Lecture 2 - Endocrine Physiology: Thyroid, Parathyroid, and Pancreas

1. Follicular cells – main function

• Closely packed follicular epithelial cells store and form thyroid hormones (T3, T4).

1. Parafollicular cells – main function

• Parafollicular (C‑cells) secrete calcitonin, lowering serum calcium by inhibiting osteoclasts and increasing renal excretion.

2. Effects of TSH on thyroid function

• Stimulates thyroid hormone synthesis, response of follicles, and release of T3/T4.

3. TSH – function & stimulation

• Promotes iodine/tyrosine coupling, thyroglobulin synthesis, and T3/T4 release.

3. T4/T3 – functions & stimulation

• Regulate gene activity, enzyme reactions, and multiple organ metabolic effects.

4. Steps of thyroid hormone synthesis

• Iodide ingestion and transport → iodination → MIT/DIT formation → coupling to T3/T4 → endocytosis → release to plasma with protein transport.

5. Hypothalamus–pituitary–thyroid feedback loop

• Secreted in circadian pattern

1. Islets of Langerhans – overall function

• Groups of endocrine cells that secrete hormones into blood; highly vascular; hormones reach liver first.

1. Alpha cells

• Secrete glucagon, increasing hepatic glucose output, glycogenolysis, and ketosis during fasting.

1. Beta cells

• Secrete insulin, promoting glucose uptake, glycogen storage, and inhibiting gluconeogenesis and lipolysis.

1. Delta cells

• Secrete somatostatin, inhibiting synthesis and secretion of peptide hormones.

1. F cells (PP cells)

• Secrete pancreatic polypeptide regulating GI motility, exocrine pancreatic secretion, and satiety.

2a. Insulin – stimulating factors, regulation, function

• Stimulated by glucose & GLP‑1; inhibited by catecholamines & somatostatin; promotes glucose uptake, glycogen storage, and inhibits hepatic glucose production.

2b. Amylin – stimulating factors, regulation, function

• Co‑secreted with insulin; slows gastric emptying and suppresses glucagon.

2c. Glucagon – stimulating factors, regulation, function

• Released with low glucose/insulin; promotes gluconeogenesis, glycogen access, and ketosis.

2d. Pancreatic somatostatin – stimulating factors, regulation, function

• Inhibits synthesis and secretion of peptide hormones;

2e. Gastrin – stimulating factors, regulation, function

• Aids digestion

2e. Ghrelin – stimulating factors, regulation, function

• Stimulates appetite;

2e. Pancreatic polypeptide – stimulating factors, regulation, function

• Released in response to meals; regulates GI motility, exocrine secretion, and satiety.

1. Relationship: parathyroid glands, PTH, PTH‑like hormone, calcium, magnesium, phosphorus

• Parathyroid cells sense calcium via CaSR; low calcium → ↑PTH; magnesium required for secretion; PTH and PTH‑related peptide regulate calcium/phosphorus.

2. Effects of PTH on kidneys

• Regulates calcium and phosphorus via renal reabsorption/excretion; kidney activates vitamin D under PTH stimulation.

2. Effects of PTH on bone

• Acts on bone to regulate calcium/phosphorus mobilization.

3. Relationship of PTH and vitamin D

• PTH stimulates kidney conversion of vitamin D to active 1,25‑OH₂‑D during low calcium/phosphorus, enabling calcium absorption and bone effects.

4. Feedback‑loop of the parathyroid gland

• Low ionized calcium increases PTH secretion; high calcium suppresses it via CaSR feedback.

Endocrine Physiology

• Study of hormone‑secreting organs including thyroid, parathyroid, and pancreas.

Thyroid Gland

• Endocrine gland in the neck producing T3/T4 for metabolism regulation.

Parathyroid Glands

• Small glands regulating calcium and phosphorus through PTH secretion.

Pancreas (Endocrine)

• Organ containing islets that secrete insulin, glucagon, somatostatin, and PP.

Follicular Cells

• Thyroid cells producing and storing T3/T4 precursors.

Parafollicular Cells (C‑cells)

• Thyroid cells releasing calcitonin to lower calcium.

Thyroid‑Stimulating Hormone (TSH)

• Pituitary hormone stimulating thyroid growth and T3/T4 release.

Thyrotropin‑Releasing Hormone (TRH)

• Hypothalamic hormone stimulating TSH secretion.

T4 (Thyroxine)

• Thyroid hormone controlling metabolism and converted to T3.

T3 (Triiodothyronine)

• Active thyroid hormone regulating cellular metabolic activity.

Thyroid Hormone Synthesis

• Iodine uptake, iodination of tyrosine, coupling (MIT/DIT), and hormone release.

Thyroid Feedback Loop

• Hypothalamus → TRH → TSH → T3/T4; high hormone levels suppress TRH/TSH.

Parathyroid Hormone (PTH)

• Hormone increasing calcium by acting on bone, kidney, and intestine.

Serum Calcium Regulation

• PTH adjusts calcium, magnesium, and phosphorus levels.

PTH & Kidneys

• Increases calcium reabsorption and activates vitamin D.

PTH & Bone

• Stimulates osteoclasts to release calcium.

Parathyroid Feedback Loop

• Low calcium increases PTH; high calcium suppresses it.

Islets of Langerhans

• Pancreatic clusters releasing insulin, glucagon, somatostatin, and PP.

Alpha Cells

• Secrete glucagon to raise blood glucose.

Beta Cells

• Secrete insulin to lower blood glucose.

Delta Cells

• Release somatostatin to inhibit hormone secretion.

F Cells (PP Cells)

• Produce pancreatic polypeptide regulating GI motility and secretions.

Insulin

• Hormone promoting glucose uptake and storage.

Amylin

• Co‑secreted with insulin; slows gastric emptying and suppresses glucagon.

Glucagon

• Raises glucose via glycogen breakdown and gluconeogenesis.

Pancreatic Somatostatin

• Inhibits pancreatic endocrine activity.

Gastrin

• Stimulates gastric acid secretion.

Ghrelin

• Hormone increasing appetite.

Pancreatic Polypeptide (PP)

• Regulates GI motility, pancreatic exocrine output, and satiety.

Thyroid Anatomy

• Two lobes and isthmus; highly vascular gland.

Parathyroid Anatomy

• Four small glands near thyroid; sometimes ectopic.

Recurrent Laryngeal Nerve

• Nerve near thyroid at risk during surgery.

Thyroid Histology

• Follicles with epithelial cells storing thyroid hormone.

Chief Cells

• Parathyroid cells producing PTH.

Clear Cells

• Parathyroid cells containing glycogen.

Oxyphil Cells

• Larger parathyroid cells with uncertain function.

Iodine Metabolism

• Dietary iodine converted to iodide and transported to thyroid.

MIT & DIT

• Tyrosine derivatives forming T3 and T4.

Thyroglobulin

• Protein scaffold for thyroid hormone synthesis.

TBG (Thyroxine‑Binding Globulin)

• Main transport protein carrying T3/T4 in blood.

Thyroid Hormone Circadian Secretion

• Daily rhythmic release pattern controlled by hypothalamus.

Thyroid Receptor (TR)

• Intracellular receptor binding T3 to regulate gene expression.

Thyroid Effects: Heart

• Increases β‑adrenergic receptor activity and catecholamine response.

Thyroid Effects: Lung

• Maintains hypoxia and hypercapnia responses.

Thyroid Effects: Adipose

• Stimulates lipolysis.

Thyroid Effects: Gut

• Increases carbohydrate absorption and GI motility.

Parathyroid Physiology

• Regulates calcium and phosphorus via PTH secretion.

Calcium‑Sensing Receptor (CaSR)

• Receptor detecting serum calcium to adjust PTH release.

PTH Regulation

• Low calcium increases PTH; high calcium suppresses it.

PTH Actions

• Acts on kidney, bone, and GI tract to raise calcium.

Magnesium & PTH

• Magnesium required for healthy PTH secretion.

Calcium

• Mostly in bones; essential for muscle contraction, secretion, and clotting.

Albumin‑Bound Calcium

• Fraction of calcium attached to albumin in blood.

Phosphorus

• Mineral crucial for energy, bone formation, membranes, and DNA.

Calcium–Phosphorus Metabolism

• Regulated by PTH, PTH‑related peptide, vitamin D, bone, and magnesium.

Kidney Role

• Reabsorbs or excretes calcium/phosphate and activates vitamin D.

Small Intestine Role

• Adjusts dietary calcium absorption.

Parafollicular Cells (C‑cells)

• Release calcitonin to lower calcium.

Vitamin D Source

• Primarily from sunlight; diet provides smaller amounts.

Vitamin D Activation

• Liver makes 25‑OH‑D; kidney makes active 1,25‑OH₂‑D.

PTH & Vitamin D

• Low calcium/phosphate increases PTH, stimulating vitamin D activation.

Vitamin D Target Organs

• Acts on intestine and bone to support calcium absorption and remodeling.

Calcitonin

• Hormone lowering calcium when levels are high.

Calcitonin & Bone

• Inhibits osteoclasts to prevent calcium/phosphate release.

Calcitonin & Kidney

• Increases urinary calcium and phosphate excretion.

PTH‑Related Peptide (PTHrP)

• Mimics PTH effects; involved in development.

PTHrP in Malignancy

• Tumors may produce it, causing hypercalcemia.

Islets of Langerhans (Slide 23)

• Pancreatic clusters containing alpha, beta, delta, and PP cells.

Alpha Cells

• Secrete glucagon to raise blood glucose.

Beta Cells

• Release insulin to lower glucose and promote storage.

Delta Cells

• Produce somatostatin to inhibit hormone secretion.

PP Cells

• Release pancreatic polypeptide to regulate GI motility and secretions.

Islet Blood Flow

• Highly vascular; hormones reach liver before systemic circulation.

Fasting State (Slide 24)

• Glucagon increases glucose output, glycogen breakdown, and ketosis.

Fed State

• Insulin decreases hepatic glucose production and promotes glycogen storage.

Stress State

• Glucagon, epinephrine, and cortisol elevate glucose for brain/CNS.