13.3 Glucocorticoids and thyroid hormones
Glucagon and epinephrine act primarily on the activity of pre-formed enzymes.1 Insulin both affects pre-formed enzymes and induces the synthesis of new ones. Glucocorticoids and thyroid hormones mostly act by way of genetic regulation. Their receptors are not located at the cell surface but inside the cell. They are either found in the nucleus to begin with, or they translocate from the cytosol to the nucleus upon binding their ligand. The mechanism of this regulation is depicted in Figure 13.2-2 in simplified form. Binding of the hormone (H) to the receptor (R) causes the latter to recruit a bunch of other proteins (omitted) and together with these bind to specific target sequences in the DNA. This changes the expression levels of genes nearby. The proteins encoded by these genes will include enzymes of energy metabolism but also other hormone receptors; for example, cortisol and cortisone induce enzymes for glycogen metabolism and gluconeogenesis but also receptors for epinephrine. Major consequences are:
- Stimulation of protein breakdown. The amino acids released are largely used for gluconeogenesis.
- Increased enzyme activities for glycogen synthesis and breakdown (!), and for gluconeogenesis.
- Increased sensitivity to epinephrine and norepinephrine.
- Suppression of pain and inflammation by inhibition of prostaglandin synthesis.
Cortisol is often considered a chronical stress hormone, in contrast to the acute stress hormones epinephrine and norepinephrine.
Thyroid hormones also have a variety of regulatory targets. One key effect is the induction of thermogenin, which is simply an uncoupling protein. The mechanism by which uncoupling proteins increase metabolic spending has been described in section 6.1. The up-regulation of uncoupling proteins is responsible for the finding of accelerated metabolism, hyperthermia and weight loss in patients with excessive thyroid hormone secretion (hyperthyreosis).
1: protein kinase A affects transcriptional regulation as well, though.