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Transcript
Endocrine Physiology 1
Chapter 11
Chapter Outline
Hormones and precursors (prohormones and prehormones)
Chemical classes: amines, peptides, glycoproteins and steroids
Hormonal interactions: permissive, synergistic and antagonistic
Hormone concentration: abnormal high concentrations and desensitized target cells
Mechanisms of hormonal actions: Lipophilic and polar hormones
Pituitary gland: tropic/trophic hormones and
Hypothalamus: releasing / inhibiting hormones
Adrenal Glands
Thyroid and Parathyroid glands
Pancreas and other endocrine glands: pineal, gastrointestinal tract, gonads, and placenta
Autocrine and Paracrine regulation: somatomedins, Nitric oxide, neutrophins, interleukins, and
prostglandins
Hormones, Prohormones and Prehormones
Hormones: The endocrine system uses chemical messengers called hormones always secreted by
ductless glands = endocrine into surrounding extracellular fluids and reach blood from there. Blood
carries hormones to non-adjacent cells called target cells. Target cells have specific receptors for
particular hormones and undergo changes when hormone binds to the receptor.
Prohormones are formed inside ER by cleaving bigger proteins formed by ribosomes  active
hormones inside golgi apparatus
Prehormones are released by endocrine gland and modified by another organ to active hormone
Chemical classes of hormones
Polar or Hydrophilic hormones transport dissolved in water in plasma of blood.
Amines: epinephrine, norepinephrine
Peptides/polypeptides: ADH and Oxytocin = 8 amino acids; insulin = 21 and 30 amino acids in 2
chains, glucagon = 29 amino acids, ACTH = 39 amino acids, PTH = 84 amino acids
Glycoproteins = FSH, LH, TSH
Lipophilic Hormones: cannot dissolve in water and attach to transport proteins in plasma.
Thyroid hormones:
Steroid hormones:
Lipophilic Hormones
Lipid soluble
Receptors inside cytosol or nucleus
Act by modifying gene- expression
Examples include steroid and thyroid hormones
Signal Transduction Pathway - lipid-soluble messenger
Messenger passes the cell membrane and binds to the receptor mostly in nucleus, sometimes in
cytosol. Activated receptor acts as a Transcription Factor.
Activated-receptor binds to a specific sequence = Response Element near a gene.
This binding alters the rate of transcription of that gene. It means if already active it can slow down
or stop the transcription. On the contrary, if not going on, it can turn on the transcription or speed it
up.
If transcription is turned on m-RNA goes out in the cytosol and produces a new protein which can
act as an enzyme or receptor or a channel or a secretory protein and so on.
This shows up as cellular changes.
Hydrophilic Hormones
Peptide/protein and catecholamine hormones
4 kinds of Receptors for water soluble messengers. Water soluble messengers are polar substances
and cannot enter the cell membrane. Therefore their receptors are present on the cell membrane.
4 kinds of receptors are:
A ligand gated Channel – Na+ channel in postsynaptic membrane
Receptor is an enzyme – Tyrosine kinase – insulin hormone and glucose absorption
(Activate cytosolic JAK kinase)
Interact with plasma membrane bound G-protein. G-protein complex has α, β, and γ units.
Hormone attaches to G-protein and releases α of 3 units and activate membrane bound enzyme
(adenylate cyclase) to change into ATP  cAMP (2nd messenger).
The phospholipase C-Ca2+ second messenger system:
Role of Epinephrine
Epinephrine has α and β adrenergic receptors. Epinephrine uses two 2nd messengers cAMP and
calmodulin. Binding to β-adrenergic receptor activates enzyme adenylase cyclase. It converts ATP
to cAMP. cAMP activates Protein Kinase. Binding of epinphrine to α-adrenergic receptor opens
Ca2+ channel which attaches to Calmodulin and activates Protein kinase. Active Protein Kinase
initiates breakdown of Glycogen to cause release of glucose from liver cell.
Action of Insulin:
Tyrosine Kinase is a membrane bound enzyme for Insulin. Insulin attaches to tyrosine kinase leading
to its phosphorylation. Activated enzyme now uses ATP to phosphorylation of signal molecules.
Cascade of effects causes up-regulation of transport proteins for glucose. It leads to uptake of
glucose and anabolism. Fig 6.17
Role of Vitamin D3:
1, 25-dihydroxyvitamin D3 is active form of Vitamin D3.
Skin produces a prehormone Vitamin D3 by using UV rays of sunlight. An enzyme in liver adds a
hydroxyl group at carbon 25. Another enzyme in kidney, adds 2nd hydroxyl group at carbon 1 to
produce active hormone 1, 25-dihydroxyvitamin D3.
7-dyhdrocholesterol  vitamin D3  25-hydroxy vitamin D3  1, 25-dihydroxyvitamin D3
Effects of 1, 25-dihydroxyvitamin D3
increases absorption of Ca2+ and PO4-3 by intestine.
Promotes formation of hydroxyapatite crystals in bone
Promotes formation of osteoclasts and bone resorption when Ca2+ is low.