Memory tricks for hormones and feedback loops

Lipid-soluble hormones (steroids, thyroid hormones, vitamin D) cross the cell membrane freely and bind intracellular receptors → receptor-hormone complex enters nucleus → binds DNA → changes gene expression. Slow but long-lasting. Water-soluble hormones (peptides, catecholamines) cannot cross the membrane — bind surface receptors → activate second messengers (cAMP, IP3, DAG, Ca2+) → rapid cellular response. Fast but short-lived. This distinction determines onset, duration, and mechanism of action of every hormone class.

cAMP pathway: Gs-coupled receptor → adenylyl cyclase → cAMP → PKA → phosphorylates target proteins. Examples: epinephrine (beta), glucagon, TSH. Gq pathway: receptor → phospholipase C → IP3 + DAG. IP3 → ER releases Ca2+. DAG → activates PKC. Examples: epinephrine (alpha-1), angiotensin II, oxytocin. Gi pathway: inhibits adenylyl cyclase → decreases cAMP. Examples: epinephrine (alpha-2), somatostatin. RTK pathway: insulin, growth factors → tyrosine phosphorylation cascade.

After a meal: blood glucose rises → insulin (beta cells) dominates → glucose uptake by liver, muscle, fat → glycogen synthesis → fat storage → protein synthesis. During fasting: blood glucose falls → glucagon + cortisol + growth hormone + epinephrine → glycogenolysis (break down glycogen) + gluconeogenesis (make new glucose from amino acids, lactate, glycerol) + lipolysis (break down fat) → blood glucose maintained. The Somogyi effect: overnight hypoglycemia → counter-regulatory hormone surge → morning hyperglycemia. Treat by reducing evening insulin, not increasing it.

Insulin binds its receptor tyrosine kinase → receptor phosphorylates itself → activates IRS proteins → PI3-kinase → Akt (PKB) → GLUT4 transporter vesicles move from intracellular stores to the plasma membrane → GLUT4 inserts → glucose enters cell by facilitated diffusion. GLUT4 is found in muscle and adipose tissue — the major insulin-sensitive tissues. Liver uses GLUT2 (always open, insulin-independent). Brain uses GLUT3 (always open — brain doesn't need insulin for glucose uptake). Insulin resistance: Akt signaling impaired → GLUT4 doesn't translocate → glucose can't enter → Type 2 diabetes.

T4 is the main secreted form but T3 is 3–4× more potent. T4 is converted to T3 by deiodinase enzymes in peripheral tissues (liver, kidney, muscle). T3 binds nuclear thyroid hormone receptors → activates gene transcription → increases: basal metabolic rate (BMR), O2 consumption, heat production, heart rate and contractility, carbohydrate and fat metabolism, protein synthesis and degradation, CNS development (critical in fetus). Propylthiouracil (PTU) blocks thyroid hormone synthesis AND peripheral T4→T3 conversion — used in thyroid storm. Methimazole blocks synthesis only.

Stress activates the HPA axis: CRH (hypothalamus) → ACTH (anterior pituitary) → cortisol (adrenal cortex zona fasciculata). Cortisol prepares the body for stress by: raising blood glucose (gluconeogenesis), suppressing the immune system (anti-inflammatory), suppressing reproductive and growth functions, increasing alertness. Negative feedback: cortisol suppresses CRH and ACTH — the off switch. Diurnal rhythm: cortisol peaks at 8 AM, lowest at midnight. Chronic stress → chronically elevated cortisol → muscle wasting, immunosuppression, hyperglycemia, central obesity, poor wound healing.

GH (somatotropin) from anterior pituitary has two types of effects. Direct effects: metabolic — lipolysis (breaks down fat), decreases glucose uptake (anti-insulin/diabetogenic), protein synthesis. Indirect effects via IGF-1 (insulin-like growth factor 1, from liver): linear bone growth (chondrocyte proliferation), organ growth. GH secretion is pulsatile — highest during deep sleep (delta sleep), exercise, fasting, hypoglycemia. Suppressed by: hyperglycemia (IGF-1 negative feedback), obesity, somatostatin. Deficiency in childhood → dwarfism. Excess before epiphyseal closure → gigantism. Excess after closure → acromegaly.

When Ca2+ falls: parathyroid glands release PTH → acts on three targets simultaneously. Bone: activates osteoclasts → bone resorption → Ca2+ + phosphate released. Kidney: increases Ca2+ reabsorption in DCT, decreases phosphate reabsorption (prevents Ca-phosphate precipitation), activates 1-alpha-hydroxylase (converts vitamin D to active form). Gut: via activated vitamin D → increases Ca2+ absorption from diet. Net result: blood Ca2+ rises. When Ca2+ rises: calcitonin from thyroid C cells inhibits osteoclasts → lowers Ca2+. PTH and calcitonin are physiological antagonists.

Type 1 DM: autoimmune destruction of beta cells → absolute insulin deficiency → cells starve despite high blood glucose → glucagon unopposed → lipolysis → ketone body production → diabetic ketoacidosis (DKA). Treatment: insulin replacement. Type 2 DM: insulin resistance (cells don't respond) → compensatory hyperinsulinemia → beta cells eventually fail → relative insulin deficiency. Usually no DKA (some insulin present to suppress glucagon/ketones). Hyperglycemia → glucosuria → osmotic diuresis → polyuria, polydipsia, polyphagia (the 3 Ps). Chronic hyperglycemia → glycation → vascular damage → retinopathy, nephropathy, neuropathy.