Endocrine System and Hormone Function

• The endocrine system maintains homeostasis by secreting hormones that regulate bodily functions, including metabolism, growth, development, reproduction, and responses to stress and environmental changes.
• Hormones are chemical messengers from endocrine glands that travel through the bloodstream to target tissues.
• Hormones act on cells by:
  • Binding to cell surface receptors
  • Diffusing through the plasma membrane to bind intracellular receptors
  • Altering gene expression
• Hormone effects on a cell depend on the presence of specific receptors.
• Half-life is the time it takes for a hormone's blood concentration to decrease by half.
• Hormone action must be terminated to prevent overstimulation and maintain homeostasis.

Endocrine vs. Nervous Systems

• Endocrine: Uses hormones, slow-acting, long-lasting effects, regulates metabolic and long-term changes.
• Nervous: Uses electrical/chemical signals, rapid-acting, short-lasting effects, controls immediate and short-term changes.

Hormone Categories

• Peptide/protein hormones: Chains of amino acids.

• Steroid hormones: Derived from cholesterol, lipid-soluble.

• Amino acid-derived hormones: Made from tyrosine or tryptophan.

• Negative feedback prevents hormone overproduction by reducing hormone synthesis when levels are high.

• Positive feedback amplifies hormone production in specific situations, such as childbirth.

Peptide Hormone Synthesis

• Synthesized in the rough endoplasmic reticulum and packaged in the Golgi apparatus.
• A prohormone is a precursor molecule cleaved to form the active hormone.
• Peptide hormones cannot enter target cells because they are too large and water-soluble to pass through the cell membrane.
• A ligand is a molecule that binds to a specific receptor.
• A hormone receptor is a protein molecule on or in a target cell that specifically binds to a hormone.
• Steroid hormones are synthesized from cholesterol in the smooth endoplasmic reticulum and have a four-ring structure.
• Steroid hormones are transported in the blood bound to carrier proteins because they are lipid-soluble.
• Steroid hormones pass through the cell membrane and bind to intracellular receptors, unlike peptide hormones.
• Amino-acid derived hormones are made from tyrosine and tryptophan.
• Thyroid hormones (T3 and T4) are amino-acid derived hormones that are not water-soluble.
• G-protein coupled cascades/second messenger cascades/signal transduction pathways transmit signals from outside the cell to inside, often amplifying the signal.

G Protein Coupled Signal Transduction Pathway (Adenylyl Cyclase)

• Hormone binds to G protein-coupled receptor.

• G protein is activated.

• G protein activates adenylyl cyclase.

• Adenylyl cyclase produces cAMP.

• cAMP activates protein kinase A.

• Protein kinase A phosphorylates target proteins.

• Phosphorylation is the addition of a phosphate group to activate or deactivate enzymes.

G Protein Coupled Signal Transduction Pathway (Phospholipase)

• Hormone binds to receptor.

• G protein is activated.

• G protein activates phospholipase C.

• Phospholipase C cleaves PIP2 into DAG and IP3.

• IP3 releases calcium from ER.

• Calcium and DAG activate protein kinase C.

• Second messengers relay signals from receptors to target molecules inside a cell; third messengers are activated by second messengers.

• Signal amplification occurs because each step activates multiple molecules of the next step.

• Steroid hormones bind to intracellular receptors, and the complex binds to DNA to alter gene expression.

• Up-regulation increases receptors in response to low hormone levels; down-regulation decreases receptors in response to high hormone levels.

• Releasing and inhibiting hormones are made in the hypothalamus and control anterior pituitary hormones.

• The anterior pituitary is glandular tissue; the posterior pituitary is neural tissue.

• The hypothalamus connects to the pituitary via the infundibulum and the hypophyseal portal system.

• The hypothalamo-hypophyseal portal system connects the hypothalamus to the anterior pituitary.

• The anterior pituitary secretes tropic hormones including TSH, ACTH, GH, FSH, LH, and PRL.

• Releasing hormones from the hypothalamus signal the anterior pituitary to secrete tropic hormones.

• Anterior pituitary hormones stimulate other endocrine glands.

Hormone Connections

• TRH (hypothalamus) → TSH (anterior pituitary) → T3 and T4 (thyroid gland)

• CRH (hypothalamus) → ACTH (anterior pituitary) → Cortisol (adrenal cortex)

• GHRH (hypothalamus) → GH (anterior pituitary) → IGFs (liver and other tissues)

• GnRH (hypothalamus) → FSH and LH (anterior pituitary) → Sex hormones (gonads)

• PRH (hypothalamus) → Prolactin (anterior pituitary) → Acts on mammary glands

• Prolactin stimulates milk production.

• Adrenal cortex produces steroid hormones; adrenal medulla produces catecholamines.

Adrenal Cortex Zones

• Zona glomerulosa: Aldosterone

• Zona fasciculata: Cortisol

• Zona reticularis: Androgens

• The adrenal medulla makes epinephrine and norepinephrine and is innervated by preganglionic sympathetic neurons.

• Cortisol is synthesized on demand due to ACTH stimulation and cannot be stored.

• Almost all cells have cortisol receptors.

• Cortisol increases glucose availability and suppresses immune function.

• Cellular response to cortisol can take hours, while negative feedback can occur within minutes.

• High cortisol inhibits CRH from the hypothalamus and ACTH from the anterior pituitary.

• Cortisol increases blood glucose, suppresses immune function, and helps the body respond to stress.

Cushing Syndrome

• Prolonged exposure to high cortisol levels.
• Causes include pituitary tumors (Cushing's disease), adrenal tumors, or long-term glucocorticoid use.
• Symptoms: weight gain, thin skin, easy bruising, muscle weakness, mood changes, high blood pressure and diabetes.
• Treatment may involve surgery, radiation, or medication to reduce cortisol levels.

Addison's Disease

• Adrenal glands don't produce enough cortisol and aldosterone.

• Most common cause is autoimmune destruction of the adrenal cortex.

• Symptoms: fatigue, muscle weakness, weight loss, low blood pressure, salt cravings, and hyperpigmentation.

• Treatment: Lifelong hormone replacement therapy.

• Thyroid hormones regulate metabolism, growth, and development.

• Thyroid hormones are produced in the thyroid gland through iodination of tyrosine residues

• Iodide is essential for thyroid hormone production.

• T4 has four iodine atoms, T3 has three; T3 is more potent but present in smaller amounts.

• Thyroid hormones are critical for normal growth and development in children especially of the nervous system.

• Iodine deficiency → Low thyroid hormone production → Increased TSH → Thyroid gland enlargement (goiter).

• High thyroid hormone levels inhibit TRH and TSH production as part of the thyroid hormone feedback loop.

• Growth hormone (GH) stimulates growth and cell reproduction and is most critical during childhood and adolescence.

• IGFs mediate many of the effects of growth hormone on target tissues.

• High GH or IGF levels inhibit GHRH and GH release within the GH feedback loop.

• Oxytocin and vasopressin (ADH) are secreted by the posterior pituitary and manufactured in the hypothalamus.

• Oxytocin stimulates uterine contractions and milk ejection; ADH regulates water reabsorption in the kidneys.

• Uterine contractions or suckling → More oxytocin release as part of the positive feedback loop.

• The posterior pituitary is made up of neural tissue.

• The hypothalamo-hypophyseal tract is a bundle of axons connecting the hypothalamus to the posterior pituitary.

• Insulin lowers blood glucose and is made in pancreatic beta cells.

• Glucagon raises blood glucose and is made in pancreatic alpha cells.

• Melatonin regulates sleep-wake cycles and is made in the pineal gland.

• Darkness → Stimulation of pineal gland → Melatonin production.

• Parathyroid hormone regulates calcium levels in the blood and is made in the parathyroid glands.

• Low blood calcium → PTH release → Increased calcium absorption, decreased calcium excretion, and bone resorption.

• Too much parathyroid hormone: Hypercalcemia, bone weakening.

• Not enough parathyroid hormone: Hypocalcemia, muscle spasms, tetany.

This content explores the endocrine system, focusing on hormone actions and effects. It covers topics like PTH secretion, feedback loops, pancreatic alpha cells, and sleep cycle regulation. The material also considers the role of the hypothalamus and hormone mechanisms in homeostasis.