Session 8: Endocrine System Part 2 - Detailed Notes

Thyroid Gland

• Butterfly-shaped gland in the anterior neck on the trachea, just inferior to the larynx.

• Consists of:

  • Isthmus: median mass connecting two lateral lobes.

• Follicular cells secrete thyroid hormone.

• Parafollicular cells secrete calcitonin.

• Colloid-filled follicles contain precursors to thyroid hormone.

Thyroid Hormone (TH)

• Body’s major metabolic hormone.

• Found in two forms:

  • T4 (thyroxine): major form with two tyrosine molecules and four bound iodine atoms.

  • T3 (triiodothyronine): form with two tyrosines with three bound iodine atoms.

• Must be converted to T3 at the tissue level.

• Both are iodine-containing amine hormones.

• Act like steroid hormones on target cells by binding to an intracellular receptor and moving to the nucleus.

Transport and Regulation

• T4 and T3 are transported by thyroxine-binding globulins (TBGs) - protein carrier

• T3 is 10 times more active than T4.

• Peripheral tissues have an enzyme to convert T4 to T3 (removes one iodine).

• TH release is regulated by negative feedback:

  • Falling TH levels stimulate the release of thyroid-stimulating hormone (TSH).

  • Rising TH levels provide negative feedback inhibition on TSH.

Major Functions

• Affects virtually every cell in the body.

• Enters target cell and binds to intracellular receptors within the nucleus, triggering the transcription of various metabolic genes.

  • Increases basal metabolic rate and heat production (calorigenic effect).

  • Regulates tissue growth and development.

    • Critical for normal skeletal and nervous system development and reproductive capabilities.

    • In adults, regulates nervous system reactivity.

  • Increases blood pressure.

Major Effects of Thyroid Hormone (T4 and T3)

• Increases basal metabolic rate and heat production
  • Referred to as calorigenic effect

• Regulates tissue growth and development

  Critical for normal skeletal and nervous system development and reproductive capabilities

• In the adult regulates nervous system reactivity

• Increases bloodpressure

  

Calcitonin

• Produced by parafollicular (C) cells in the thyroid gland in response to high Ca^{2+} levels.

• Antagonist to parathyroid hormone (PTH).

• Actions:

  • Inhibits osteoclast activity and prevents the release of Ca^{2+} from bone.

  • Stimulates Ca^{2+} uptake and incorporation into bone.

Parathyroid Gland

• Four to eight tiny yellow-brown glands embedded in the posterior aspect of the thyroid.

• Contain parathyroid cells that secrete parathyroid hormone (PTH).

• PTH is the most important hormone in Ca^{2+} homeostasis.

  • Secreted in response to low blood levels of Ca^{2+}.

  • Inhibited by rising levels of Ca^{2+}.

• Target organs are the skeleton, kidneys, and intestine.

Functions of Parathyroid Gland

• Stimulates osteoclasts to digest bone and release Ca^{2+} to the blood.

• Enhances reabsorption of Ca^{2+} by the kidneys.

• Promotes activation of vitamin D by kidneys, which leads to increased absorption of Ca^{2+} by intestinal mucosa.

Adrenal Glands

• Paired, pyramid-shaped organs atop the kidneys (suprarenal glands).

• Structurally and functionally, two glands in one:

  • Adrenal cortex: three layers of glandular tissue that synthesize and secrete several different hormones.

  • Adrenal medulla: nervous tissue that is part of the sympathetic nervous system.

Mineralocorticoids

• Regulate electrolyte concentrations (primarily Na^{+} and K^{+}) in ECF.

  • Importance of Na^{+}: affects ECF volume, blood volume, and blood pressure.

  • Importance of K^{+}: sets resting membrane potential of cells.

Aldosterone

• Most potent mineralocorticoid.

• Stimulates Na^{+} reabsorption by kidneys.

• Stimulates K^{+} elimination by kidneys.

• Primary factors that regulate aldosterone secretion:

  • Renin-angiotensin-aldosterone mechanism.

  • Plasma concentration of K^{+}.

Regulation of Aldosterone Release

• Renin-angiotensin-aldosterone mechanism: Initiates cascade that produces angiotensin II.

  • Angiotensin II: Targets kidney tubules to increase the absorption of Na^{+} and increase secretion of aldosterone.

  • Absorption of Na^{+} and water causes increased K^{+} excretion, thereby increase blood volume and/or blood pressure.

• Plasma concentration of K^{+}: A direct stimulating effect on the Adrenal cortex (zona glomerulosa).

• Other Factors:

  • Adrenocorticotropic hormone (ACTH)

  • Atrial natriuretic peptide (ANP)

Glucocorticoids

• Influence the metabolism of most cells and help resist stressors.

• Keep blood glucose levels relatively constant.

• Maintain blood pressure by increasing the action of vasoconstrictors.

• Include:

  • Cortisol (hydrocortisone): the only glucocorticoid in significant amounts in humans.

  • Cortisone

  • Corticosterone

Cortisol - Regulation

• Cortisol is released in response to ACTH.

• ACTH is released in response to corticotropin-releasing hormone (CRH).

• CRH is released in response to low cortisol levels.

• Increased cortisol levels inhibit ACTH and CRH through negative feedback.

• Secretion cycles are governed by patterns of eating and activity.

• Acute stress (infection, physical or emotional trauma) interrupts cortisol rhythm.

Cortisol – Actions

• Causes an increase in blood levels of glucose, fatty acids, and amino acids.

• The prime metabolic effect is gluconeogenesis: the formation of glucose from fats and proteins by the liver.

  • Encourages cells to use fatty acids for fuel, so glucose is “saved” for the brain.

• Enhances vasoconstriction, causing a rise in blood pressure.

Glucocorticoids – Actions (Prolonged High Levels)

• Depress cartilage and bone formation (in kids).

• Inhibit inflammation by decreasing the release of inflammatory chemicals.

• Depress the immune system.

• Disrupt normal cardiovascular, neural, and gastrointestinal functions.

• Glucocorticoid drugs can control symptoms of many inflammatory diseases (arthritis, allergies) but can also cause undesirable effects.

Gonadocorticoids

• Weak androgens (male sex hormones) converted to testosterone in tissue cells.

  • Examples: androstenedione and dehydroepiandrosterone (DHEA).

• May contribute to:

  • Onset of puberty and appearance of secondary sex characteristics.

  • Sex drive in women.

  • Pubic & axillary hair growth.

  • Source of estrogens in postmenopausal women.

Adrenal Medulla

• Medullary chromaffin cells synthesize catecholamines:

  • Adrenaline (epinephrine) (80%).

  • Noradrenaline (norepinephrine) (20%).

• Effects of catecholamines:

  • Vasoconstriction.

  • Increased heart rate.

  • Increased blood glucose levels.

  • Blood diverted to the brain, heart, and skeletal muscle.

Adrenaline (Epinephrine) vs. Noradrenaline (Norepinephrine)

• Both hormones have basically the same effects, but:

  • Adrenaline (epinephrine) is more of a stimulator of metabolic activities.

    • Example: bronchial dilation and increased blood flow to skeletal muscles and the heart.

  • Noradrenaline has more of an influence on peripheral vasoconstriction and blood pressure.

• Responses to stressors are brief, unlike adrenal cortical hormones.

Short-Term Stress Response (Adrenal Medulla)

• Heart rate increases

• Blood pressure increases

• Bronchioles dilate

• The liver converts glycogen to glucose and releases glucose to the blood

• Blood flow changes, reducing digestive system activity and urine output

• Metabolic rate increases

Long-Term Stress Response (Adrenal Cortex)

• Kidneys retain sodium and water

• Blood volume and blood pressure rise

• Proteins and fats converted to glucose or broken down for energy

• Blood glucose increases

• Immune system suppressed

Summary of Adrenal Gland Hormones

• Mineralocorticoids (chiefly aldosterone)

  • Regulation of release: Stimulated by renin-angiotensin-aldosterone mechanism (activated by decreasing blood volume or blood pressure), elevated blood K^{+} levels, and ACTH (minor influence); inhibited by increased blood volume and pressure, and decreased blood K^{+} levels.

  • Target organ and effects: Kidneys: increase blood levels of Na^{+} and decrease blood levels of K^{+}; since water reabsorption usually accompanies sodium retention, blood volume and blood pressure rise.

• Glucocorticoids (chiefly cortisol)

  • Regulation of release: Stimulated by ACTH; inhibited by feedback inhibition exerted by cortisol.

  • Target organ and effects: Body cells: promote gluconeogenesis and hyperglycemia; mobilize fats for energy metabolism; stimulate protein catabolism; assist the body to resist stressors; depress inflammatory and immune responses.

• Gonadocorticoids (chiefly androgens, converted to testosterone or estrogens after release)

  • Regulation of release: Stimulated by ACTH; the mechanism of inhibition incompletely understood, but feedback inhibition not seen.

  • Target organ and effects: Insignificant effects in males; contributes to female libido; development of pubic and axillary hair in females; the source of estrogens after menopause.

• Catecholamines (epinephrine and norepinephrine)

  • Regulation of release: Stimulated by preganglionic fibers of the sympathetic nervous system.

  • Target organ and effects: Mimic sympathetic nervous system activation; increase heart rate and metabolic rate; increase blood pressure by promoting vasoconstriction.

Pancreas

• Triangular gland located partially behind the stomach.

• Has both exocrine and endocrine cells.

  • Acinar cells (exocrine) produce enzyme-rich juice for digestion.

  • Pancreatic islets (islets of Langerhans) contain endocrine cells:

    • Alpha (\alpha) cells produce glucagon (hyperglycemic hormone).

    • Beta (\beta) cells produce insulin (hypoglycemic hormone).

Pancreas - Insulin

• Secreted when blood glucose levels increase.

• Lowers blood glucose levels by:

  • Facilitating glucose uptake into cells.

  • Storing glucose as glycogen in the liver & skeletal muscle (glycogenesis).

  • Storing excess glucose and fatty acids as triglycerides in adipose tissue.

  • Inhibits breakdown of glycogen to glucose (glycogenolysis).

  • Storing amino acids as proteins in muscle.

  • Inhibits conversion of amino acids or fats to glucose (gluconeogenesis).

Regulation of Insulin Secretion

• Food intake and increased blood glucose concentration are the major controls.

  • Increased Gastrointestinal hormones (incretins)

  • Increased Blood amino acid concentration

  • Parasympathetic stimulation

  • All Factors increase Islet Beta cells to increase insulin secretion, to decrease blood glucose, blood fatty acids, blood amino acids.

    • Protein synthesis.

    • Fuel storage

  • Sympathetic stimulation (and epinephrine)

Pancreas – Glucagon

• Extremely potent hyperglycemic agent.

• Triggered by decreased blood glucose levels, rising amino acid levels, or sympathetic nervous system.

• Raises blood glucose levels by targeting the liver to:

  • Break down glycogen into glucose – Glycogenolysis.

  • Synthesize glucose from lactic acid and other non-carbohydrates – Gluconeogenesis.

  • Release glucose into the blood.

Insulin and Glucagon Regulation

• Insulin:

  • From Tissue cells, insulin stimulates glucose uptake by cells

  • Stimulates glycogen formation in the liver

  • Stimulus: Blood glucose level rises to normal range

• Glucagon:

  • Stimulates glycogen breakdown in the liver

  • Stimulus: Blood glucose level falls to normal range

Factors that Increase Blood Glucose

• Glucose absorption from the digestive tract.

• Hepatic glucose production:

  • Through glycogenolysis of stored glycogen.

  • Through gluconeogenesis.

Factors that Decrease Blood Glucose

• Transport of glucose into cells:

  • For utilization for energy production.

  • For storage.

    • As glycogen through glycogenesis.

    • As triglycerides.

• Urinary excretion of glucose (occurs only abnormally when the blood glucose level becomes so high it exceeds the reabsorptive capacity of kidney tubules during urine formation).

Gonads

• Produce the same steroid sex hormones as those of the adrenal cortex, just in lesser amounts.

Ovaries

• Produce estrogens and progesterone.

• Estrogen

  • Maturation of reproductive organs.

  • Menstrual cycle.

  • Appearance of secondary sexual characteristics.

• With progesterone, causes breast development and cyclic changes in the uterine mucosa.

Testes

• Produce testosterone.

  • Initiates maturation of male reproductive organs.

  • Causes the appearance of male secondary sexual characteristics and sex drive.

  • Necessary for normal sperm production.

  • Maintains reproductive organs in a functional state.

Hormone Secretion by Other Organs

• Heart

  • Atrial natriuretic peptide (ANP) decreases blood Na^{+} concentration, therefore blood pressure and blood volume.

• Kidneys

  • Erythropoietin signals the production of red blood cells.

  • Renin initiates the renin-angiotensin-aldosterone mechanism.

Actions at Target Site by Gland/Organ/ Tissue