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GENERAL CONCEPTS

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The classic concept that endocrine effects are the result of substances secreted into the blood with effects on a distant target cell has been updated to account for other ways in which hormonal effects occur. Specifically, some hormone systems involve the stimulation or inhibition of metabolic processes in neighboring cells (eg, within the pancreatic islets or cartilage). This phenomenon is termed paracrine. Other hormone effects reflect the action of hormones on the same cells that produced them. This action is termed autocrine. The discoveries of local production of insulin, glucagon, ghrelin, somatostatin, cholecystokinin, and many other hormones in the brain and gut support the concept of paracrine and autocrine processes in these tissues.

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Another significant discovery in endocrine physiology was an appreciation of the role of specific hormone receptors in target tissues, without which the hormonal effects cannot occur. For example, in the complete androgen insensitivity syndrome (AIS), androgen receptors are defective, and the 46,XY individual develops varying degrees of undervirilization of the external genitalia and internal (wolffian) duct system despite the presence of testes and adequate testosterone production. Similarly, in nephrogenic diabetes insipidus or Albright hereditary osteodystrophy (AHO) (pseudohypoparathyroidism [PHP]), affected children have defective antidiuretic hormone or parathyroid hormone (PTH) receptor function, respectively, and show the metabolic effects of diabetes insipidus or hypoparathyroidism despite more-than-adequate hormone secretion. Alternatively, abnormal activation of a hormone receptor leads to the effects of the hormone without its abnormal secretion. Examples of this phenomenon include McCune-Albright syndrome (precocious puberty and hyperthyroidism), testotoxicosis (familial male precocious puberty), and hypercalciuric hypocalcemia.

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HORMONE TYPES

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Hormones are of three main chemical types: peptides and proteins, steroids, and amines. The peptide hormones include the releasing factors secreted by the hypothalamus, the hormones of the anterior and posterior pituitary gland, pancreatic islet cells, parathyroid glands, lung (angiotensin II), heart and brain (atrial and brain natriuretic hormones), and local growth factors such as insulin-like growth factor 1 (IGF-1). Steroid hormones are secreted primarily by the adrenal cortex, gonads, and kidney (active vitamin D [1,25(OH)2 D3]). The amine hormones are secreted by the adrenal medulla (epinephrine) and the thyroid gland (triiodothyronine [T3] and thyroxine [T4]).

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As a rule, peptide hormones and epinephrine act after binding to specific receptors on the surface of their target cell. The metabolic effects of these hormones are usually stimulation or inhibition of the activity of preexisting enzymes or transport proteins (posttranslational effects). The steroid hormones, thyroid hormone, and active vitamin D, in contrast, act more slowly and bind to cytoplasmic receptors inside the target cell and subsequently to specific regions on nuclear DNA, where they direct a read-out of specific protein(s). Their metabolic effects are generally caused by stimulating or inhibiting the synthesis of new enzymes or transport proteins (transcriptional effects), thereby increasing or decreasing the amount rather than the activity of these proteins in the target cell.

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