Endocrine System and Regulation of Metabolism

Comparison of Nervous and Endocrine Regulatory Systems

• Nervous System: Uses neurotransmitters acting locally across synapses; action timeframe and duration are within milliseconds.

• Endocrine System: Uses hormones secreted into body fluids and transported via bloodstream to distant targets; action timeframe ranges from seconds to days, with prolonged duration (minutes to weeks).

General Characteristics of Endocrine Glands and Hormones

• Mechanism: Ductless glands secrete hormones into interstitial fluid and blood plasma to bind specific protein receptors on target cells.

• Distances of Signaling:

  1. Circulating Hormones: Transported via blood to distant target tissues.

  2. Paracrine Signaling: Local hormones binding neighboring target cells.

  3. Autocrine Signaling: Local hormones binding receptors on the cell that secreted them.

• Primary Cellular Responses: Regulates rate of enzymatic reactions, transmembrane transport of ions/molecules, and gene expression/protein synthesis.

• Specificity: Hormones interact exclusively with target cells expressing matched receptors (e.g., TSH binds thyroid follicular cells, not pancreatic islets).

Chemical Classes and Synthesis of Hormones

• Lipid-Soluble Hormones (Steroids, Thyroid Hormones, $NO$):

  • Transported in blood bound to carrier proteins; orally effective as they pass through intestinal membranes without digestion.

  • Bind intracellular receptors to act as transcription factors on DNA; exhibit slow onset and long half-lives ($t_{1/2}$).

• Water-Soluble Hormones (Peptides, Proteins, Amines, Eicosanoids):

  • Circulate freely in plasma; destroyed by digestive enzymes (must be injected).

  • Bind transmembrane cell-surface receptors, triggering intracellular G-proteins, second messengers ($cAMP$, $IP_3$\/DAG, $Ca^{2+}$), and rapid protein phosphorylation.

• Peptide Synthesis Pathway: Preprohormone (ribosomes) $\rightarrow$ Prohormone (rough ER) $\rightarrow$ Active hormone (Golgi packaging into secretory vesicles).

Pituitary Gland Anatomy and Hypothalamic Control

• Posterior Pituitary (Neurohypophysis): Neural tissue connected via the hypothalamo-hypophyseal tract. Releases ADH (promotes renal water retention and vasoconstriction) and Oxytocin (stimulates uterine contractions and milk ejection).

• Anterior Pituitary (Adenohypophysis): Glandular tissue connected via the Hypothalamic-Hypophyseal Portal System. Hypothalamic trophic neurohormones deliver directly to control release of TSH, ACTH, GH, Prolactin, FSH, and LH.

Patterns of Hormonal Interaction

1. Synergism: Combined hormone effect is greater than the sum of separate individual effects (e.g., Glucagon + Epinephrine + Cortisol on blood glucose).

2. Permissiveness: A hormone requires the presence of a second hormone to exert its full effect (e.g., Thyroid hormone is permissive for GH activity).

3. Antagonism: One hormone directly opposes the action of another (e.g., Glucagon vs. Insulin).

Endocrine Pathologies

• Etiologies: Hypersecretion (tumors\/cancer), Hyposecretion (gland destruction\/deficiencies), or target cell unresponsiveness (receptor downregulation\/post-receptor defects).

• Classification:

  • Primary Pathology: Dysfunction originates in the final endocrine gland.

  • Secondary Pathology: Dysfunction originates in trophic tissue (pituitary or hypothalamus).

Adrenal Gland Structure and Physiology

• Adrenal Cortex (Glandular):

  • Zona Glomerulosa: Secretes Mineralocorticoids (Aldosterone) for renal $Na^+$ retention and $K^+$ excretion.

  • Zona Fasciculata: Secretes Glucocorticoids (Cortisol) via HPA axis ($\text{CRH} \rightarrow \text{ACTH} \rightarrow \text{Cortisol}$); promotes gluconeogenesis, lipolysis, protein breakdown, anti-inflammatory effects, and negative calcium balance.

  • Zona Reticularis: Secretes weak adrenal androgens (DHEA).

• Adrenal Medulla (Neural): Chromaffin cells secrete Epinephrine (80%) and Norepinephrine (20%) during sympathetic excitation.

• Pathologies: Cushing's Syndrome (hypercortisolism; trunk obesity, "moon face") vs. Addison's Disease (hypocortisolism; hyponatremia, hyperkalemia, skin hyperpigmentation).

Thyroid Gland Physiology

• Structure & Function: Follicular cells produce $T_3$ and $T_4$ (establishes BMR, increases catecholamine sensitivity, aids growth\/neurodevelopment). Parafollicular C cells produce Calcitonin (lowers plasma $Ca^{2+}$).

• Regulation: Hypothalamic TRH $\rightarrow$ Pituitary TSH $\rightarrow$ Thyroid $T_3$\/$T_4$ (exerts negative feedback).

• Pathologies: Hyperthyroidism (Graves' disease; heat intolerance, exophthalmos, tachycardia) vs. Hypothyroidism (goiter, cold intolerance, myxedema, cretinism in infants).

Growth Physiology and Growth Hormone (GH)

• Regulation: Hypothalamic GHRH (+) and Somatostatin (-) regulate anterior pituitary GH. GH induces tissue growth and hepatic IGF-I release.

• Essential Factors: Requires adequate nutrition, absence of chronic stress, and permissive levels of thyroid hormone and insulin.

• Pathologies: Pituitary Dwarfism (childhood deficiency), Gigantism (childhood oversecretion), Acromegaly (adult oversecretion causing bone thickening and organ enlargement).

Calcium and Phosphate Homeostasis

• Bone Dynamics: Osteoblasts deposit matrix; Osteoclasts resorb bone matrix by secreting $HCl$ and cathepsin K.

• Hormonal Regulation:

  • Parathyroid Hormone (PTH): Secreted in response to hypocalcemia; increases blood $Ca^{2+}$ via bone resorption, renal $Ca^{2+}$ reabsorption, and activation of Calcitriol.

  • Calcitriol ($1,25\text{-dihydroxyvitamin D}_3$): Increases intestinal absorption of dietary $Ca^{2+}$.

  • Calcitonin: Secreted during hypercalcemia; inhibits osteoclastic bone resorption.

• Pathology: Osteoporosis occurs when bone resorption exceeds deposition.

Regulation of Metabolism, Fed vs. Fasted States, and Diabetes

• Appetite & Metabolic Rate: Hypothalamic Feeding and Satiety Centers regulate intake. Basal Metabolic Rate (BMR) is determined by muscle mass, age, gender, and hormones ($T_3$\/$T_4$, catecholamines).

• Metabolic States:

  • Fed State (Anabolic / Insulin Dominant): Promotes glucose oxidation, glycogenesis, lipogenesis, and protein synthesis.

  • Fasted State (Catabolic / Glucagon Dominant): Maintains plasma glucose ($70\text{--}110\,\text{mg/dL}$) via hepatic glycogenolysis, gluconeogenesis, lipolysis, and ketogenesis.

• Pathologies:

  • Type 1 Diabetes: Autoimmune beta-cell destruction leading to severe insulin deficiency, hyperglycemia, glucosuria, polyuria, polydipsia, polyphagia, and DKA.

  • Type 2 Diabetes: Skeletal muscle and hepatic insulin resistance combined with progressive beta-cell failure.

  • Metabolic Syndrome: Diagnosis requires meeting $\ge 3$ of 5 criteria: central obesity, elevated blood pressure ($\ge 130/85\,\text{mmHg}$), fasting hyperglycemia ($\ge 110\,\text{mg/dL}$), high triglycerides, and low HDL.

Thermoregulation

• Hypothalamic Thermoregulatory Center: Integrates peripheral and central thermoreceptor inputs to maintain core temperature ($37\,^{\circ}\text{C}$).

• Heat Loss Mechanisms: Cutaneous vasodilation and sympathetic cholinergic sweat gland activation.

• Heat Gain\/Retention Mechanisms: Cutaneous vasoconstriction, somatic motor shivering thermogenesis, and brown fat non-shivering thermogenesis via uncoupling protein UCP-1.

• Thermoneutral Zone: Environmental range of $27.8\text{--}30\,^{\circ}\text{C}$ where core temperature is sustained purely by vasomotor control.