Pancreatic Hormones and Clinical Manifestations Quiz

Hormone Receptors and Action

• Hormone receptors are located on the plasma membrane, mitochondria, other organelles, or in the nucleus
• There are thousands of receptors for a given hormone, which binding turns metabolic pathways on or off
• Hydrophobic hormones (e.g. Estrogen, T3, Aldosterone) penetrate the plasma membrane and bind to intracellular receptors
• Hydrophilic hormones (e.g. Epinephrine) must bind to cell surface receptors

Thyroid Hormone Effects

• Thyroid hormone (TH) binds to receptors on:
  • Mitochondria: increases rate of aerobic respiration
  • Ribosomes and chromatin: stimulates protein synthesis
  • Na+-K+ ATPase: generates heat

Hydrophilic Hormones: Mode of Action

• cAMP as a second messenger:
  1. Hormone binding activates G(s) protein
  2. Activates adenylate cyclase
  3. Produces cAMP
  4. Activates kinases
  5. Activates enzymes
  6. Metabolic reactions: synthesis, secretion, and change in membrane potentials
• Other second messengers:
  • G-coupled proteins: may use different second messengers in different tissues
  • Examples: alpha 1, alpha 2, IP3, DAG, PKC, calmodulin, MLCK, and myosin

Endocrine System Overview

• Hormones: chemical messengers secreted into the bloodstream, stimulating a response in another tissue or organ
• Target cells: have receptors for the hormone
• Endocrine glands: produce hormones
• Endocrine system: includes endocrine organs (e.g. thyroid, pineal), hormone-producing cells in organs (e.g. brain, heart, small intestine)

Endocrine vs. Exocrine Glands

• Endocrine glands: secrete products directly into the bloodstream, no ducts
• Exocrine glands: secrete products through a duct and onto an open surface or organ cavity

Pancreas

• Both an exocrine and endocrine gland
• Endocrine tissue: clusters of endocrine cells called "Islets of Langerhans"
• Four types of cells that secrete different hormones:
  • Alpha (α) cells: glucagon
  • Beta (β) cells: insulin
  • Delta (δ) cells: somatostatin
  • F cells: pancreatic polypeptide

Pancreatic Hormones

• Insulin:
  • Secreted after a meal with carbohydrates that raise glucose blood levels
  • Stimulates glucose and amino acid uptake
  • Promotes nutrient storage effect (promotes glycogenesis and lipogenesis)
  • Antagonizes glucagon
• Glucagon:
  • Secreted when blood glucose is low
  • Acts on liver cells to release glycogen
  • Increases blood sugar
  • Stimulates glycogenolysis, fat catabolism, and promotes absorption of amino acids for gluconeogenesis
• Somatostatin:
  • Secreted with a rise in blood glucose and amino acids after a meal
  • Inhibits GH secretion
  • Paracrine secretion: inhibits secretion of insulin and glucagon by α and β cells

Endocrine Functions of Other Organs

• Heart: atrial natriuretic peptide released with an increase in blood pressure
• Skin: helps produce vitamin D3
• Liver:
  • 15% of erythropoietin (stimulates bone marrow)
  • Angiotensinogen (a prohormone) precursor of angiotensin II
  • Source of IGF-I (works with GH)
  • Converts vitamin D3 to calcidiol
  • Hepcidin: inhibits intestinal absorption of iron into the bloodstream
• Kidneys:
  • Produces 85% of erythropoietin
  • Renin converts angiotensinogen to angiotensin I
  • Converts calcidiol to calcitriol (active form of vitamin D)
• Stomach and small intestines: 10 enteric hormones coordinate digestive motility and secretion
• Placenta: secretes estrogen, progesterone, and others regulate pregnancy, stimulate development of the fetus and mammary glands

Hormone Synthesis

• Steroid hormones: synthesized from cholesterol
• Peptides and glycoproteins: synthesized in the RER, further modified in the Golgi complex
• Monoamines: synthesized from tyrosine (except melatonin, which is synthesized from tryptophan)

Hormone Transport

• Hydrophilic hormones: transported in the bloodstream, unbound, and water-soluble
• Steroid hormones: must bind to transport proteins for transport, prolonging half-life
• Transport proteins in blood plasma: albumin, thyroxine-binding globulin (TGB), and transcortin

Adrenal Gland

• Cortex: three zones, each producing different hormones
  • Zona glomerulosa: mineralocorticoids (e.g. aldosterone)
  • Zona fasciculata: glucocorticoids (e.g. cortisol)
  • Zona reticularis: sex hormones (e.g. androgens and estrogens)
• Medulla: chromaffin cells producing catecholamines (e.g. epinephrine and norepinephrine)

Stress and Adaptation

• General adaptation syndrome: the body's response to stress
• Three stages:
  1. Alarm reaction
  2. Stage of resistance
  3. Stage of exhaustion

Paracrine Secretions

• Chemical messengers that diffuse short distances and stimulate nearby cells
• Examples:
  • Histamine from mast cells in connective tissue
  • Nitric oxide from endothelium of blood vessels
  • Somatostatin from delta cells
  • Catecholamines from adrenal medulla

Eicosanoids

• Paracrine secretions derived from arachidonic acid
• Examples:
  • Leukotrienes: mediate allergic and inflammatory reactions
  • Prostacyclin: inhibits blood clotting and vasoconstriction
  • Thromboxanes: stimulate vasoconstriction and clotting
  • Prostaglandins: diverse effects, including relaxation of smooth muscle and stimulation of relaxation of blood vessels

Endocrine Disorders

• Too much or too little hormone

• Variations in hormone concentration and target cell sensitivity

• Examples:

  • Hyposecretion: inadequate hormone release
  • Hypersecretion: excessive hormone release
  • Pituitary disorders: hypersecretion of growth hormones
  • Thyroid gland disorders: congenital hypothyroidism, endemic goiter, toxic goiter, and hypothyroidism### Hormone Synthesis and Transport

• Insulin formation: preproinsulin is converted to proinsulin in the RER, and then split into insulin and C peptide in the Golgi complex.

• Monoamine synthesis: all are synthesized from tyrosine, except melatonin, which is synthesized from tryptophan.

• Thyroid hormone synthesis: composed of two tyrosine molecules, requires a mineral, iodine.

• T3 and T4 synthesis: follicular cells absorb I- from blood, store in lumen as I-, synthesize thyroglobulin, and store in lumen containing tyrosine.

• TSH stimulates follicular cells to remove T3 and T4 from thyroglobulin for release into plasma.

• Hormone transport: monoamines and peptides are hydrophilic, transported in the bloodstream as a water-soluble form.

• Steroids and thyroid hormone are hydrophobic, must bind to transport proteins for transport.

Endocrine System Overview

• Hypothalamus and pituitary gland: other endocrine glands, hormones, and their actions.
• Stress and adaptation: eicosanoids and paracrine signaling.
• Endocrine disorders: too much or too little hormone.

Endocrine System Components

• Hormone: a chemical messenger secreted into the bloodstream, stimulating a response in another tissue or organ.
• Target cells: have receptors for the hormone.
• Endocrine glands: produce hormones.
• Endocrine system: endocrine organs, hormone-producing cells in organs.

Endocrine vs. Exocrine Glands

• Exocrine glands: secrete their products through a duct and onto an open surface or organ cavity.
• Endocrine glands: secrete their products directly into the bloodstream, no ducts.

Nervous vs. Endocrine System

• Endocrine system: endocrine organs, hormone-producing cells in organs.
• Nervous system: brain, spinal cord, and peripheral nerves.

Pancreas

• Is both exocrine and endocrine.
• Endocrine tissue: clusters of endocrine cells called "Islets of Langerhans".
• Islets include 4 types of cells that secrete different hormones:
  • Alpha (a) cells: glucagon.
  • Beta (b) cells: insulin.
  • Delta (d) cells: somatostatin.
  • F cells: pancreatic polypeptide.

Pancreatic Hormones

• Insulin: secreted after a meal, stimulates glucose and amino acid uptake, and nutrient storage.
• Glucagon: secreted when blood glucose is low, acts on liver cells to release glycogen, and increases blood sugar.
• Somatostatin: secreted with a rise in blood glucose and amino acids, inhibits GH, and paracrine secretion inhibits insulin and glucagon.

Endocrine Functions of Other Organs

• Heart: atrial natriuretic peptide, released with an increase in BP.
• Skin: helps produce D3.
• Liver: 15% of erythropoietin, angiotensinogen, and IGF-I.
• Kidneys: 85% of erythropoietin, renin, and calcidiol.
• Stomach and small intestines: 10 enteric hormones, coordinate digestive motility and secretion.
• Placenta: secretes estrogen, progesterone, and others, regulates pregnancy, and stimulates development of the fetus and mammary glands.

Hormone Classification

• Fat-soluble: steroids, derived from cholesterol.
• Water-soluble: peptides and glycoproteins, and monoamines.
• Steroids: sex steroids, corticosteroids, and calcitriol.
• Peptides and glycoproteins: OT, ADH, and most of the anterior pituitary hormones.
• Monoamines: catecholamines, and thyroid hormones.

Oxytocin and ADH

• Oxytocin: causes uterine contractions and milk ejection.
• ADH: targets kidneys, increases water retention, and reduces urine.

Growth Hormone and Aging

• Childhood and adolescence: bone, cartilage, and muscle growth.
• Adulthood: increase osteoblastic activity, and appositional growth affecting bone thickening and remodeling.
• Blood concentration: higher during deep sleep, after high protein meals, and after vigorous exercise.

Posterior Pituitary Hormones

• ADH: targets kidneys, increases water retention, and reduces urine.
• Oxytocin: causes uterine contractions and milk ejection.

Pineal Gland

• Produces serotonin by day, and converts it to melatonin at night.
• Melatonin: suppresses in SAD, and increases in PMS.

Thymus

• Located in the mediastinum, superior to the heart.
• Involution after puberty.
• Secretes hormones that regulate development and later activation of T-lymphocytes.

Thyroid Gland

• Anatomy: largest endocrine gland, high rate of blood flow.
• Thyroid hormones: T3 and T4, produced by thyroid follicles, and stimulate the body's metabolic rate.

Parathyroid Glands

• Produce parathyroid hormone, which increases blood Ca2+ levels.

Adrenal Gland

• Adrenal cortex: produces corticosteroids, and adrenaline.
• Adrenal medulla: produces catecholamines.

Adrenal Cortex

• Zona glomerulosa: produces mineralocorticoids, and aldosterone.
• Zona fasciculata: produces glucocorticoids, and cortisol.
• Zona reticularis: produces sex hormones.

Adrenal Medulla

• Produces catecholamines, and stimulates the sympathetic nervous system.
• Increases alertness, anxiety, or fear.

Endocrine Disorders

• Hyposecretion: inadequate hormone release, leading to various disorders such as diabetes insipidus, and thyrotoxicosis.
• Hypersecretion: excessive hormone release, leading to various disorders such as acromegaly, and Cushing's syndrome.

Endocrine Disorders

• Thyroid gland disorders: congenital hypothyroidism, myxedema, endemic goiter, toxic goiter, and hyperthyroidism.
• Parathyroid disorders: hypoparathyroidism, and hyperparathyroidism.
• Adrenal disorders: Cushing's syndrome, and adrenogenital syndrome.
• Diabetes mellitus: signs and symptoms, types, and pathology.
• Hyperinsulinism: causes, and symptoms.

Endocrine System Pathology

• Acute pathology: cells cannot absorb glucose, rely on fat and proteins.
• Chronic pathology: chronic hyperglycemia leads to neuropathy, and cardiovascular damage.### Communication in Nervous and Endocrine Systems
• Nervous system uses both electrical and chemical signals, while endocrine system uses only chemical signals
• Nervous system reacts quickly (1-10 msec) and stops quickly, while endocrine system reacts slowly (seconds or days) and effects may persist for weeks
• Nervous system adapts quickly to long-term stimuli, while endocrine system response persists
• Nervous system has targeted and specific effects on one organ, while endocrine system has general and widespread effects on many organs

Overlapping Functions

• Some chemicals function as both hormones and neurotransmitters (NE, cholecystokinin, thyrotropin-releasing hormone, dopamine, and ADH)
• Some hormones are secreted by neuroendocrine cells (neurons) like oxytocin and catecholamines
• Both systems have overlapping effects on same target cells (NE and glucagon cause glycogenolysis in liver)
• Systems can regulate each other (neurons can trigger hormone secretion, and hormones can stimulate or inhibit neurons)

Hypothalamus and Pituitary Gland

Hypothalamus

• Regulates homeostasis mechanisms and some endocrine functions
• Shaped like a flattened funnel and forms floor and walls of third ventricle

Pituitary Gland

• Suspended from hypothalamus by stalk (infundibulum) and housed in sella turcica of sphenoid bone
• Diameter of 1.3 cm
• Anterior pituitary (adenohypophysis) arises from hypophyseal pouch (outgrowth of pharynx)
• Posterior pituitary (neurohypophysis) arises from brain

Embryonic Development and Histology of Pituitary Gland

Pituitary Gland Anatomy and Hormones

• Anterior pituitary hormones: FSH, LH, TSH, ACTH, PRL, and GH
• Posterior pituitary hormones: oxytocin and ADH

Control of Pituitary

• Anterior lobe control: releasing hormones and inhibiting hormones of hypothalamus
• Posterior lobe control: neuroendocrine reflexes (hormone release in response to nervous system signals)

Feedback from Target Organs

• Negative feedback: target organ hormone levels inhibit release of tropic hormones
• Positive feedback: stretching of uterus triggers OT release, causing more contraction and stretching of uterus, until delivery

Pituitary Hormones - Anterior Lobe

• Tropic hormones target other endocrine glands
• FSH targets gonads
• LH mainly stimulates hormone production in females and testosterone secretion in males
• TSH stimulates growth of thyroid and secretion of thyroid hormones
• ACTH regulates response to stress and stimulates adrenal cortex to secrete corticosteroids
• PRL stimulates milk synthesis in females and LH sensitivity and testosterone secretion in males
• GH (growth hormone) affects growth and metabolism

Hormone Receptors

• Located on plasma membrane, mitochondria, other organelles, or in nucleus
• Thousands of receptors for a given hormone, binding turns metabolic pathways on or off

Hormone Mode of Action

• Hydrophobic hormones (estrogen, T3, aldosterone) penetrate plasma membrane and bind to intracellular receptors
• Hydrophilic hormones (epinephrine) bind to cell surface receptors

Thyroid Hormone Effects

• TH binds to receptors on mitochondria, increasing rate of aerobic respiration
• TH binds to receptors on ribosomes and chromatin, increasing protein synthesis
• TH stimulates production of Na+-K+ ATPase, generating heat

Hydrophilic Hormones: Mode of Action

• Use cAMP as a second messenger (epinephrine)
• Hormone binding activates G(s) protein, which activates adenylate cyclase, producing cAMP
• cAMP activates kinases, which activate enzymes, leading to metabolic reactions

Hydrophilic Hormones: Mode of Action (Cont.)

• Other second messengers: G-coupled proteins, alpha 1 and alpha 2
• Alpha 1 uses Gq, PLC, PIP2, DAG, PKC, and IP3
• Alpha 2 uses Gi, inhibiting adenylate cyclase, decreasing cAMP and PKA

Test your knowledge on pancreatic hormones and clinical manifestations related to catecholamines secretion. Learn about the functions of different types of cells in the endocrine tissue of the pancreas.