Small-Molecule Hormones: Molecular Mechanisms of Action
Figure 6
Simplified diagram of nongenomic mechanisms of action of small-molecule hormones. All nongenomic mechanisms activate numerous transduction pathways, and, by a series of phosphorylation events of cytoplasmic and of nuclear proteins, modify cell function. (A) Interaction of the hormone with either cell membrane receptor or directly with membrane phospholipids modifies the function of ion channels. (B) Activation of phospholipase (C) initiated by the hormone-activated cell membrane receptor, and of adenylate cyclase (and, most possibly, of other enzymes) stimulates production of secondary messengers. (C) Activation of c-SRC by the hormone-activated nuclear receptor. (D) The binding of the hormone-activated nuclear receptor to the phosphatidylinositol 3 kinase p85 subunit activates this enzyme and results in an increased synthesis of inositol triphosphate. (E) In mitochondria, small-molecule hormones acting via their nuclear receptors or by their shorter (mitochondrial) isoforms regulate transcription of mitochondrial DNA. In addition, interaction of some hormones alone or of hormone-receptor complexes with mitochondrial proteins stimulates thermogenesis. (F) The binding of the hormone activates protein kinase. (C) HR: various types of hormone receptors, Ca2+: calcium ion, p85, p110: phosphatidylinositol 3 kinase subunits, PI3K: phosphatidylinositol 3 kinase, IP3: inositol triphosphate, PLC: phospholipase. (C) AC: adenylate cyclase, cAMP: cyclic AMP, AKT: protein kinase. (B) c-SRC: tyrosine kinase, PKA: protein kinase. (A) PKC: protein kinase. (C) MAPK: mitogen-activated protein kinase, RAS/MEK/ERK: protein kinases, p28: shortest isoform of TR, mtDNA: mitochondrial DNA, HRE: hormone response element, TF: transcription factor, BTF: basal transcription factors, and RNA Pol II: type II RNA polymerase.
