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Introduction and MOA of steroidal hormones
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
transductionâso-called receptor-effector coupling âthat 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.
5.
6. Receptors Are Proteins
⢠The insulin receptor is a heterotetramer composed of two copies of two
different protein subunits ( ι2, 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.
8.
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
ďź Îą2 and β Adrenergic Catecholamines
ďźACTH
ďźADH
ďźCalcitonin
ďźFSH
ďźCRH
ďźLH
ďźPTH
ďźTSH
ďźSomatostatin
ďźGlucagon
11. ⢠The Second Messenger is c-GMP
ďANF
ďNO
⢠The second Messenger is Ca2+ or Phosphatidylinositol (or Both)
ďÎą1 Adrenergic catecholamines
ďCholecystokinin
ďGastrin
ďOxytocin
ďTRH
ďPDGF
ďAngiotensin-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
13.
14.
15.
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