Medical Physiology, 3rd Edition

Amine Hormones

Amine hormones are made from tyrosine and tryptophan

Four major amine hormones are recognized. The adrenal medulla makes the catecholamine hormones epinephrine and norepinephrine from the amino acid tyrosine (see Fig. 13-8C). These hormones are the principal active amine hormones made by the endocrine system. In addition to acting as a hormone, norepinephrine also serves as a neurotransmitter in the CNS (see p. 312) and in postganglionic sympathetic neurons (see pp. 342–343). Dopamine, which is also synthesized from tyrosine, acts as a neurotransmitter in the CNS (see p. 313); it is synthesized in other tissues, but its functional role outside the nervous system is not well clarified. Finally, the hormone serotonin is made from tryptophan (see Fig. 13-8B) by endocrine cells that are located within the gut mucosa. Serotonin appears to act locally to regulate both motor and secretory function in the gut, and also acts as a neurotransmitter in the CNS (see pp. 312–313).

The human adrenal medulla secretes principally epinephrine (see pp. 1030–1033). The final products are stored in vesicles called chromaffin granules. Secretion of catecholamines by the adrenal medulla appears to be mediated entirely by stimulation of the sympathetic division of the autonomic nervous system (see p. 343). Unlike the situation for many peptide hormones, in which the circulating concentration of the hormone (e.g., TSH) negatively feeds back on secretion of the releasing hormone (e.g., TRH), the amine hormones do not have such a hierarchic feedback system. Rather, the feedback of amine hormones is indirect. The higher control center does not sense circulating levels of the amine hormones (e.g., epinephrine) but rather a physiological end effect of that amine hormone (e.g., blood pressure; see pp. 534–536). The sensor of the end effect may be a peripheral receptor (e.g., stretch receptor) that communicates to the higher center (e.g., the CNS), and the efferent limb is the sympathetic outflow that determines release of the amine.

Serotonin (5-hydroxytryptamine, or 5-HT), in addition to being an important neurotransmitter in the CNS (see pp. 312–313 and Fig. 13-7B), is a hormone made by neuroendocrine cells, principally located within the lining of the small intestine and larger bronchi. Unlike the other hormones that we discuss in this chapter, serotonin is not made by a specific gland. Little is known about feedback regulation or even regulation of secretion of this hormone. Serotonin arouses considerable clinical interest because of the dramatic clinical presentation of patients with unusual tumors—called carcinoid tumors—of serotonin-secreting cells. Individuals with these tumors frequently present with carcinoid syndrome, characterized by episodes of spontaneous intense flushing in a typical pattern involving the head and neck and associated with diarrhea, bronchospasm, and occasionally right-sided valvular heart disease. The primary tumors involved can occur within the intestinal tract, in the bronchial tree, or more rarely at other sites.

Amine hormones act via surface receptors

Once secreted, circulating epinephrine is free to associate with specific adrenergic receptors, or adrenoceptors, located on the surface membranes of target cells. Numerous types of adrenoceptors exist and are generically grouped as α or β, each of which has several subtypes (see Table 14-2). Epinephrine has a greater affinity for β-adrenergic receptors than for α-adrenergic receptors, whereas norepinephrine acts predominantly through α-adrenergic receptors. All adrenoceptors that have been isolated from a variety of tissues and species are classic G protein–coupled receptors (GPCRs). β-adrenergic stimulation occurs through the adenylyl cyclase system. The α2 receptor also usually acts through adenylyl cyclase. However, α1-adrenergic stimulation is linked to Gαq, which activates a membrane-associated PLC that liberates IP3 and DAG. IP3 can release Ca2+ from intracellular stores, and DAG directly enhances the activity of PKC. Combined, these actions enhance the cellular activity of Ca2+-dependent kinases, which produce a metabolic response that is characteristic of the specific cell.

As indicated in Figure 47-5, the intracellular action of a specific catecholamine is determined by the complement of receptors present on the surface of a specific cell. For example, when epinephrine binds to the β1-adrenergic receptor, it activates a Gαs protein, which stimulates adenylyl cyclase, promotes increases in [cAMP]i, and thus enhances the activity of PKA (see Table 14-2). In contrast, when the same hormone binds to a cell displaying principally α2 receptors, it activates a Gαi protein, which inhibits adenylyl cyclase, diminishes [cAMP]i, and therefore reduces PKA activity. Thus, the response of a specific cell to adrenergic stimulation (whether via circulating epinephrine or via norepinephrine released locally by sympathetic neurons) depends on the receptor repertoire displayed by the cell. As a result, the response to adrenergic agonists varies among tissues; for example, glycogenolysis in the liver or muscle (predominantly a β effect), contraction (an α1 effect) or relaxation (a β2 effect) in vascular smooth muscle, or a change in the inotropic or chronotropic state of the heart (a β1 effect).


FIGURE 47-5 Catecholamine receptors. The β1, β2, and D1 receptors all interact with Gαs, which activates adenylyl cyclase (AC) and raises levels of cAMP. The α2 and D2 receptors interact with Gαi, which inhibits AC. Additionally, the α1 receptor interacts with Gαq, which activates PLC, which in turn converts phosphoinositides in the cell membrane to IP3 and DAG.

Dopamine also can interact with several GPCRs. The D1 receptor is coupled to Gαs and the D2 receptor is linked to Gαi.