1. Introduction and MOA of
Steroidal Hormones
Dr. Abhishek Roy
Junior Resident (2nd Year),
Dept. of Biochemistry,
Grant Medical College &
Sir J.J. Group of Hospitals, Mumbai
Email: mail@abhishek.ro
Date: 02/07/2014

2. Determinants of the Concentration of a
Hormone at the Target Cell
• The rate of synthesis and secretion of the hormones.
• The proximity of the target cell to the hormone source (dilution
effect).
• The dissociation constants of the hormone with specific plasma
transport proteins (if any).
• The conversion of inactive or sub-optimally active forms of the
hormone into the fully active form.
• The rate of clearance from plasma by other tissues or by digestion,
metabolism, or excretion.

3. Determinants of the Target Cell Response
• The number, relative activity, and state of occupancy of the specific
receptors on the plasma membrane or in the cytoplasm or nucleus.
• The metabolism (activation or inactivation) of the hormone in the target
cell.
• The presence of other factors within the cell that are necessary for the
hormone response.
• Up- or down-regulation of the receptor consequent to the interaction
with the ligand.
• Post-receptor de-sensitzation of the cell, including down-regulation of
the receptor.

4. Both Recognition & Coupling Domains Occur
on Receptors
• The domains responsible for hormone recognition and signal
generation have been identified in the protein polypeptide and
catecholamine hormone receptors.
• The dual functions of binding and coupling ultimately define a
receptor, and it is the coupling of hormone binding to signal
transduction—so-called receptor-effector coupling —that provides the
first step in amplification of the hormonal response.
• This dual purpose also distinguishes the target cell receptor from the
plasma carrier proteins that bind hormone but do not generate a
signal.

6. Receptors Are Proteins
• The insulin receptor is a heterotetramer composed of two copies of two
different protein subunits ( α2, β2 ) linked by multiple disulfide bonds in
which the extracellular subunit binds insulin and the membrane-
spanning subunit transduces the signal through the tyrosine protein
kinase domain located in the cytoplasmic portion of this polypeptide.
• The receptors for insulin-like growth factor I (IGF-I) and epidermal growth
factor (EGF) are generally similar in structure to the insulin receptor.
• A comparison of several different steroid receptors with thyroid hormone
receptors revealed a remarkable conservation of the amino acid
sequence in certain regions, particularly in the DNA-binding domains.

7. General features of Hormone Classes
Group I
• Types Steroids, Iodothyronines,
Calcitriols, retinoids
• Solubility Lipophilic
• Transport proteins Yes
• Plasma half-life Long(Hours to days)
• Receptor Intracellular
• Mediator Receptor-Hormone Complex
Group II
Polypeptides,Glycoproteins
Catecholamines, Proteins
Hydrophilic
No
Short (Minutes)
Plasma Membrane
cAMP, cGMP, Ca2+ etc.

9. Hormones that bind to intracellular receptors
• Calcitriol
• Glucocorticoids
• Mineralocorticoids
• Progestins
• Retinoic Acids
• Thyroid Hormones (T3 and T4)

10. Hormones that bind to cell surface receptors
• Second messenger is c-AMP
 α2 and β Adrenergic Catecholamines
ACTH
ADH
Calcitonin
FSH
CRH
LH
PTH
TSH
Somatostatin
Glucagon

11. • The Second Messenger is c-GMP
ANF
NO
• The second Messenger is Ca2+ or Phosphatidylinositol (or Both)
α1 Adrenergic catecholamines
Cholecystokinin
Gastrin
Oxytocin
TRH
PDGF
Angiotensin-II

12. • The second messenger is a kinase or phosphatase cascade
• Adiponectin
• Chorionic somato-mammotropin
• Epidermal growth factor
• Erythropoietin
• Fibroblast growth factor (FGF)
• Growth hormone (GH)
• Insulin
• Insulin-like growth factors I and II
• Leptin
• Nerve growth factor (NGF)
• Platelet-derived growth factor
• Prolactin

16. The DNA Sequences of Several Hormone Response Elements (HREs)
• Glucocorticoids GRE GGTACA NNN TGTTCT
• Progestins PRE
• Mineralocorticoids MRE
• Androgens ARE
• Estrogens ERE AGGTCA NNN TGA/TCCT
• Thyroid hormone TRE
• Retinoic acid RARE AGGTCA N3,4,5 AGGTCA
• Vitamin D VDRE
• cAMP CRE TGACGTCA