After studying this chapter, you should be able to:
Describe hormones and their contribution to whole body homeostasis.
Understand the chemical nature of different classes of hormones and how this determines their mechanism of action.
Define how hormones are synthesized and secreted.
Explain the relevance of protein carriers in the blood for hydrophobic hormones, and the mechanisms that determine the level of free circulating hormones.
Understand the principles of feedback control for hormone release and its relevance for homeostasis.
Understand disease states that result from over- or underproduction of key hormones.
This section of the text deals with the various endocrine glands that control the function of multiple organ systems of the body. In general, endocrine physiology is concerned with the maintenance of homeostasis. The mediators of such control mechanisms are soluble factors known as hormones. In preparation for specific discussions of the various endocrine systems and their hormones, this chapter addresses common concepts of endocrine regulation.
EVOLUTION OF HORMONES & THEIR ACTIONS ON TARGET CELLS
Many hormones can be grouped into families reflecting their structural similarities as well as the similarities of the receptors they activate. The number of hormones and their diversity increases as one moves from simple to higher life forms. This molecular evolution implies that hormone receptors also needed to evolve to allow for spreading of hormone actions/specificity. This was accomplished by coevolution of the G-protein–coupled receptors (GPCR) and receptor tyrosine kinases that mediate the effects of peptide and amine hormones that act at the cell surface (see Chapter 2).
Steroids and thyroid hormones are distinguished by their predominantly intracellular sites of action, since they can diffuse freely through the cell membrane. They bind to a family of largely cytoplasmic proteins known as nuclear receptors. Upon ligand binding, the receptor–ligand complex translocates to the nucleus. The complex binds to DNA to either increase or decrease gene transcription in the target tissue. Individual members of the nuclear receptor family have a considerable degree of homology and share many functional domains, such as the zinc fingers that permit DNA binding. However, sequence variations allow for ligand specificity as well as binding to specific DNA motifs. In this way, the transcription of distinct genes is regulated by individual hormones.
For peptide hormones as well as hormone receptors, synthesis is controlled predominantly at the level of transcription. For amine and steroid hormones, synthesis is controlled indirectly by regulating the production of key synthetic enzymes as well as by substrate availability.
The majority of peptide hormones are synthesized initially as much larger polypeptide chains, and then processed intracellularly by specific proteases to yield the final hormone molecule. The hormone precursors themselves are typically inactive. This may provide for an additional measure of ...