the transporters is to keep hormones in an inactive state until the target is reached, to act as a reservoir, to prevent small hormone molecules from passing into the urine, to slow the actions of the liver to transform a hormone into an inactive form, and to regulate a hormone’s half-life.
Hormone release may be initiated by neuronal stimulation, by the action of releasing hormones, or as a direct response to fluctuating plasma levels. Table 23.2 provides examples of hormones released by these mechanisms.
The release of hormones is tightly regulated because very low levels of hormones in the blood can act quickly and have powerful effects on the body. Regulation of secretion occurs by feedback control. Regulation of the duration and magnitude of response occurs via the rate of degradation in the bloodstream (half-life) and upregulation or downregulation of receptors.
Half-life of hormones
The half-life of any substance in the blood stream is the duration of time until its concentration decreases by one-half of its orig inal concentration. Steroid hormones are largely bound to plasma proteins, so they have a half-life of 1 or 2 hours. Thyroxine is bound and has the longest half-life of 5 to 7 days. Catecholamines have the shortest half-life of < 1 minute.
Negative feedback. Negative feedback occurs when hormones feedback at any preceding point in the cascade to directly or indirectly inhibit its own secretion or that of another hormone.
– This is the most common mechanism of hormonal regulation and is a self-limiting process.
Note: In pathological hormone derangement, negative feedback can steer hormone production toward normal, but is generally ineffective in overcoming the original defect.
Positive feedback. Positive feedback is when a hormone directly or indirectly stimulates its own secretion or that of another hormone. This system is designed to be self-perpetuating and to increase the magnitude of the response in target tissues.
– In hormonal terms, this is a rare form of regulation.
Regulation of Receptors
Upregulation of receptors. Upregulation of receptors is an increase in the number of receptors or their affinity for a hormone.
Downregulation of receptors. Downregulation of receptors is a decrease in the number of receptors or their binding affinity for a hormone.
– This occurs if hormone secretion is abnormally high for an extended period.
Table 23.3 provides examples of each of the mechanisms of hormonal regulation.
Hormones interact with receptors on the cell membrane, cytoplasm, or nucleus. The number of available receptors and the binding affinity between receptor and hormone are important for a hormonal effect. See pages 7 to 10 for a discussion of receptors and the mechanisms of signal transduction. Table 23.4 lists the mechanisms of signal transduction of hormones.