Endocrine System Physiology

Physiology of Endocrine System

• Endocrinology is the study of endocrine glands and their functions.
• The endocrine system is a control system in the body.
• The endocrine system controls:
  • Development and growth.
  • Energy regulation (storage and mobilization).
  • Internal homeostasis (fluids and ions).
  • Reproduction (menstruation, pregnancy, lactation).
  • Control responses to stress and the immune system.
• Other functions include:
  • Controlling heart rate and blood pressure through catecholamines and thyroxine.
  • Regulating appetite and sleep-wake cycles via leptin and melatonin.

Endocrine Glands and Organs

• Endocrine glands are ductless glands that secrete hormones directly into the bloodstream.
• Endocrine glands and organs are groups of cells, secreting hormones into the interstitial fluid or blood, targeting specific organs or tissues.

Major Endocrine Organs

• The hypothalamus is a major endocrine organ, also part of the nervous system.
• Endocrine cells in other organs produce and release hormones, adding to their function (liver, kidney, gastrointestinal tract, heart, pineal gland, placenta, and skin).

Major Endocrine Glands & Organs - Hypothalamus

• Part of the nervous system.
• A connection between nervous and endocrine systems.
• Connected to the pituitary gland.
• Controls the anterior pituitary gland through releasing and inhibitory hormones (hypothalamic-hypophyseal portal circulation).
• Secretes hormones to the posterior pituitary gland via the hypothalamo-hypophyseal tract (ADH via the supraoptic nucleus, oxytocin via the paraventricular nucleus).
• Regulates adrenal medulla that secretes adrenaline and noradrenaline.

Major Endocrine Glands & Organs - Pituitary Gland

• The pituitary gland (hypophysis) consists of anterior and posterior lobes.
• Anterior pituitary (adenohypophysis) controls other glands (thyroid gland, adrenal cortex, gonads).
• Posterior pituitary (neurohypophysis) stores and releases ADH and oxytocin.

Major Endocrine Glands & Organs - Other

• Liver
  • Secretes erythropoietin, somatomedins, and vitamin D (calcidiol)
• Kidney
  • Secretes erythropoietin , and active vitamin D (calcitriol).
• Gastrointestinal tract
  • Secretes hormones like gastrin, secretin, cholecystokinin (CCK).
• Heart
  • Secretes atrial natriuretic peptide (ANP).
• Pineal gland
  • Secretes melatonin.
• Placenta
  • Secretes hormones like estrogen, progesterone, relaxin, human chorionic gonadotropin (hCG) and human placental lactogen (hPL).
• Skin
  • Secretes leptin and vitamin D (cholecalciferol).
• Adipose tissue
  • Secretes leptin to regulate appetite and stimulate energy expenditure, and adiponectin to enhance insulin sensitivity.

Hormones

• Hormones are chemical substances released by groups of cells.
• Types of hormones:
  • Affect many different cell types.
  • Affect only specific target cells.
• Endocrine glands essential for life.
• Deficiency of their hormones may cause death.
  • Anterior lobe of the pituitary gland.
  • Adrenal cortex.
  • Parathyroid gland.
• Target cells contain specific receptors for hormones.

Endocrine Hormones

• Specific hormones (T3, T4, Calcitonin, Parathyroid Hormone, Insulin, Glucagon, Testosterone, Estrogen, Progesterone, Epinephrine, Glucocorticoids, Aldosterone, Melatonin) have specific functions and are regulated in various ways.

Chemical Messengers

• Endocrine: released by glands or specialized cells into the bloodstream and influence target tissues.
• Neuroendocrine: released by neurons into the bloodstream and influence target tissues.
• Paracrines: secreted by cells into the extracellular fluid to affect neighboring target cells.
• Autocrines: secreted by cells into the extracellular fluid to affect themselves. (Example: Insulin)

Hormone Classification

• Protein and peptide hormones: synthesized from amino acids; stored in secretory vesicles.
• Steroid hormones: derived from cholesterol; not stored; lipophilic, diffusing across cell membranes.
• Amine hormones: derived from tyrosine or tryptophan; behave as either peptide or as steroid hormones.

Classification of Stimuli

• Humoral stimuli: secretion of hormones in direct response to changing blood levels of ions and nutrients.
• Neural stimuli: nerve fibers stimulate hormone release.
• Hormonal stimuli: release of hormones in response to hormones produced by other endocrine glands.

Transport of Hormones

• Water-soluble hormones are transported freely in the blood.
• Lipid-soluble hormones travel in the blood bound to carrier proteins.

Receptors

• Large proteins.
• High specificity to one type of hormone.
• Located in cytoplasm or nucleus for lipophilic hormones
• Located on the cell membrane for hydrophilic hormones.

Regulation of Hormonal Receptors

• Up-regulation: increased receptor number.
• Down-regulation: decreased receptor number.

Mechanism of Actions of Hormones

• Hormones act on proteins.
  • Enzymes: activation of enzymes.
  • Channels: opening of channels.
• Lipid-soluble hormones often influence gene regulation (slow).
• Lipid-insoluble hormones generally affect protein activation (fast).

G-Protein

• Membrane protein.
• Connected to guanosine.
• Inactive when bound to GDP.
• Active when bound to GTP.
• Regulatory protein with two types:
  • Stimulatory G-proteins: stimulating enzymes, opening channels.
  • Inhibitory G-proteins: inhibiting enzymes and closing channels.

Mechanism of action of hormones & target tissue

• Peptide and protein hormones: Hormone-receptor interaction → enzyme activation → second messenger release (adenylate cyclase-cAMP, phospholipase C-IP3/DAG, calcium-calmodulin complex, or tyrosine kinase system) → cellular function changes.

A-Second Messenger (Adenylyl Cyclase-cAMP)

• Hormone binds with receptor.
• G-protein activation.
• cAMP generation.
• Protein kinase activation → cellular response.

B-Second Messenger (Phospholipase C-IP3)

• Hormone binds with receptor.
• G-protein activation.
• Phospholipase C activation → IP3 and DAG production.
• Calcium release from intracellular stores → cellular response.

C-Second Messenger (Calcium-Calmodulin Complex)

• Ca2+ influx.
• Ca2+-calmodulin complex formation.
• Activation of protein kinase → cellular response.

D-Second Messenger (Tyrosine Kinase System)

• Hormone binding → receptor dimerization.
• Receptor autophosphorylation → phosphorylation of other signaling molecules.
• Cellular response.

Transport of Steroid Hormones

• Are made from cholesterol.
• Are lipophilic & can enter target cells.
• Are immediately released from cell after synthesis.
• Interact with cytoplasmic receptors.
• Activate genes (DNA) for protein synthesis.
• Act after a longer half-time than peptide hormones.
• Examples: cortisol, estrogen, and testosterone.

Amine Hormones

• Derived from tyrosine or tryptophan (one type of amino acid).
• Three groups:
  1. Tryptophan → Melatonin
  2. Tyrosine → Catecholamines (behave like peptide hormones).
  3. Tyrosine → Thyroid hormones (behave like steroid hormones).

Regulation of Hormone Secretion

• Negative feedback: a hormone's action inhibits further secretion of the hormone.
  • Short loop: feedback directly on the chief gland.
  • Long loop: feedback goes all the way to the hypothalamus.
  • Ultra-short loop: the gland secretes a hormone to act on itself.
• Positive feedback: a hormone's action causes more secretion of the hormone.

Clearance of Hormones

• Rate of hormone secretion and removal.
• Metabolic destruction by tissues.
• Binding with tissues.
• Excretion into bile or urine.

Hypothalamus-Pituitary Axis

• Hypothalamus coordinates endocrine function.
• It controls growth, milk production, osmoregulation, and other glands using the hypothalamic-hypophyseal portal system/ portal vessels, and circulation.
• Hypothalamo-hypophyseal tract (neural tract/ neural axons).
• Hormonal secretion of hypothalamus to the portal system (anterior pituitary).
• Nervous signals from hypothalamus to a neural tract (posterior pituitary).

Posterior Pituitary Hormone (ADH)

• Synthesized as preprohormone.
• Synthesized and stored in the nerve cell bodies of the hypothalamus (supraoptic and paraventricular nuclei).
• Released into the bloodstream when stimulated.
• Acts mainly on the kidneys to increase water reabsorption and reduce urine output.

Receptors for ADH

• Three types (V1A, V1B, and V2).
  • V1A mediates vasoconstriction.
  • V1B is unique to anterior pituitary and mediates increased ACTH secretion.
  • V2 is located in the principle cells of distal convoluted tubule and collecting ducts, increasing water reabsorption.

Mechanism of Action of ADH

• Binds V2 receptors in distal convoluted and collecting tubules on peritubular surface.
• Activates adenylate cyclase and cAMP.
• Activates protein kinase A, causing insertion of aquaporin-2 channels in the luminal membrane.
• Increasing water permeability of collecting tubules allowing reabsorption in the kidney, increasing urine concentration and reducing water loss.

Osmotic Stimuli of ADH

• Increase in plasma solute (sodium) → Osmotic pressure stimulates hypothalamic osmoreceptors.
• Increases ADH secretion and thirst.
• Sensitive to changes in osmolality (1-2%).

Non-osmotic Stimuli: Volume Effects

• Low blood volume (hypovolemia), low blood pressure activates baroreceptors.
• Normally: baroreceptors tonically inhibit ADH.
• Reduction in blood pressure or volume activates baroreceptors → inhibits tonic inhibition and increases ADH release.

Non-osmotic Stimuli: Others

• Physiological stress (pain, trauma, surgical stress, emotional stress, fear), and alcohol intake increase ADH.

ADH Disorders

• Two types:
  1. Neurogenic (central): hypothalamic or neurohypophyseal failure to synthesize or secrete ADH.
  2. Nephrogenic: kidney failure to respond to ADH.
• Synthetic ADH ('desmopressin') treats neurogenic.

Oxytocin

• Synthesized and stored in the hypothalamus.
• Released in response to signals from sensory neurons.
• Function in milk ejection.
  • Stimulation causes contraction of myoepithelial cells around mammary alveoli.
• Function in childbirth (parturition).
  • Positive feedback from uterine muscle.
  • Intensifies uterine contractions until delivery is complete.
• Function in male ejaculation.
  • Relaxes and contracts smooth muscle in the vas deferens.

Regulation of Oxytocin

• Stimulate secretion:
  • Hugging, touching, orgasm (in both sexes).
  • Sounds of baby crying (in females).
  • Uterine contractions (in females).
  • Ejaculation (in males).
• Inhibit secretion:
  • Alcohol (in both sexes).

Physiology of Thyroid Gland, Thyroid Hormones (T3 and T4), Synthesis

• The thyroid gland is a butterfly-shaped gland located in the neck.
• The hormones T3 and T4 are produced in the follicles.
• T4 is the major product; T3 is more active.
• Steps in T3 and T4 synthesis involve:
  1. Thyroglobulin synthesis and secretion into follicles.
  2. Iodide trapping.
  3. Iodide oxidation and organification.
  4. Coupling of MIT and DIT to form T3 and T4.
  5. Colloid endocytosis.
  6. Proteolytic cleavage and release of T3 and T4.
• Transport of T3 and T4 in the blood is mostly through binding to TBG (thyroxin-binding globulin) and albumin.

Regulation of Thyroid Hormone Secretion

• TRH ("thyrotropin-releasing hormone") from the hypothalamus stimulates TSH ("thyroid-stimulating hormone") release from the anterior pituitary.
• TSH stimulates T3 and T4 release from the thyroid gland.
• High levels of T3 and T4 exert negative feedback on the hypothalamus and anterior pituitary, suppressing TRH and TSH release.
• Iodine is crucial for thyroid hormone synthesis.

Thyroid Hormone Actions

• Metabolism
• CNS function
• Growth and development
• Other effects

Diseases of the Thyroid

• Hyperthyroidism (overactive thyroid):
  • Graves' disease (most common cause).
  • Increased thyroid hormone production → hypermetabolism.
• Hypothyroidism (underactive thyroid):
  • Iodine deficiency or autoimmune thyroiditis.
  • Decreased thyroid hormone production → hypometabolism.

Parathyroid Gland and Calcium Homeostasis

• The parathyroid glands regulate calcium levels.
• The parathyroid gland secretes parathyroid hormone (PTH).
• PTH increases serum calcium, mostly by increasing bone resorption.
• Calcitonin decreases serum calcium, mostly by reducing bone resorption.
• Vitamin D is influenced by PTH and plays an important role in increasing intestinal calcium absorption.

Calcium

• Key roles:
  1. Bone structure
  2. Neuromuscular excitability
  3. Hormonal secretion
  4. Enzymatic regulation
  5. Blood coagulation
  6. Second messengers
• Regulating plasma calcium levels is vital for proper bodily functions.

Calcium Metabolism

• Calcium absorption, excretion, and bone deposition.
• A balance between calcium absorption from food and excretion by the kidneys and bone maintain the concentration.

Regulation of Calcium

• Non-hormonal regulation is critical for short-term calcium maintenance.
• Hormonal regulation (Vitamin D, PTH, and Calcitonin) provides long-term regulation of calcium and phosphate blood concentration.

Parathyroid Hormone (PTH)

• Source: secreted by chief (principal) cells in the parathyroid glands.
• Stimulus: low plasma calcium.
• Mechanism of action: influences bone, kidney, and the intestine to raise plasma calcium.
• Functions of PTH: stimulates bone resorption, increases calcium reabsorption in the kidneys, enhances vitamin D activation, and stimulates phosphate excretion.

Calcitonin

• Source: secreted by parafollicular cells (C cells) of the thyroid gland.
• Stimulus: high plasma calcium levels.
• Mechanism of action: reduces plasma calcium levels.
• Functions: inhibits bone resorption and increases calcium excretion by the kidneys.

Vitamin D

• Precursor hormone, synthesized in the skin or intake from food.
• Converted to its active form in liver and kidney.
• Activated form (calcitriol) promotes calcium absorption from the intestine, increases bone resorption, and enhances phosphate absorption from the gut.

Adrenocortical Hormones (Cortisol)

• Synthesized from cholesterol in the adrenal cortex.
• Primary function is to regulate metabolism in response to stress.
  • Carbohydrate metabolism: increases blood glucose levels through gluconeogenesis.
  • Protein metabolism: breaks down proteins into amino acids.
  • Lipid metabolism: mobilizes fatty acids from adipose tissue.
• Important role during stress response, suppressing the immune system and maintaining blood pressure.

Regulation of Glucocorticoid Secretion

• Hypothalamus's corticotropin-releasing factor (CRH) → anterior pituitary's ACTH ("adrenocorticotropic hormone") secretion.
• ACTH induces glucocorticoid release from the adrenal cortex.
• A negative feedback mechanism by cortisol prevents further CRH and ACTH secretion.

Cushing's Syndrome

• Caused by prolonged exposure to excessive glucocorticoid levels.
• Causes include pituitary adenomas producing excessive ACTH, adrenal tumors, or exogenous glucocorticoid intake.
• Leads to a complex set of metabolic, immune, and systemic abnormalities.

Physiology of Pancreas and Insulin

• The pancreas is a glandular organ that produces digestive enzymes (exocrine function) and hormones (endocrine function).
• Endocrine function is conducted by pancreatic islets:
  • Beta cells secrete insulin.
  • Alpha cells secrete glucagon.
  • Delta cells secrete somatostatin.
• Insulin decreases blood glucose levels by promoting glucose uptake into cells, glycogen synthesis in liver and skeletal muscle, and fat synthesis in adipose tissue.
• Glucagon increases blood glucose levels by stimulating glycogenolysis in the liver and gluconeogenesis.

Blood Glucose Regulation

• Factors increasing blood glucose usually diminish insulin secretion, and factors decreasing blood glucose elevate insulin secretion.
• In response to high blood glucose, beta cells in the pancreatic islets release insulin, which lowers blood glucose levels by facilitating glucose uptake in muscle and fat tissue and promoting glycogen synthesis in the liver.
• In response to low blood glucose, alpha cells of the pancreatic islets release glucagon, which raises blood glucose by stimulating glycogenolysis in the liver and gluconeogenesis.

Diabetes Mellitus

• Two types: Type 1 (autoimmune attack of β cells) and Type 2 (resistance to insulin).
• Characterizing symptoms include polyuria, polydipsia, and polyphagia.
• Type 1 requires insulin injections; Type 2 often managed with lifestyle modifications and/or oral agents.

Pituitary Gland

• Consists of two parts:
  • Anterior pituitary: produces various hormones that regulate other glands (adenohypophysis).
  • Posterior pituitary: stores and releases hormones produced by the hypothalamus ((neurohypophysis)) (ADH, Oxytocin).
• Six anterior pituitary hormones have important roles:
  1. Growth hormone (GH)
  2. Prolactin (PRL)
  3. Adrenocorticotropic hormone (ACTH).
  4. Thyroid-stimulating hormone (TSH)
  5. Follicle-stimulating hormone (FSH)
  6. Luteinizing hormone (LH)

This quiz explores the intricacies of the endocrine system and its functions. Understand how various glands and hormones regulate key processes such as growth, metabolism, and reproductive functions. Test your knowledge on end organ roles, hormone secretion, and homeostasis.