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 400e-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 400e-1Examples of Membrane Receptor Families and Signaling Pathways ||Download (.pdf) TABLE 400e-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 ||STAT, MAP kinase, PI 3-kinase, IRS-1 |
|Serine Kinase |
|Activin, TGF-β, MIS ||Serine kinase ||Smads |
The glycoprotein hormone family, consisting of thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), LH, and human chorionic gonadotropin (hCG), illustrates many features of related hormones. The glycoprotein hormones are heterodimers that share the α subunit in common; the β subunits are distinct and confer specific biologic actions. The overall three-dimensional architecture of the β subunits is similar, reflecting the locations of conserved disulfide bonds that restrain protein conformation. The cloning of the β-subunit genes from multiple species suggests that this family arose from a common ancestral ...