Endocrine System Overview
Definition:
The endocrine system consists of glands that secrete hormones directly into the bloodstream to regulate various bodily functions such as metabolism, growth, reproduction, and stress responses.
Major Endocrine Glands:
Pituitary, thyroid, parathyroid, adrenal glands, pancreas, gonads (testes/ovaries).
Hormone Synthesis and Secretion
Synthesis:
Hormones are synthesized in specific endocrine cells. For example:
APeptide hormones (e.g., insulin) are synthesized as preprohormones, cleaved into prohormones, and finally processed into active hormones.
Steroid hormones (e.g., cortisol) are synthesized from cholesterol.
Amino acid derivatives (e.g., thyroid hormones) are derived from tyrosine.
Secretion:
Typically regulated by feedback loops (negative or positive). Example: Hypothalamic-pituitary-end organ axis.
Mechanisms of Hormone Action
Cell Surface Receptors: Peptide hormones bind to membrane receptors, triggering second messenger pathways (e.g., cAMP, IP3/DAG).
Intracellular Receptors: Steroid and thyroid hormones diffuse into cells to bind cytoplasmic or nuclear receptors, altering gene transcription.
Principles of Endocrine Drug Therapy
Hormone Replacement: For deficiencies (e.g., insulin for diabetes).
Hormone Inhibition: To reduce excess hormone levels (e.g., methimazole for hyperthyroidism).
Receptor Modulation: Agonists or antagonists modulate receptor activity (e.g., selective estrogen receptor modulators).
Pharmacokinetics and Pharmacodynamics
Pharmacokinetics (PK):
Involves the absorption, distribution, metabolism, and excretion (ADME) of endocrine drugs.
For example, oral thyroid hormones are absorbed in the gastrointestinal tract and may require conversion in the liver.
Pharmacodynamics (PD):
Relates to the drug's mechanisms of action and its effects on the body.
Endocrine drugs often act as hormone analogues or antagonists, binding to specific receptors to mimic or inhibit natural hormone actions.
Receptor Types, Agonists, and Antagonists
Receptors: Intracellular (e.g., steroid) or membrane-bound (e.g., peptide).
Agonists: Mimic hormones (e.g., levothyroxine for thyroid hormone replacement).
Antagonists: Block hormones (e.g., somatostatin analogues inhibit GH).
Feedback Mechanisms and Homeostasis
Feedback Mechanisms and Homeostasis Endocrine systems use primarily negative feedback to maintain balance.
Drugs often restore or modulate feedback mechanisms (e.g., cortisol suppresses ACTH via negative feedback).
Therapeutic Uses and Side Effects
Uses: Treat hypothyroidism, diabetes, adrenal insufficiency, and hormonal cancers.
Side Effects: Systemic effects like osteoporosis (corticosteroids) or hypoglycemia (insulin).