Hormones and Signal Transduction Overview

Study Notes

Hormones and Signal Transduction

The nervous and endocrine systems are key body control systems. The nervous system uses electrochemical signals and the endocrine system relies on chemical mediators called hormones.
Hormones are chemical messengers synthesized in one cell type and transported via blood to act on other cells.
Hormones can be categorized based on their mechanism of action:
- Hormones with cell surface receptors
- Hormones with intracellular receptors

Cell Surface Receptors

Hormones with cell surface receptors utilize second messengers.
- cAMP (cyclic adenosine monophosphate):
  - ACTH, ADH, FSH, HCG, LH, TSH, MSH, PTH, CRH, Glucagon, Calcitonin, Catecholamine and Retinoic acid utilize cAMP as a second messenger.
  - The hormone receptor complex activates a G protein, which then activates adenylate cyclase.
  - Adenylate cyclase converts ATP to cAMP.
  - cAMP activates protein kinase A (PKA), which then phosphorylates target enzymes, leading to metabolic changes or gene expression.
- cGMP (cyclic guanosine monophosphate):
  - ANF (atrial natriuretic factor) and NO (nitric oxide) use cGMP as a second messenger.
  - cGMP activates protein kinase G (PKG), which phosphorylates proteins influencing cell function.
- Calcium:
  - TRH, GnRH, Catecholamines, Acetylcholine, CCK, Gastrin, Vasopressin, Oxytocin, and PDGF rely on calcium as a second messenger.
  - Calcium, often through calmodulin, activates enzymes such as adenylate cyclase, calcium-dependent protein kinases, and calcium-magnesium-ATPase.
- Tyrosine Kinase:
  - Insulin, Somatomedin, EGF, FGF, PDGF, CGSF, NGF, and IGF utilize tyrosine kinase pathways.
  - The hormone receptor complex directly activates tyrosine kinase, which in turn phosphorylates proteins involved in signaling and metabolism.
- Kinase or Phosphatase Cascade:
  - IL, GH, PRL, TNF, Adiponectin, Leptin, Resistin, and Erythropoietin utilize intracellular kinase or phosphatase pathways.
  - The receptor triggers a series of phosphorylation and dephosphorylation events, altering protein activity and cellular responses.

Intracellular Receptors

Steroid and thyroid hormones interact with intracellular receptors.
- Hormones diffuse through the plasma membrane and bind to receptors in the cytoplasm.
- The hormone-receptor complex translocates to the nucleus.
- Within the nucleus, the complex binds to hormone response elements (HRE) or steroid response elements (SRE).
- HREs/SREs are located on DNA and act as enhancer elements, increasing gene transcription.
- New mRNA is synthesized and translated into proteins, mediating the hormone's biological effects.
Examples:
- Glucocorticoids induce aminotransferase synthesis.
- Calcitriol (active vitamin D) promotes synthesis of calcium binding proteins.