Hormone action is mediated by receptors on or within their target cells

Water-soluble hormones cannot pass readily through cell membranes; instead they bind to receptors on the surfaces of target cells. These receptors are large transmembrane glycoprotein complexes with three domains:

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  1. A binding domain that projects outside the cell membrane

  2. A transmembrane domain that anchors the receptor in the membrane

  3. A cytoplasmic domain that extends into the cytoplasm of the cell

When a hormone binds to the binding domain, the cytoplasmic domain initiates the target cell’s response, usually through second messengers. Second messengers activate a cascade of intracellular events, eventually activating protein kinases or protein phosphatases (see Figures 7.6 and 7.7). In most cases these protein kinases and phosphatases activate or inactivate enzymes in the cytoplasm that lead to the cell’s response, but the signaling cascade initiated by the receptor can also generate signals that enter the nucleus and alter gene expression (see Figure 7.10).

Lipid-soluble hormones can diffuse through cell membranes, and therefore their receptors are usually inside cells, in either the cytoplasm or the nucleus. There are also some membrane-bound receptors for lipid-soluble hormones, but they are the exception rather than the rule. In most cases, the complex formed by the lipid-soluble hormone and its receptor acts by altering gene expression in the cell’s nucleus (see Figure 7.8).