Introduction to Endocrine Pharmacology

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Introduction to Endocrine Pharmacology

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Endocrine system

• Hormone-producing cells
• Circulating hormone
• Endocrine target cells

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Hormones

• A substance that is release in one tissue and
  travels through the circulation (usually) to the
  target tissue.

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Hormones

• Brain
• Gonadotropin-releasing hormone (GnRH)
• Pituitary hormone
• follicle-stimulating hormone (FSH)
• luetinizing hormone (LH)
• Thyroid gland T3, T4

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Hormones

• Adrenal gland
• glucocorticoid, mineralocorticoid
• Pancrease
• insulin
• Ovary
• estrogen, progesterone
• GIT
• gastrin
• Kidney
• renin, erythropoietin

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Types of Hormones

• Amino acid analogues derivatives
• thyroid hormones, catecholamines
• Polypeptides
• insulin, parathyroid hormone
• Lipid
• steroids, estrogen, progesterone

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1. Hormone-producing cells

• Localized
• discrete gland
• dispersed throughout a larger organ
• Store the hormone in intracellular granules for
  release (insulin)
• Release to stimulation by increasing synthesis
  (steroid hormone)

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Regulation of Hormonal Secretion

• By another hormone
• corticotropin cortisol
• By neural influences
• Cholinergic stimulation of catecholamine release
  from the adrenal medulla
• Concentration of a circulating ion or metabolite
  
• Ionized calcium parathyroid hormone
• By all 3 kinds
• Insulin-secreting beta cells of pancreatic islets

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2. Circulating Hormone

• Chemical structure of a hormone
• Distribution
• Degradation
• Excretion
• Specific carrier protein
• Sex steroids (SHBG)
• Cortisol (CBG)

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3. Endocrine target cells

• Specific hormone receptors
• Postreceptor events
• Gene-active hormones
• Membrane active hormones

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Drug actions on hormone-producing cells

• 1. Act via hormone receptors

Drug Action Clinical use OC ? GN Prevent
ovulation Bromocriptine ? Prolactin
Prolactinoma
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Drug actions on hormone-producing cells

• 2. Do not act via hormone receptors

Drug Action Clinical use SU ? insulin
DM Iodide ? T3, T4 Thyrotoxicosis Thionamides
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Drug that act on endocrine target cellsBinding
to receptors

• Post receptor of hormone action
• 1. Gene-active hormones
• Steroid hormones
• Synthesis mRNA

? Synthesis of proteins (lag period)
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Drug that act on endocrine target cellsBinding
to receptors

• Post receptor of hormone action
• 2. Membrane-Active Hormones
• Peptide hormone (FSH, LH)
• Biogenic amines

Act by stimulating cAMP synthesis
Adrenocorticotropic hormone (ACTH)
Follicle-stimulating hormone (FSH)
Luteinizing hormone (LH)
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Other mechanism

• adenylate cyclase activity
• PGE1 in adipose tissue
• Stimulate tyrosine-specific protein
  phosphorylation
• insulin

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cAMP dependent phosphorylation

• Rapid response (within seconds)
• only requires activation of enzymes already
  present in the cell
• Disappearance of the hormone is rapidly

• disappearance of its effect
• degradation of cAMP by phosphodiesterase
• dephosphorylation of kinase substrates by
  phosphatase

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Hormone transport

• Polypeptide
• largely as free entities
• Steroid thyroid hormone
• largely bound to plasma protein 1-10 is free

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Metabolism of hormones

• Polypeptide
• Broken down to their component amino acid in the
  plasma
• Tissue proteases peptidase
• Thyroid hormones
• Metabolized largely by deiodination in peripheral
  tissues
• Steroid hormones
• Metabolized conjugation (liver) urine