Endocrine system Pt 2 audio

Connection Between Hypothalamus & Anterior Pituitary

• Anatomical link: the stalk (a.k.a. infundibulum).
• Vascular link: hypophyseal portal system
  • Carries hypothalamic hormones ⇒ anterior pituitary (AP)
  • Carries AP-secreted hormones ⇒ general circulation
• Nomenclature reminder
  • "Releasing" in a hormone’s name ⇒ secreted by hypothalamus
  • "Stimulating" in a hormone’s name ⇒ secreted by anterior pituitary

Growth Hormone (GH)

• Abbreviations
  • $GH$ = growth hormone
  • $hGH$ = human (recombinant) GH, lab-produced
• Chemical class: amino-acid/peptide hormone (somatotropic)
• Direct actions (metabolic)
  • ↑ Lipolysis → ↑ plasma fatty acids for fuel
  • Anti-insulin effect → ↑ blood glucose, ↑ triglycerides
• Indirect actions (via IGF)
  • GH stimulates liver & bone to secrete IGF (Insulin-Like Growth Factor, a.k.a. somatomedin)
  • IGF ⇒
  • ↑ Chondroblast & chondrocyte activity → lengthwise bone growth
  • ↑ Osteoblast activity → bone thickening/remodeling
  • ↑ Protein synthesis in skeletal & smooth muscle → hypertrophy / hyperplasia
• Regulation
  • Hypothalamus
  • $GHRH$ (Growth Hormone-Releasing Hormone) ⇒ ↑ GH
  • $GHIH$ (Growth Hormone-Inhibiting Hormone) ⇒ ↓ GH
  • Classic negative feedback: ↑ IGF & ↑ GH inhibit GHRH / stimulate GHIH
• Clinical correlations
  • Hyposecretion
  • Newborn: hypoglycemia, delayed neural development
  • Child: pituitary dwarfism (treatable with recombinant hGH)
  • Adult: loss of lean mass, age-related sarcopenia
  • Hypersecretion (usually AP tumor)
  • Child: gigantism (very tall, ↑ glucose, ↑ triglycerides, mandibular/brow enlargement)
  • Adult (plates sealed): acromegaly → enlarged hands, feet, jaw, brow, soft-tissue growth

Prolactin (PRL)

• Secreted by anterior pituitary; peptide hormone
• Primary target: mammary glands → lactation (milk production)
• Regulation
  • Hypothalamus secretes $PIH$ (Prolactin-Inhibiting Hormone = dopamine) continuously
  • Nipple stimulation / suckling ⇒ ↓ PIH ⇒ ↑ PRL
  • High estrogen levels (pregnancy, mid-cycle) → ↓ PIH & ↑ PRL
• Additional points
  • Milk production ramps gradually; initial colostrum ~ first 48 h postpartum
  • Weaning: cessation of suckling halts PRL over ~1 week (pain/tenderness; cold compresses help)
  • Hyperprolactinemia in males → impotence; in either sex can cause galactorrhea

Thyroid Hormone (TH)

Gland Anatomy & Hormones

• Butterfly-shaped gland over trachea; lobes joined by isthmus
• Highly vascular; contains embedded parathyroids (separate topic)
• Secretes:
  • T₃ = triiodothyronine
  • T₄ = thyroxine
  • Calcitonin (covered with Ca²⁺ homeostasis)
• TH is a lipid-soluble amino-acid derivative (exception: crosses membranes → intracellular receptors)
• Iodine required (public-health addition to table salt)

Hypothalamic–Pituitary–Thyroid (HPT) Axis

$\text{Hypothalamus}\xrightarrow{TRH}\text{Anterior Pituitary}\xrightarrow{TSH}\text{Thyroid Gland}\xrightarrow{T₃/T₄}\text{Target Tissues}$

• $TRH$ = Thyrotropin-Releasing Hormone (hypothalamus)
• $TSH$ = Thyroid-Stimulating Hormone (anterior pituitary)
• Negative feedback: ↑ T₃/T₄ ⇒ ↓ TRH, ↓ TSH
• Note: TSH can secondarily ↑ PRL

Physiological Roles

• ↑ Basal metabolic rate, heat production
• Permissive for GH, reproductive hormones, neural development

Disorders

• Hypothyroidism
  • Iodine deficiency (diet) → ↓ T₃/T₄, loss of feedback, thyroid hypertrophy ⇒ Goiter
  • Children: cretinism → low growth, delayed neural & reproductive development, dry/scaly skin
  • Adults: lethargy, weight gain, cold intolerance; treated with synthetic TH (e.g., Synthroid)
• Hyperthyroidism
  • Graves’ disease (autoimmune; antibodies mimic TSH)
  • ↑ TH, goiter, weight loss, exophthalmos ("thyroid eye disease")
  • Hashimoto’s: transient hyper → eventual hypo (destructive autoimmunity)
  • Treatment: radioactive iodine ablation or surgery → lifelong TH replacement

Adrenal Cortex & Cortisol

Cortex Zones & Steroids

• Zona glomerulosa → mineralocorticoids (aldosterone)
• Zona fasciculata → glucocorticoids (cortisol)
• Zona reticularis → androgens (testosterone precursors)
  (Only adrenal cortex & gonads produce steroids)

Hypothalamic–Pituitary–Adrenal (HPA) Axis

$\text{Hypothalamus}\xrightarrow{CRH}\text{Anterior Pituitary}\xrightarrow{ACTH}\text{Adrenal Cortex}\xrightarrow{Cortisol}\text{Targets}$

• $CRH$ = Corticotropin-Releasing Hormone
• $ACTH$ = Adrenocorticotropic Hormone
• Normal circadian rhythm:
  • Low during sleep; rises ~2 h pre-awakening; peaks mid-morning; declines by evening
• Stress response: emotional or physical stress ⇒ sustained CRH, ACTH, cortisol; overrides feedback

Cortisol Actions

1. $\uparrow$ Gluconeogenesis (liver) → ↑ blood glucose
2. $\uparrow$ Lipolysis → ↑ plasma fatty acids (muscle fuel)
3. Proteolysis (muscle) → amino acids for gluconeogenesis
4. Temporary insulin resistance → spares glucose for brain
5. Anti-inflammatory / immunosuppressive (clinical steroid shots, creams)
6. Vascular: maintains BP, modulates catecholamine sensitivity

Clinical Conditions

• Hyposecretion
  • Addison’s disease (often low ACTH) → cortisol & aldosterone deficiency; fatigue, hypotension, hyperpigmentation
• Hypersecretion / Excess
  • Cushing’s syndrome: high cortisol from any cause (e.g., prednisone therapy)
  • Cushing’s disease: ACTH-secreting pituitary tumor
  • Signs: hyperglycemia, muscle atrophy, osteoporosis, poor wound healing, "moon face," "buffalo hump," central obesity, edema
• Pharmacology
  • Prednisone / other glucocorticoids for autoimmune flares; must taper to avoid adrenal insufficiency

Key Numerical / Biochemical Facts

• GH indirect mediator: $IGF_1 \approx 90\%$ liver-derived
• Thyroid hormone requires $\ge 150\,\mu g$ iodine/day (adult RDA)
• Cortisol circadian peak ≈ $15\text{–}20\,\mu g/dL$; nadir < $5\,\mu g/dL$ (un-stressed)

Integrative & Real-World Connections

• Public-health success: iodized salt virtually eradicated endemic goiter/cretinism in the U.S. "Goiter Belt"
• Performance enhancement: athletes abused GH/IGF for recovery; risks include acromegalic features & metabolic syndrome
• Stress management: chronic HPA activation linked to cardiovascular disease, obesity, insomnia
• Endocrine pharmacology: topical/systemic corticosteroids exploit anti-inflammatory property but carry catabolic & metabolic side-effects

Ethical / Practical Implications Discussed

• Historical inequity: early GH treatment required killing primates ⇒ only wealthy families accessed therapy, risk of simian viruses
• Over-the-counter "natural" salts (kosher, sea, rock) often lack iodine ⇒ resurgence of mild iodine deficiency
• Use of radioactive iodine to ablate thyroid in hyperthyroid cases (balance between curing disease & inducing lifelong hormone dependence)