Hormones function as a communication system within the body. The endocrine system, composed of various glands and the hormones they produce, interacts with essentially all other physiologic systems to regulate growth, metabolism, homeostasis, and reproduction. Because hormones circulate and act via receptors in target tissues, they serve to integrate physiologic responses to external or internal cues. For example, the light-dark cycle, sensed through the visual system, modulates hypothalamic corticotopin-releasing hormone (CRH), which increases pituitary adrenocorticotropin hormone (ACTH) production, leading to increased adrenal cortisol production before the time of waking in the morning. Increased cortisol, in turn, circulates throughout the body, acting via the nuclear glucocorticoid receptor, to activate numerous genetic programs that influence metabolism, the cardiovascular system, behavior, and the immune system. This chapter provides an overview of the different types of hormones and how they function at the cellular level to control myriad physiologic processes.
Hormones can be divided into five major types: (1) amino acid derivatives such as dopamine, catecholamine, and thyroid hormone; (2) small neuropeptides such as gonadotropin-releasing hormone (GnRH), thyrotropin-releasing hormone (TRH), somatostatin, and vasopressin; (3) large proteins such as insulin, luteinizing hormone (LH), and parathyroid hormone (PTH); (4) steroid hormones such as cortisol and estrogen that are synthesized from cholesterol-based precursors; and (5) vitamin derivatives such as retinoids (vitamin A) and vitamin D. A variety of peptide growth factors, most of which act locally, share actions with hormones. As a rule, amino acid derivatives and peptide hormones interact with cell-surface membrane receptors. Steroids, thyroid hormones, vitamin D, and retinoids are lipid-soluble and interact with intracellular nuclear receptors, although many also interact with membrane receptors or intracellular signaling proteins as well.
HORMONE AND RECEPTOR FAMILIES
Hormones and receptors can be grouped into families, reflecting structural similarities and evolutionary origins (Table 370-1). The evolution of these families generates diverse but highly selective pathways of hormone action. Recognition of these relationships has proven useful for extrapolating information gleaned from one hormone or receptor to other family members.
TABLE 370-1Examples of Membrane Receptor Families and Signaling Pathways ||Download (.pdf) TABLE 370-1 Examples of Membrane Receptor Families and Signaling Pathways
|RECEPTORS ||EFFECTORS ||SIGNALING PATHWAYS |
|G Protein–Coupled Seven-Transmembrane Receptor (GPCR) |
β-Adrenergic, LH, FSH, TSH
Glucagon, PTH, PTHrP, ACTH, MSH, GHRH, CRH
Gsα, adenylate cyclase
Stimulation of cyclic AMP production, protein kinase A
Calmodulin, Ca2+-dependent kinases
Inhibition of cyclic AMP production
Activation of K+, Ca2+ channels
Phospholipase C, diacyl-glycerol, IP3, protein kinase C, voltage-dependent Ca2+ channels
|Receptor Tyrosine Kinase |
Tyrosine kinases, IRS
Tyrosine kinases, ras
MAP kinases, PI 3-kinase; AKT
Raf, MAP kinases, RSK
|Cytokine Receptor–Linked Kinase |
|GH, PRL ||JAK, tyrosine kinases...|