Hormones

1- Classification of hormones:

* Water-soluble hormones

– Hormones catecholamines (adrenaline) -> derived from an amino acid (tyrosine)

– Peptide Hormones (hypothalamic hormones TRH …)

– Protein hormones (insulin)

* Fat soluble hormones

– Steroidal hormones (cortisol, testosterone) -> derivatives of cholesterol

– Thyroid hormones (thyroxine) -> derived from an amino acid (tyrosine)

2- Carriers:

– The fat-soluble hormones need a vehicle (carrier) to transport to the target cell. It is proteinaceous.

– Hormones related to their carrier are inactive and are not eliminated by the liver or kidney => hormone reservoir (> 90% of the total hormone).

– There are two types of carriers: non specific transporters (low affinity, many binding site) and specific carriers that attach That a single type hormone (high affinity (Kd low), limited number of binding sites )

3- Receivers:

* Common features

– Hormonal specificity (fixed only one type of hormone)

– A high affinity (structural complementarity)

– Number of sites in the limited cell (103 to 105)

– Organ specificity

– Reversibility of the interaction (non-covalent bonding)

* Note: the anti-hormones are molecules that have an analogy hormone structure; act competitively to occupy the hormone of sites but once fixed does not trigger a response.

4- Membrane Receptors:

A- G protein-coupled Receptors:

* G proteins are glycoproteins able to bind guanine nucleotides (GDP). Have three subunits (α, ß, γ) organized into seven transmembrane domains. The NH 2 portion is the extracellular side. The third intracellular loop and the large cytoplasmic hydrophilic terminal domain involved in receptor-G protein interaction Fixed α subunit the GDP

* The binding of ligand to receptor results in an exchange GDP -> GTP and dissociation of the α subunit -> α-GTP. The α-GTP complex will provide an activating or inhibitory signal to an effector -> second messenger …

* The G protein plays two roles: a role transduction (molecular switch) signal between the receiver and the enzymatic effector and a signal amplifying part

* There are many types of G protein (varying only α subunit)

– Protein Gs: stimulates adenylyl cyclase

– Protein Gi: inhibits adenylyl cyclase (M2 muscarinic receptor => bradycardia)

– Protein Gq: stimulates phospholipase C

Effector	2 messenger^ed	Action	r ECEIVER (Exp.)
Adenylyl cyclase	CAMP	Activation of protein kinase A (PKA) ® Protein phosphorylation	ß receptor
Phospholipase C (PLC)	IP3	Release of intracellular compartments Ca² ⁺ ions (sarcoplasmic reticulum)	₁ receiver
Phospholipase C	DAG	Activation of protein kinase C (PKC) dependent Ca² ⁺

* The limitation of action in second messenger is done by:

– Phosphodiesterase (phosphatase) => cAMP degradation (inhibited by theophylline)

– The Ca ++ ATPase pump at the plasma membrane, sarcoplasmic reticulum => decreased cytoplasmic Ca² +. (Also the exchanger Na + / Ca ++ -> heart)

* NB: the calcium pump in the mitochondria is slow and acts as a calcium reservoir and not too full of excitement / stop excitement.

* NB: the calcium ion acts as a second messenger. It can bind to a calciprotéine (calmodulin, troponin C) to activate an enzyme.

– Adrenergic receptors ß => Gs protein -> activates adenylyl cyclase -> cAMP elevation

– Adrenergic receptors α1 => Gq protein to the PLC -> IP3 -> Ca ++ elevation

– Adrenergic receptors α2 => Gi protein -> inhibits adenylyl cyclase -> down cAMP

* Some hormones induce desensitization after binding to their receptors. Receptor phosphorylation site queux C-terminal by a particular kinase (ß-ARK) prevents the binding of adrenaline to its beta receptor.