Endocrine Pharmacology

Question 1

What are hormones?

Answer 1

• Hormones are chemical messengers (signals) involved in the regulation and coordination of bodily functions through cell-cell communication
• Hormones can act locally to affect themselves (Autocrine)
• Hormones can act locally to affect nearby cells (Paracrine)
• Hormones secreted by neurons (Neuroendocrinology) can act as neurotransmitters (short distances; synapses eg. ACh) or neurohormones (secreted into blood stream; oxytocin, epinephrine)
• Hormones can be secreted by cells to enter the bloodstream to affect distant target cells (endocrine)

Question 2

What is autocrine signaling?

Answer 2

• Hormones can act locally to affect themselves
• Growth factors
• Cytokines

Question 3

What is paracrine signaling?

Answer 3

• Hormones can act locally to affect nearby cells
• Nitric Oxide
• Cytokines
• Endothelins
• Insulin
• Insulin-like growth factors (IGF’s)

Question 4

What is Endocrine Signaling?

Answer 4

• Hormones can be secreted by cells to enter the bloodstream to affect distant target cells
• Thyroxine
• Insulin
• Estrogen
• Renin
• IGF’s

Question 5

What is intracrine signaling?

Answer 5

• Refers to a hormone that acts inside a cell, regulating intracellular events
• Passes the cell membrane without the use of a receptor (like estrogen)

Question 6

Endocrine hormones: Synthesis (3)

Answer 6

• Amines: catecholamines, thyroid hormone (tyrosine derivative); stored for release
• Peptides-Proteins; insulin, growth hormone, and the gonadotrophins; stored for release
• Steroids; sex steroids, corticosteroids, Vit D cholesterol precursor, lipophilic
  - Not stored; released immediately
  -Typically have delayed biologic effects

Question 7

Endocrine hormones: Release

Answer 7

• Constitutive (basal); insulin, cortisol, thyroxine
• Stimulated (environment, higher CNS); insulin, cortisol
• Pulsatile; hypothalamic releasing hormones
• Circadian rhythms; cortisol, thyroxine

Question 8

Endocrine hormones: pharmacokinetics

Answer 8

• Most travel in bloodstream bound to proteins
  - Hormone binding globulins eg. ABG, TBG
  - Renders hormone inactive; storage pool
  - Maintains strict control over [free hormone]
  - Protects hormone from metabolism
  - Bound hormone ⇌ free hormone
• Free hormone usually has short plasma half-life, seconds to minutes
• Biologic effects can persist after hormone has been metabolized/inactivated
• Most circulating hormones metabolized by liver then excreted in bile or urine

Question 9

Describe hormone receptors and affinity of ligand binding

Answer 9

• Receptors and hormone (ligand) binding
  - Affinity of Ligand for Receptor contributes to potency; specificity can be controlled by making ligands/drugs that have greater or lesser specificity for interaction with the receptor
• Receptors represent key points of drug intervention
  - Agonists and antagonists

Question 10

What are the receptor types that hormones utilize?

Answer 10

1. Cell surface receptors
   - G-protein receptors (channels, second messenger)
   - Growth factors, insulin, IGF’s
   - Protein, polypeptides, amines; less lipophilic
   - Ligand binding and signal transduction for intracellular response
   - Response is usually rapid and may be essentially immediate
2. Nuclear and cytosolic receptors
   - Steroids, thyroid, Vitamin D, retinoic acid
   - Ligands are lipophilic
   - Ligand binding and transcription for response
   - Delay in response

Question 11

Endocrine System components

Answer 11

1. Traditional/Classic Endocrine System, Regulated by CNS feedback loops
   - Hypothalamus-Anterior Pituitary-Target Gland Axes Gonads, Thyroid, Adrenal Cortex
2. “Independent” Endocrine Glands
   - Pancreas
   - Posterior Pituitary Parathyroids
3. Dispersed Endocrine Cells
   - IGF’s – liver
   - GI hormones
   - Renin-kidney

Question 12

Hypothalamic-Anterior Pituitary Hormones – Releasing and Stimulating Hormones

Answer 12

Question 13

Summary of Hypothalamic-Anterior Pituitary-Endocrine Organs - Release and Stimulating Hormones

Answer 13

• Releasing hormones (RH’s) and stimulating hormones (SH’s) are peptides, proteins, or amines
• RH’s and SH’s usually bind to G-protein coupled receptors to produce their effects

Question 14

Describe the regulation of hormones - regulation of the Hypothalamic-Anterior Pituitary- Organ Axes

Answer 14

Question 16

What are the clinical applications of endocrine drugs for non-endocrine diseases (2)

Answer 16

Glucocorticoids:
- Inflammation
- Allergy diseases
- Shock (septic)?
- Immunosuppression (organ transplant rejection)
Cancer Therapy:
- Glucocorticoids-antilymphocyte effects in certain hematologic malignancies
- Lymphoma
- Multiple myelomas
- Anti-estrogens bind to increased estrogen in the therapy of breast cancer
- anti-androgens bind to increased androgen receptors in the therapy of prostate cancer

Question 17

What are clinical applications of endocrine drugs - Additional endocrine uses (5)

Answer 17

• Contraceptives
• Abortifacients; labour induction at the end of pregnancy
• Osteoporosis prevention
• Reproductive technology (superovulation)
• Behaviour modification (aggression)

Question 18

What are clinical applications of endocrine drugs - Endocrine diseases

Answer 18

Reflex Pathway Dysfunction: Etiologies
Hormone hypersecretion:
- Primary (adrenal adenoma) or secondary (pituitary adenoma) tumors
Hormone hyposecretion:
- Primary gland malfunction
- Autoimmune destruction (diabetes, thyroid)
- Congenital or surgery (thyroid, gonads)
- Age-dependent atrophy (gonads)
- Toxicities or nutritional basis (thyroid)
- Secondary or tertiary gland malfunction possible
Inappropriate target tissue response:
- Receptor expression abnormalities (ovarian tumors expressing GnRH receptors)
- Mutated receptors
- Iatrogenic; drug therapy (insulin, glucocorticoids)