2 .Thyroid Gland• located anteriorly in cervical region, just inferior to

thyroid cartilage; two lobes connected by thin isthmus

• largest purely endocrine gland in body

• consists of follicles (cuboidal or simple squamous epithelium) filled with colloid (combination of protein [thyroglobulin] containing amino acid tyrosine [building block of thyroid hormones])

• parafollicular cells produce calcitonin

http://www.usc.edu/hsc/dental/ghisto/end/c_26.html

2. Thyroid Gland: T4 and T3

• hormones based on amino acid tyrosine (differ in number of iodine ions)

– thyroxine (tetraiodothyronine [T4]) and

– triiodothyronine (T3)

• T3 is 10x more active, but less common (T4 accounts for about 90% of all thyroid hormone)

• much T4 converted to T3 by liver, kidneys, some other tissues

2 .Thyroid Gland: T4 and T3• affect metabolic rate of every cell in the body, except

brain, spleen, testes, uterus and thyroid gland

– affect other activities within these organs and glands

• readily cross membranes (diffuse through plasma membrane to bind to mitochondrial receptors and receptors in nucleus)

2 .Thyroid Gland

T4 and T3: Actions

• increase synthesis of enzymes involved in cellular respiration --> increase basal metabolic rate

– increases glucose oxidation --> ATP synthesis

• increases ATP synthesis in cytoplasm and by mitochondria

– results in increased heat production (calorigenic effect)

• work with GH to promote normal tissue growth and development, especially important to growth/development of CNS, skeletal and reproductive systems

T4 and T3: Control

• release stimulated by TSH (thyroid-stimulating hormone from adenohypophysis)

– release of TSH stimulated by TRH from hypothalamus

• release of TRH is stimulated by cold, pregnancy, low thyroxine

• release inhibited by GHIH, high glucocorticoid levels, high sex hormone levels, high iodine

Hypothyroidism• too little thyroid hormone (thyroid gland defect, inadequate TSH, TRH,

or iodine)

– Hashimoto’s thyroid – autoimmune disorder in which thyroid is attacked and function decreases

– myxedema - low BMR, constipation, puffy eyes, edema, lethargy, mental sluggishness

– endemic goiter - enlargement of thyroid gland usually due to lack of sufficient iodine

– cretinism - genetic deficiency of thyroid gland or lack of dietary iodine during development resulting in mental retardation, disproportionate growth, short body with thick tongue and neck

• treatment - reversed by iodine supplements or hormone replacement therapy

Goiter

swelling in neck due to thyroid hypertrophy both hypo- and hyperthyroidism

Hyperthyroidism• too much thyroid hormone (thyrotoxicosis)

– Grave’s disease - autoimmune disease in which abnormal antibodies similar to TSH mimic its function and continuously stimulate release of thyroid hormones; results in high BMR, sweating, rapid heart rate, weight loss, restlessness, mood shifts, fatigues easily, limited energy; also toxic goiter

– exophthalmos - protrusion of eyeballs, fibrous tissue become edematous (swollen)

• treatments - removal of thyroid gland or irradiation– patient must be on synthetic thyroid hormone the rest of

his/her life

2 .Thyroid Gland: Calcitonin (CT)• polypeptide produced by parafollicular cells• actions: decreases blood calcium levels by:

– stimulating osteoblasts (Ca2+ uptake and incorporation into bone)

– inhibiting osteoclast activities (osteoclasts break down bone matrix releasing calcium)

• control: responds directly to blood calcium levels• very rapid effect• probably more important during childhood when it

stimulates bone growth• important because at high blood Ca2+, membranes become

less permeable to Na+

3 .Parathyroid Glands• 2 paired structures on posterior of thyroid gland

• oxyphyil cells - function unknown

• chief cells secrete parathyroid hormone (PTH; protein)

• actions: increases blood Ca2+ by:

– stimulating osteoclast activity (which break down bone matrix) while inhibiting osteoblasts (which form bone matrix)

– stimulating increased reabsorption of Ca2+ by kidney

– indirectly stimulating increased absorption of Ca2+ by small intestine by causing secretion of calcitrol form kidneys

3 .Parathyroid Glands

http://www.usc.edu/hsc/dental/ghisto/end/

c_32.html

Hyperparathyroidism

• rare; caused by parathyroid gland tumor

• results in hypercalcemia (excess Ca2+ levels in blood) --> depression of nervous system (because of effect on sodium permeability), abnormal reflexes, skeletal muscle weakness, nausea, vomiting, kidney stones, calcium deposits in soft tissues; bones become soft

Hypoparathyroidism

• trauma to or removal of parathyroid gland

• results in hypocalcemia (low blood Ca2+) --> neurons become

too excitable --> muscle tetany --> spasms/cramps -->

respiratory paralysis --> death

4 .Adrenal Glands• located in abdominal cavity against back wall

(retroperitoneal), superior to kidney• surrounded by connective tissue capsule• two regions:

– cortex - outer region, “glandular”, three zones• zona glomerulosa - outer zone• zona fasciculata - middle zone• zona reticularis - inner zone

– medulla - inner region, modified neural tissue (develops from same tissue in embryo as ganglionic [postganglionic] neurons of sympathetic division)

4 .Adrenal Gland: Regions and Zones

Adrenal Cortex: Zona Glomerulosa• produces steroid hormones based on cholesterol

• mineralocorticoids - ion (and water) balance

– main hormone is aldosterone

• action:

* stimulates reabsorption of Na+ and secretion of K+ from kidney, sweat glands, salivary glands, pancreas

– secondarily, increases water reabsorption in kidney (water follows Na+)

Adrenal Cortex: Zona Glomerulosacontrol:

• aldosterone release stimulated by:

– high K+, low Na+

– angiotensin II (result of renin-angiotensin pathway stimulated by low blood pressure),

– ACTH (when under severe stress)

• inhibited by low K+, high Na+

Adrenal Cortex: Zona Glomerulosa

Disorders:

• aldosteronism = hypersecretion (adrenal tumor)

→ increased water and Na+ reabsorption --> hypertension, edema;

→ loss of K+ --> disruption of neural and muscle function

Adrenal Cortex: Zona GlomerulosaDisorders:• Addison’s Disease = hyposecretion glucocorticoids and

mineralocorticoids– results in decreased Na+ and water reabsorption,

increased blood K+ --> low blood volume --> hypotension, dehydration;

– changes in membrane potentials --> disruption in neural and muscular function

– also decreased cortisol secretion by zona fasciculata --> decreased blood glucose levels (especially during prolonged stress)

Adrenal Cortex: Zona Fasciculata• glucocorticoids - effects on glucose metabolism

• main hormone is cortisol (hydrocortisone)

• actions:

– maintains blood glucose levels, especially in times of stress, by:

• promoting gluconeogenesis (making new glucose in liver) and use of alternative fuels by other cells (saves glucose for the brain)

– anti-inflammatory decrease immune response

* can be used clinically to treat allergic reactions (e.g., poison ivy), rheumatoid arthritis

Adrenal Cortex: Zona Fasciculata• Control

– stimulated by ACTH

– inhibited by cortisol (inhibits secretion of CRH from hypothalamus)

– blood levels peak in the morning

Disorders:

• Addison’s Disease

- hyposecretion of glucocorticoids and mineralocorticoids

Zona Fasciculata: Cushing’s Disease• hypersecretion of glucocorticoids • caused by hypersecretion of ACTH due to tumor in ZF,

pituitary, lungs, kidneys, or pancreas• suppresses glucose metabolism resulting in

– hyperglycemia (elevated glucose= steroid diabetes), – stimulates lipid metabolism (weight loss), – loss of muscle and bone mass,– “buffalo neck” and “moon face” (fat redistribution),– anti-inflammatory effects (mask infection)– water and salt retention (effect of aldosterone

hypersecretion --> water retention --> hypertension)

Adrenal Cortex: Zona Reticularis• gonadocorticoids

• most are androgens (“male” sex hormones) - converted to testosterone; small amounts of estrogens

• actions: may contribute to onset of puberty (levels rise between 7 and 13 years of age; exact function compared to hormones from ovaries or testes unclear)

• control: stimulated by ACTH

Adrenal Cortex: Zona Reticularis

• hypersecretion results in:

– masculinization and masculine pattern of hair distribution in females

– in males - rapid maturation of reproductive organs, secondary sex characteristics; hypersecretion of estrogens causes feminization and gynecomastia (enlarged breasts)

Adrenal Medulla• chromaffin cells (modified neurons - arise from

same embryonic tissue as postganglionic neurons of sympathetic division)

• catecholamines - epinephrine (~80%), norepi (NE)

• control: secretion stimulated by preganglionic fibers of sympathetic nerves during flight-or-fight response

Adrenal Medulla• actions:

– epinephrine (more potent) - increases HR (beta receptors), bronchodilation (in lungs), increased blood glucose (breakdown of glycogen in liver and skeletal muscle, and breakdown of adipose tissue)

– NE - peripheral vasoconstriction --> increased BP