Endocrine PharmacologyEndocrine Pharmacology

Basic principlesBasic principles Endocrine SystemEndocrine System- Uses chemical signals (hormones) - Uses chemical signals (hormones)

for cell to cell communicationfor cell to cell communication- Coordinates the function of cells- Coordinates the function of cells- Response to an endocrine signal - Response to an endocrine signal

occurs within minutes to hours occurs within minutes to hours (ductless glands)(ductless glands)

HormonesHormones - Cell to cell communication - Cell to cell communication

moleculesmolecules- Made in glands or cells- Transported by blood- Distant or local target tissue

receptors- Activates physiological response

Hormonal regulation ↑↓Hormonal regulation ↑↓- Growth & development- Growth & development- Reproduction, fertility, sexual - Reproduction, fertility, sexual

functionfunction- Response to environmental - Response to environmental

situations (stress..)situations (stress..)- Maintenance of normal - Maintenance of normal

homeostasishomeostasis

Chemical nature of hormonesChemical nature of hormones- a. a derivatives:- a. a derivatives: T3; T4; Dopamine (precursor; T3; T4; Dopamine (precursor;

Tyrosine)Tyrosine)- Small peptides; polypeptides; large - Small peptides; polypeptides; large

proteins or glycoproteins:proteins or glycoproteins: Hypothalamic hormones; GH; PRL; Hypothalamic hormones; GH; PRL;

Insulin; Glucagon; LH; FSH; TSHInsulin; Glucagon; LH; FSH; TSH……..- Steroids- Steroids Cortisol; Aldosterone; Estrogen; Cortisol; Aldosterone; Estrogen;

Progesterone; AndrogensProgesterone; Androgens

Amine HormonesAmine Hormones - Derived from the amino acid tyrosine- Derived from the amino acid tyrosine- Include catecholamines (Dopamine) - Include catecholamines (Dopamine)

&&thyroid hormones thyroid hormones - Stored until secreted- Stored until secreted

* Receptor locations* Receptor locations Surface (Dopamine) Intracellular (nuclear; T3 & T4)

Protein and Polypeptide Protein and Polypeptide Hormones: Hormones: Synthesis and ReleaseSynthesis and Release

Protein and Polypeptide Hormone Protein and Polypeptide Hormone ReceptorsReceptors Bind to surface receptorBind to surface receptor TransductionTransduction

- System activation- System activation- Open ion channel

Enzyme activation Second messenger systems Protein synthesis

Steroid Hormones ReceptorsSteroid Hormones Receptors

Basal conditionsBasal conditions...minimal release...minimal release Stimuli:Stimuli:- Nerve impulse- Nerve impulse- Change in composition of ECF- Change in composition of ECF- Another hormone (trophic hormone)- Another hormone (trophic hormone) blood → target cells → receptors → blood → target cells → receptors →

initial change → cascade of reactions initial change → cascade of reactions → recognizable change→ recognizable change……

- Change in cell permeability- Change in cell permeability- Stimulation or inhibition of protein - Stimulation or inhibition of protein

synthesissynthesis ** Transcription or translation** Transcription or translation- Stimulation or inhibition of mediator - Stimulation or inhibition of mediator

releaserelease (second messenger)(second messenger) ** cAMP; DAG; Ca** cAMP; DAG; Ca++++ ; ITP (IP ; ITP (IP33)...)...

How long a hormone stays high in How long a hormone stays high in blood?blood?

Depends on:Depends on:- Extent of protein binding- Extent of protein binding- Efficiency of degradable enzymes & - Efficiency of degradable enzymes &

clearanceclearance Metabolism & excretionMetabolism & excretion- Efficiency of negative feedback - Efficiency of negative feedback

mechanismsmechanisms

CRH GnRHCRH GnRH - ↓ ↓ - ↓ ↓

- - ACTH LH; FSHACTH LH; FSH - ↓ ↓ - ↓ ↓

- - CortisolCortisol E E22; Progesterone; Progesterone

Sources of hormones:Sources of hormones:- Natural- Natural Human (GH; LH & FSH; hCG); Human (GH; LH & FSH; hCG);

Animal (Insulin, TAnimal (Insulin, T33 & T & T44))- Biosynthetic- Biosynthetic Insulin (Porcine & Bovine)Insulin (Porcine & Bovine)- Synthetic- Synthetic Most hormones and their Most hormones and their

antagonistsantagonists

Disorders affecting endocrine Disorders affecting endocrine glands:glands:

- Deficiency states- Deficiency states HRTHRT

- Excess production of a specific - Excess production of a specific hormonehormone

Inhibitors to the synthetic Inhibitors to the synthetic machinery ormachinery or

Release inhibitors orRelease inhibitors or Specific antagonistsSpecific antagonists

Clinical pharmacology of hormones:Clinical pharmacology of hormones:- Major clinical use of hormones- Major clinical use of hormonesHRT ( physiological doses)HRT ( physiological doses)- Supra-physiological doses - Supra-physiological doses

(pharmacological doses)(pharmacological doses)Anti-inflammatory effects (non-Anti-inflammatory effects (non-

endocrine-related diseases)...endocrine-related diseases)...- Use as diagnostic tool (TRH test ....)- Use as diagnostic tool (TRH test ....)

- The use of some drugs which are not - The use of some drugs which are not hormones, but used in the management hormones, but used in the management of diseases of endocrine originof diseases of endocrine origin

Antithyroid drugs, oral hypoglycemic Antithyroid drugs, oral hypoglycemic agentsagents……

- Some drugs are used to treat diseases - Some drugs are used to treat diseases not related to the endocrine system but not related to the endocrine system but affecting itaffecting it

Anticancerous drugs → ♂ & ♀ infertilityAnticancerous drugs → ♂ & ♀ infertility- The use of hormones as - The use of hormones as

contraceptives???contraceptives???