Which one of the following hormones is hydrophilic and has extracellular receptor?

Overview of Biochemical Endocrinology

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What hormones use extracellular membrane receptors?
Which of the following hormones is hydrophilic?
Where are hydrophilic hormone receptors?
Which hormone is water soluble and therefore binds to an extracellular receptor?

Hormone- "chemical substance secreted by a ductless gland into blood that is transported to a distant target organ whose activity it specifically affects".

Target Tissues- have receptors or specific binding proteins for each hormone

Properties of Hormones:

1. They are biosynthesized.
2. They operate at vanishingly small concentrations in blood (10-12 to 10-8 M, nano-pico).
3. They have short half lives.

4. They often exert multipoint control and operate at a number of target organs; hormones awaken existing potential in target cells that are preprogrammed to respond.
5. They are feedback regulated by: (a) themselves, (b) the product(s) of their action, (c) the central nervous system.

Chemistry

There are several chemically distinct classes of hormones: amine(epinephrine), peptide (insulin, glucagon) and steroid (cortisol).

Insulin, Glucagon, Epinephrine and Cortisol are the Hormones that Control Glucose Homeostasis:

Hormone Receptors:

Interaction between hormone and receptor forms the "hormone receptor complex".
Strength of binding is expressed as the dissociation constant Kd, the concentration at which the binding sites are half-saturated.

Classification of Hormones by Receptor Properties:

Group I: Hormones that bind to intracellular receptors: Glucocorticoids, mineralocorticoids, estrogens, progestins, androgens, vitamin D, thyroid, retinoic acid

Group II: Hormones that bind to cell surface receptors:

Group IIA: The second messenger is cAMP: vasopressin, glucagon, b-adrenergic catecholamines, somatostatin, opioids.

Group IIB: The second messengers are IP3 (inositol trisphosphate) / Ca2+ and diacylglycerol (DAG): oxytocin, angiotensin II, a-adrenergic catecholamines.

Group IIC: The cell surface receptor posses tyrosine protein kinase activity (intracellular messenger unknown): insulin, growth factors.

Group IIC': The cell surface receptor recruits soluble tyrosine kinases: growth hormone.

Group IID: The second messenger is cGMP: atrial natiuretic peptide (ANP).

General Features of Hormone Classes, Group I and Group II:

Feature	Group I	Group II
Solubility	Lipophilic	Hydrophilic
Plasma T1/2	Long (Hours to Days)	Short (Minutes)
Receptor Location	Intracellular	Plasma Membrane
Signal Mediator	Receptor-Hormone Comp.	cAMP,cGMP,Ca2+,IP3,DAG

Steroid / Thyroid / Retinoic Acid Hormone Actions:

Group I- lipophilic, derived from cholesterol (except thyroid and retinoic acid)
Passively diffuse through the plasma membrane of the target cell to associate with their receptors.
The hormone-receptor complex is assumed to be the intracellular messenger

Effects of these hormones are quite specific.

Cell Surface Acting Hormone Action:

Group II: peptide and amine hormones bind to membrane spanning receptors (7 transmembrane); communicate through second messengers, cAMP (Group IIA) or Ca2+ / IP3 / DAG (Group IIB).

G-Proteins

Review
E = The Effector Protein, Adenylate Cyclase
R = Receptor, 7-transmembrane cell surface receptor

Note: once the Effector protein is active the second messenger c-AMP is produced activating Protein Kinase A and starting a "cascade" of events leading to transmission of message and physiological / biochemical responses.

Hormones Functioning via IP3 / Ca2+ and DAG:

PIP2 = Phosphatidylinositol-4,5-bisphosphate
IP3 = Inositol-1,4,5-triphosphate
DAG = Diacylglycerol
PLC = Phospholipase C
PKC = Protein Kinase C
CaM Kinase = Calmodulin Kinase

[1] hormones bind to receptor
[2] receptor is coupled to phospholipase C by Gp
[3] Phospholipase C splits PIP2 into IP3 and DAG
[4] and [5] IP3 mobilizes intracellular (stored) Ca2+ from the ER for activation of CAM
[6] and [7] DAG activates protein kinase C which is further activated by Ca2+
[8]the concerted action of these two kinases elicit cellular responses

Clinical Correlate

Bacterial Toxins:

Cholera Toxin

Symptoms: watery stools, vomiting, cyanotic, low blood pressure, rapid / weak pulse
Treatment: IV solution of elctrolytes, tetracycline
Cause: cholera toxin inhibits GTPase preventing breakdown of GTP to GDP and locking the a subunit in the activated state producing a continuous oversupply of cAMP

Pertussis Toxin

Freezes Gi leaving Gs continuallt active, producing an oversupply of cAMP

What hormones use extracellular membrane receptors?

Peptide hormones, like neurotransmitters, are traditionally thought to activate cells by interacting with receptor sites accessible only from the extracellular space.

Which of the following hormones is hydrophilic?

Hydrophilic (water soluble) hormones like epinephrine, norepinephrine, dopamine, glucagon, and ADH, attach to receptors on the cell surface.

Where are hydrophilic hormone receptors?

Receptors may be outside or inside the target cell. Hydrophilic hormones are poorly lipid soluble and cannot pass through membranes – they bind with receptors on the outer cell membrane surface.

Which hormone is water soluble and therefore binds to an extracellular receptor?

Water-soluble hormone receptor activation: Water-soluble hormones, such as epinephrine, bind to a cell-surface localized receptor, initiating a signaling cascade using intracellular second messengers.