Porth's Essentials of Pathophysiology, 4e

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Mechanisms of Endocrine Control

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mediated. These hormones are synthesized in the rough endoplasmic reticulum of the endocrine cell in a manner similar to the synthesis of other proteins (see Chapter 1). The appropriate amino acid sequence is dictated by messenger ribonucleic acids (mRNAs) from the nucleus. Usually, synthesis involves the production of a precursor hormone, which is modified by the addition of peptides or sugar units. These precursor hormones often con- tain extra peptide units that ensure proper folding of the molecule and insertion of essential linkages. If extra amino acids are present, as in insulin, the precursor hor- mone is called a prohormone. After synthesis and sequestration in the endoplasmic reticulum, the protein and peptide hormones move into the Golgi complex, where they are packaged in vesicles. It is in the Golgi complex that prohormones are con- verted into hormones. Stimulation of the endocrine cell causes the vesicles to move to the cell membrane and release their hormones. The vesicle-mediated pathway is also used for secretion of a number of nonpolypeptide hormones and neurotransmitters such as the catecholamines (epineph- rine and norepinephrine). However, these small mole- cules do not pass through the full range of intracellular mechanisms seen in the synthesis and secretion of the larger protein and polypeptide hormones. Non–Vesicle-Mediated Synthesis. Hormones syn- thesized by non–vesicle-mediated pathways include the glucocorticoids, androgens, estrogens, and mineralo- corticoids—all steroids derived from cholesterol. These hormones are synthesized in the smooth endoplasmic reticulum, and steroid-secreting cells can be identified by their large amounts of smooth endoplasmic reticu- lum. Certain steroids serve as precursors for the pro- duction of other hormones. In the adrenal cortex, for example, progesterone and other steroid intermediates are enzymatically converted into aldosterone, cortisol, or androgens (see Chapter 32). The release of hormones synthesized by non–vesicle- mediated pathways is not fully understood. Historically it was thought to occur by simple diffusion. In recent years, however, specific transporters have been impli- cated in directing some of these classes of hormones out of the cell. Whether all hormones produced by non–vesicle-mediated pathways depend on transport- ers for their secretion remains a subject for further investigation. HormoneTransport and Clearance from the Blood The signaling of the endocrine system relies on mecha- nisms that transport blood-borne chemical messengers to the site of action, and then clear them from the blood once their action is no longer needed. Transport Mechanisms. Hormones that are released into the bloodstream circulate as either free or unbound molecules or as hormones attached to transport carri- ers (Fig. 31-3). Peptide hormones and protein hormones

Endocrine gland (thyroid)

Circulation

Hormone

A

Distant target cell

Paracrine

B

Paracrine cell

Nearby target cell

Autocrine

C

Autocrine cell

FIGURE 31-2. Examples of endocrine (A) , paracrine (B) , and autocrine (C) secretions.

circulation, and are thought to act mainly by paracrine and autocrine mechanisms. Eicosanoid synthesis often is stimulated in response to hormones, and they serve as mediators of hormone action. An extension of the endocrine system is represented by numerous cell types with enzymes that modify inac- tive precursors or less active hormones into highly active hormones. An example is the conversion of the inactive circulating plasma protein angiotensinogen to highly active angiotensin II by the enzymatic action of renin, which is produced by the kidney, and angiotensin-con- verting enzyme, which is present in the lung (see Chapter 18, Fig. 18-13). Another example is the activation of vitamin D by two subsequent hydroxylation reactions in the liver and kidney to produce the highly bioactive form of vitamin D. Hormone Synthesis The mechanisms for hormone synthesis and release vary with hormone structure. Protein and polypeptide hormones are synthesized and stored in vesicles in the cytoplasm of the cell until secretion is required. Other hormones, such as the lipid-soluble steroid hormones, are released as they are synthesized. Vesicle-Mediated Synthesis. The protein and poly- peptide hormones comprise the most prominent class of hormones whose synthesis and release is vesicle