EXAM 3: BIO&252 (Chapter 18: Part 1)

• Protein/glycoprotein
• Located in cell membrane or within cytoplasm, nucleus, or mitochondrion
• Target = cell with specific receptors/hormones
• No recpetor, no effect on hormone

1. Cause synthesis of new proteins (ex. make new enzymes

2. Modify transcription/translation rate of existing proteins (make more/less)

3. Modify activity/function of existing enzymes (increase/decrease enzyme activity)

• 1. Ciruclating Hormones: "endocrines = "typical hormone" (most abundant)
•    *Transported in blood; affect target cells all over the body

• 2. Paracrine Hormones: act only on nearby cells (do not go through the body)
•    *E.g. somatostatin from delta cells in pancreatic islets inhibits secretion of insulin by beta cells

• 3. Autocrine Hormones: Act on cell that secretes it
•    *E.g. Helper T cells release interleukin 2 which stimulates the proliferation of cell that secretes it

• A. Derivatives of tyrosine
•    *Catecholamines (Epi and Norepi)
•    *Thyroid Hormones (T₃ and T₄ thyroxine)

• B. Derivative of tryptophan
•    *Melatonin from pineal

• Usually produced as prohormones
• Prohormone = enzyme = active hormone

• A. All hypothalamic hormones (releasing hormones, and ADH and OT)
• B. All anterior pituitary hormones
• C. All pancreatic hormones
• D. Calcium-regulating hormones (PTH, Calcitonin)
• E. Digestive hormones
• F. Erythropoietin (kidneys)

• A. Derivatives of cholesterol = steroid hormones
•    *From gonads (androgens, estrogens, progestins)
•    *From adrenal cortex (mineralcorticoids [aldosterone], glucocorticoids [cortisol], gonadocorticoids [androgens])
•    *From kidneys (calcitrol [Vit D])

• B. Derivatives of arachadonic acid
•    *Eicosanoids
•       Prostoglandins (many tissues)
•       Leukotrienes (white blood cells)

• Hormone NOT bound to carrier molecule
• E.g. Catecholamines, peptides, proteins

• Transport requires a carrier molecule (e.g. steroids, thyroid hormones)
• Functions of the carrier
•    a. Increases solubility in plasma and ECF
•    b. Decreases hormone loss at kidney
•    c. Forms a hormone reserve

• Hormone reserve
• *Equilibrium exists between "bound" and "free" form
• *Free fraction usually a very small % of total
• *More of the bound form is released as free form is used up.

• Bind to receptors (some inside of cells)
• Broken down by enzymes in liver, kidneys
• Broken down by enzymes in plasma or ECF

• Depend upon lipid vs. water solubility
•    a. Water-soluble hormone: act on membrane receptors
•    b. Lipid-soluble hormone: act intracelluarly

• First Messenger (hormone)
• Bind to receptor (usually a G-protein)

• Second Messenger
• E.g. cAMP, cGMP, Ca2+
• Functions:
•    *Enzyme activator
•    *Enzyme inhibitor
•    *Enzyme cofactor (facilitates function)

• Mechanism of action
• Many 2nd messengers of the same type are formed

• Mechanism of action
• Different 2nd messengers activated, sequence of biochemical reactions

• Downregulation
• Hormone levels high
• Number of receptors and sensitivity to hormones went DOWN

• Upregulation
• Hormone levels low
• Opposite effects

• G Proteins and cAMP
•    *Hormone binds receptor, G protein activated
•       a. Activate adenylate cyclase, which will INCREASE cAMP, or...
•       b. Activate PDE, which will LOWER cAMP

• cAMP (2nd messenger) activates kinases
• Kinases phosphorylate proteins which...
•    *Open membrane channels and alter enzyme acitivity
• (PDE inactivates cAMP)

• E.g. Hormones
• β receptors for E and NE
• PTH and calcitonin ([Ca²⁺])
• FSH and LH (ovaries and testis)

• E.g. Disease = Cholera - altered G protein function
• Toxin activates G proteins
• G proteins can't be turned off
• Causes increased cAMP levels in gut
• Increased pumping of Cl- out of cells
• Na⁺ and water follow = diarrhea, dehydration, death

• E.g. E and NE at α2 recpetors
• G protein activates PDE; adenylate cyclase is not activated
•    *PDE breaks down cAMP to AMP causing: 
•       -Decrease cAMP
•       -Decrease of kinase activation
•       -Decrease enzyme activity

• Hormone must be lipid soluble
•    *Binds receptors in cytoplasm
•    *Hormone receptor complex enters nucleus
•    *Alters gene expression

• E.g. testosterone
• Binds receptor in cytoplasm
• Hormone receptor complex enters nucleus
• Alters gene expression

INTRACELLULAR HORMONE RECEPTORS

• E.g. thyroid hormone
•       a. binds receptors on mitochondria
•          *increase ATP production and use(NA/K pump)
•       b. Bind receptors in nucleus
•            * Alters gene expression

• 1. Humoral stimuli (concentration in CSF)
•   e.g. parathyroid gland
•        .↓ [CA²] in CSF → release PTH
• 2. Hormonal Stimuli (Tropic hormones)
•   e.g. adrenal cortex
•        . Release cortisol in respond to ACTH
• 3. Neural Stimuli (action potential)
•   e.g. posterior pituitary 
•        . Action potentials cause ADH and OT release