basic concepts

Question 1

There are 2 big classes of hormones

Answer 1

Group 1: the slow acting ones: Steroids/iodothyronines, lipophiliic, use transport proteins, have long half lives, intracellular receptors, receptor-hormone complex mediator

Group 2: the fast acting ones: polypeptides, proteins, glycoproteins, catecholamines, hydrophilic, dont really use transport proteins, short half life, plasma membrane receptors, mediators: cAMP, cGMP, Ca++, metabolites of complex phosphinoositols, kinase cascade

Question 2

Pearls of hormones

Answer 2

Steroids all synthesized from some form of cholesterol
Thyroid hormones contain iodine (T4- has 4, T3 has 3)
Peptides generally do not have tertiatry structure whereas proteins do
Glycoproteins (LH, FSH, TSH, hCG) all have same alpha subunit- specificity is in the beta subunit- pregnancy subunit is hCG

Question 3

Bound vs free hormones

Answer 3

1. thyroid hormones are bound >99.5% to TBG, transthyretin, and albumin- Therefore, their plasma half life is very long (T4 is 6 days), and metabolic clearance is very slow
2. Steroid hormones are bound 90-98% to plasma proteins (eg cortisol to CBG, testosterone to SHBG)- their half-life (30-60 mins) shorter than thyroid hormones but still longer than most peptides and proteins
3. Most peptides and proteins circulate only in the free form (unbound), so their half lives are very short (<15 min) and their clearance rate is high (some exceptions)

Question 4

Steroidogenesis

Answer 4

All start from cholesterol
Lipid, transported via StAR (steroidogenic acute regulatory protein), StAR takes the cholesterol and injects it into the mitochondria where the first step is P450 scc (Side chain cleavage)- StAR transport is the RATE LIMITING STEP

RLS of steroidogenisis is StAR protein mediation of cholesterol uptake from the cytosol to the inner mitochondrial membrane where P450 scc is located
Expression of the different ezymes determine the major steroid product of each gland
Gprotein couple receptor expression on the cell membrane determines which circulating secretagogue the gland will respond to (ACTH, Ang 2, FSH, and LH)

Question 5

chemistry of hormones, pearls

Answer 5

The chemical nature of a hormone or a drug determines its MOA
The expression of the appropriate receptor in tissue determines which hormones will act on that tissue (specificity of hormone action)
Thyroid hormones act via nuclear receptors to increase transcription and translation (slow)
Steroid hormones act via cytoplasmic (eg cortisol) or nuclear (estrogen) receptors to increase transcription and translation
Peptide hormones and catecholamines act on cell surface receptors and activate secondary messengers (rapid)
Some hormones(bioactive) are further altered in target tissue to a more potent agonist within the same class or even to different class