Mechanism of hormone action

Hormone concentration in the blood is not fixed — it rises and falls according to the body's needs, and this is controlled by feedback mechanisms that act on the hypothalamus, the pituitary, or both, which in turn govern secretion of a particular downstream hormone. In positive feedback, hormone secretion increases further once triggered; in negative feedback (the far more common pattern in this chapter — thyroid, ACTH, PTH/TCT are all examples), rising hormone levels act back to slow further secretion. Feedback of this kind is the central mechanism that keeps the body in homeostasis.

Hormones fall into three chemical classes — peptide, steroid, and amino-acid-derived — and each class signals its target cell in a distinct way. Peptide hormones cannot cross the phospholipid cell membrane, so they bind receptors on the outside of the target cell, acting as a first messenger. Binding activates the membrane enzyme adenylate cyclase, which converts ATP into the intracellular second messenger cyclic AMP (cAMP); cAMP then regulates the cell's internal metabolic machinery (Figure 11.17). This two-step relay is called a signalling cascade, and it amplifies the original signal at every stage: one hormone molecule can bind and activate several receptor molecules before it is degraded, each activated receptor can switch on multiple adenylate cyclase enzymes, and each of those makes many cAMP molecules — so the effective signal grows larger at every step. The cascade is switched off by the enzyme phosphodiesterase, which breaks down cAMP; because the whole loop turns over quickly, peptide hormones like insulin, glucagon and somatotropin tend to have short-lived effects.

Steroid hormones, being lipid-soluble, cross the cell membrane freely and bind receptors located inside the cell — intracellular or intranuclear. Once bound, the hormone-receptor complex pairs up with a second such complex (dimerises), and this dimer binds directly to DNA, altering gene transcription (Figure 11.18). Because this changes the actual amount of mRNA and protein the cell makes, steroid hormone effects (such as those of aldosterone or oestrogen) tend to be much longer-lived than peptide hormone effects. …