© 2013 Pearson Education, Inc. Thyroid Gland Two lateral lobes connected by median mass called isthmus Composed of follicles that produce glycoprotein.

© 2013 Pearson Education, Inc.

Thyroid Gland

• Two lateral lobes connected by median mass called isthmus

• Composed of follicles that produce glycoprotein thyroglobulin

• Colloid (thyroglobulin + iodine) fills lumen of follicles and is precursor of thyroid hormone

• Parafollicular cells produce the hormone calcitonin


Figure 16.9 The thyroid gland.

Hyoid bone

Thyroid cartilage

Common carotidartery

Inferior thyroidartery

Trachea

Aorta

Gross anatomy of the thyroid gland, anterior view

Epiglottis

Superior thyroidartery

Isthmus ofthyroid gland

Left subclavianartery

Left laterallobe of thyroidgland

Colloid-filledfollicles Follicular cells

Parafollicular cells

Photomicrograph of thyroid glandfollicles (145x)


Thyroid Hormone (TH)

• Actually two related compounds– T4 (thyroxine); has 2 tyrosine molecules + 4

bound iodine atoms

– T3 (triiodothyronine); has 2 tyrosines + 3 bound iodine atoms

• Affects virtually every cell in body


Thyroid Hormone

• Major metabolic hormone

• Increases metabolic rate and heat production (calorigenic effect)

• Regulation of tissue growth and development– Development of skeletal and nervous systems– Reproductive capabilities

• Maintenance of blood pressure


Synthesis of Thyroid Hormone

• Thyroid gland stores hormone extracellularly

• Thyroglobulin synthesized and discharged into follicle lumen

• Iodides (I–) actively taken into cell and released into lumen

• Iodide oxidized to iodine (I2),

• Iodine attaches to tyrosine, mediated by peroxidase enzymes


Synthesis of Thyroid Hormone

• Iodinated tyrosines link together to form T3 and T4

• Colloid is endocytosed and combined with lysosome

• T3 and T4 are cleaved and diffuse into bloodstream


Figure 16.10 Synthesis of thyroid hormone. Slide 1

Thyroglobulin is synthesized and discharged into the follicle lumen. 1

2

3

4

5

6

7

Golgiapparatus

Iodide (I−)

RoughER

Capillary

Iodide (I–) is trapped (actively transported in).

Lysosome

Lysosomal enzymes cleave T4 and T3 from thyroglobulin and hormones diffuse into bloodstream.

Thyroglobulin colloid is endocytosed and combined with a lysosome.

Iodinated tyrosines are linked together to form T3 and T4.

Iodide is oxidized to iodine.

Iodine is attached to tyrosine in colloid, forming DIT and MIT.

To peripheral tissues

Colloid inlumen offollicle

Thyroid follicular cells

Tyrosines (part of thyroglobulinmolecule)

Thyro-globulincolloid

T3

T4

T3

T4

T3

T4

IodineDIT MIT

Colloid




Golgiapparatus

RoughER

Capillary




Colloid




Golgiapparatus

RoughER

Capillary




Colloid

2Iodide (I−) Iodide (I–) is trapped (actively transported in).




Golgiapparatus

RoughER

Capillary




Colloid


Iodine

3 Iodide is oxidized to iodine.




Golgiapparatus

RoughER

Capillary




Colloid


Iodine


4 Iodine is attached to tyrosine in colloid, forming DIT and MIT.

Thyro-globulincolloidDIT MIT




Golgiapparatus

RoughER

Capillary




Colloid


Iodine




5 Iodinated tyrosines are linked together to form T3 and T4.

T3

T4




Golgiapparatus

RoughER

Capillary




Colloid


Iodine




5 Iodinated tyrosines are linked together to form T3 and T4.

T3

T4

6

Lysosome





2

3

4

5

6

7

Golgiapparatus

Iodide (I−)

RoughER

Capillary

Iodide (I–) is trapped (actively transported in).

Lysosome

Lysosomal enzymes cleave T4 and T3 from thyroglobulin and hormones diffuse into bloodstream.


Iodinated tyrosines are linked together to form T3 and T4.

Iodide is oxidized to iodine.

Iodine is attached to tyrosine in colloid, forming DIT and MIT.

To peripheral tissues




Thyro-globulincolloid

T3

T4

T3

T4

T3

T4

IodineDIT MIT

Colloid


Transport and Regulation of TH

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

• Both bind to target receptors, but T3 is ten times more active than T4

• Peripheral tissues convert T4 to T3


Transport and Regulation of TH

• Negative feedback regulation of TH release – Rising TH levels provide negative feedback

inhibition on release of TSH– Hypothalamic thyrotropin-releasing hormone

(TRH) can overcome negative feedback during pregnancy or exposure to cold


Hypothalamus

TRH

Anterior pituitary

TSH

Thyroid gland

Thyroidhormones

Target cellsStimulates

Figure 16.8 Regulation of thyroid hormone secretion.

Inhibits


Homeostatic Imbalances of TH

• Hyposecretion in adults—myxedema; goiter if due to lack of iodine

• Hyposecretion in infants—cretinism

• Hypersecretion—Graves' disease


Figure 16.11 Thyroid disorders.


Calcitonin

• Produced by parafollicular (C) cells

• No known physiological role in humans

• Antagonist to parathyroid hormone (PTH)

• At higher than normal doses– Inhibits osteoclast activity and release of Ca2+

from bone matrix– Stimulates Ca2+ uptake and incorporation into

bone matrix


Parathyroid Glands

• Four to eight tiny glands embedded in posterior aspect of thyroid

• Contain oxyphil cells (function unknown) and parathyroid cells that secrete parathyroid hormone (PTH) or parathormone

• PTH—most important hormone in Ca2+ homeostasis


Figure 16.12 The parathyroid glands.

Parathyroidglands

Parathyroidcells(secreteparathyroidhormone)

Capillary

Oxyphilcells

Pharynx(posterioraspect)

Thyroidgland

Esophagus

Trachea


Parathyroid Hormone

• Functions– Stimulates osteoclasts to digest bone matrix

and release Ca2+ to blood – Enhances reabsorption of Ca2+ and secretion

of phosphate by kidneys– Promotes activation of vitamin D (by kidneys);

increases absorption of Ca2+ by intestinal mucosa

• Negative feedback control: rising Ca2+ in blood inhibits PTH release


Figure 16.13 Effects of parathyroid hormone on bone, the kidneys, and the intestine.

Osteoclast activityin bone causes Ca2+

and PO43- release

into blood

Hypocalcemia(low blood Ca2+)

PTH release fromparathyroid gland

Ca2+ reabsorptionin kidney tubule

Activation ofvitamin D by kidney

Ca2+ absorptionfrom food in small

intestine

Ca2+ in blood

Initial stimulus

Physiological response

Result


Homeostatic Imbalances of PTH

• Hyperparathyroidism due to tumor– Bones soften and deform– Elevated Ca2+ depresses nervous system and

contributes to formation of kidney stones

• Hypoparathyroidism following gland trauma or removal or dietary magnesium deficiency– Results in tetany, respiratory paralysis, and

death


Adrenal (Suprarenal) Glands

• Paired, pyramid-shaped organs atop kidneys

• Structurally and functionally are two glands in one– Adrenal medulla—nervous tissue; part of

sympathetic nervous system– Adrenal cortex—three layers of glandular

tissue that synthesize and secrete corticosteroids


Adrenal Cortex

• Three layers of cortex produce the different corticosteroids– Zona glomerulosa—mineralocorticoids– Zona fasciculata—glucocorticoids– Zona reticularis—gonadocorticoids


Figure 16.14 Microscopic structure of the adrenal gland.

Med

ulla

Cort

ex

Capsule

Zonaglomerulosa

Zonafasciculata

Zonareticularis

Adrenalmedulla

Adrenal gland• Medulla

• Cortex

Kidney

Hormonessecreted

Aldosterone

Cortisolandandrogens

Epinephrineandnorepinephrine

Photomicrograph (115x) Drawing of the histology of theadrenal cortex and a portion ofthe adrenal medulla


Mineralocorticoids

• Regulate electrolytes (primarily Na+ and K+) in ECF– Importance of Na+: affects ECF volume, blood

volume, blood pressure, levels of other ions– Importance of K+: sets RMP of cells

• Aldosterone most potent mineralocorticoid – Stimulates Na+ reabsorption and water

retention by kidneys; elimination of K+


Aldosterone

• Release triggered by– Decreasing blood volume and blood pressure– Rising blood levels of K+


Mechanisms of Aldosterone Secretion

• Renin-angiotensin-aldosterone mechanism: decreased blood pressure stimulates kidneys to release renin triggers formation of angiotensin II, a potent stimulator of aldosterone release

• Plasma concentration of K+: increased K+ directly influences zona glomerulosa cells to release aldosterone

• ACTH: causes small increases of aldosterone during stress

• Atrial natriuretic peptide (ANP): blocks renin and aldosterone secretion to decrease blood pressure


Figure 16.15 Major mechanisms controlling aldosterone release from the adrenal cortex.

Blood volumeand/or blood

pressure

K+ in blood Stress Blood pressureand/or blood

volume

Hypo-thalamus

Heart

CRH

Anteriorpituitary

Directstimulatingeffect

Initiatescascadethatproduces

Renin

Angiotensin II

ACTH Atrial natriureticpeptide (ANP)

Inhibitoryeffect

Zona glomerulosaof adrenal cortex

Enhancedsecretionof aldosterone

Targetskidney tubules

Absorption of Na+ andwater; increased K+ excretion

Blood volumeand/or blood pressure

Kidney

Primary regulators Other factors


Homeostatic Imbalances of Aldosterone

• Aldosteronism—hypersecretion due to adrenal tumors– Hypertension and edema due to excessive Na+

– Excretion of K+ leading to abnormal function of neurons and muscle


Glucocorticoids

• Keep blood glucose levels relatively constant

• Maintain blood pressure by increasing action of vasoconstrictors

• Cortisol (hydrocortisone)– Only one in significant amounts in humans

• Cortisone

• Corticosterone


Glucocorticoids: Cortisol

• Released in response to ACTH, patterns of eating and activity, and stress

• Prime metabolic effect is gluconeogenesis—formation of glucose from fats and proteins– Promotes rises in blood glucose, fatty acids, and

amino acids

• "Saves" glucose for brain• Enhances vasoconstriction rise in blood

pressure to quickly distribute nutrients to cells


Homeostatic Imbalances of Glucocorticoids

• Hypersecretion—Cushing's syndrome/disease– Depresses cartilage and bone formation– Inhibits inflammation– Depresses immune system– Disrupts cardiovascular, neural, and

gastrointestinal function

• Hyposecretion—Addison's disease– Also involves deficits in mineralocorticoids

• Decrease in glucose and Na+ levels• Weight loss, severe dehydration, and hypotension


Figure 16.16 The effects of excess glucocorticoid.

Patient before onset. Same patient with Cushing’s syndrome. The white arrow shows the characteristic “buffalo hump” of fat on the upper back.


Gonadocorticoids (Sex Hormones)

• Most weak androgens (male sex hormones) converted to testosterone in tissue cells, some to estrogens

• May contribute to– Onset of puberty– Appearance of secondary sex characteristics– Sex drive in women – Estrogens in postmenopausal women


Gonadocorticoids

• Hypersecretion– Adrenogenital syndrome (masculinization)– Not noticeable in adult males– Females and prepubertal males

• Boys – reproductive organs mature; secondary sex characteristics emerge early

• Females – beard, masculine pattern of body hair; clitoris resembles small penis


Adrenal Medulla

• Medullary chromaffin cells synthesize epinephrine (80%) and norepinephrine (20%)

• Effects– Vasoconstriction– Increased heart rate– Increased blood glucose levels– Blood diverted to brain, heart, and skeletal

muscle


Adrenal Medulla

• Responses brief

• Epinephrine stimulates metabolic activities, bronchial dilation, and blood flow to skeletal muscles and heart

• Norepinephrine influences peripheral vasoconstriction and blood pressure


Adrenal Medulla

• Hypersecretion– Hyperglycemia, increased metabolic rate,

rapid heartbeat and palpitations, hypertension, intense nervousness, sweating

• Hyposecretion– Not problematic– Adrenal catecholamines not essential to life


Figure 16.17 Stress and the adrenal gland.

Short-term stress Prolonged stress

Nerve impulses

Spinal cord

Preganglionicsympatheticfibers

Adrenal medulla(secretes amino acid–based hormones)

Catecholamines(epinephrine andnorepinephrine)

Short-term stress response

Stress

Hypothalamus

Corticotropic cells of anterior pituitary

To target in blood

CRH (corticotropin-releasing hormone)

Adrenal cortex(secretes steroidhormones)

Mineralocorticoids Glucocorticoids

ACTH

• Heart rate increasesLong-term stress response

• Kidneys retain sodium and water

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

• Blood pressure increases• Bronchioles dilate• Liver converts glycogen to glucose and releases glucose to blood• Blood flow changes, reducing digestive system activity and urine output• Metabolic rate increases

• Blood volume and blood pressure rise • Immune system

supressed


Pineal Gland

• Small gland hanging from roof of third ventricle • Pinealocytes secrete melatonin, derived from

serotonin• Melatonin may affect

– Timing of sexual maturation and puberty– Day/night cycles– Physiological processes that show rhythmic variations

(body temperature, sleep, appetite)– Production of antioxidant and detoxification molecules

in cells


Pancreas

• Triangular gland partially behind 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 () cells produce glucagon (hyperglycemic

hormone)• Beta () cells produce insulin (hypoglycemic

hormone)


Figure 16.18 Photomicrograph of differentially stained pancreatic tissue.

Pancreatic islet

• (Glucagon- producing) cells

• (Insulin- producing) cells

Pancreatic acinarcells (exocrine)


Glucagon

• Major target—liver

• Causes increased blood glucose levels

• Effects– Glycogenolysis—breakdown of glycogen to

glucose– Gluconeogenesis—synthesis of glucose

from lactic acid and noncarbohydrates– Release of glucose to blood


Insulin

• Effects of insulin– Lowers blood glucose levels– Enhances membrane transport of glucose into

fat and muscle cells– Inhibits glycogenolysis and gluconeogenesis– Participates in neuronal development and

learning and memory

• Not needed for glucose uptake in liver, kidney or brain


Insulin Action on Cells

• Activates tyrosine kinase enzyme receptor

• Cascade increased glucose uptake

• Triggers enzymes to– Catalyze oxidation of glucose for ATP

production – first priority– Polymerize glucose to form glycogen– Convert glucose to fat (particularly in adipose

tissue)


Figure 16.19 Insulin and glucagon from the pancreas regulate blood glucose levels.Stimulates glucoseuptake by cells

Insulin

Stimulatesglycogenformationw

Pancreas

Tissue cells

Glucose Glycogen

LiverBloodglucosefalls tonormalrange.

IMBALANCEStimulus Bloodglucose level BALANCE: Normal blood glucose level (about 90 mg/100 ml)

Pancreas

IMBALANCE

Glucose Glycogen

Liver Stimulatesglycogenbreakdown

Bloodglucoserises tonormalrange.

Stimulus Bloodglucose level

Glucagon


Factors That Influence Insulin Release

• Elevated blood glucose levels – primary stimulus• Rising blood levels of amino acids and fatty

acids• Release of acetylcholine by parasympathetic

nerve fibers• Hormones glucagon, epinephrine, growth

hormone, thyroxine, glucocorticoids• Somatostatin; sympathetic nervous system


Homeostatic Imbalances of Insulin

• Diabetes mellitus (DM)– Due to hyposecretion (type 1) or hypoactivity (type 2)

of insulin– Blood glucose levels remain high nausea higher

blood glucose levels (fight or flight response)– Glycosuria – glucose spilled into urine– Fats used for cellular fuel lipidemia; if severe

ketones (ketone bodies) from fatty acid metabolism ketonuria and ketoacidosis

– Untreated ketoacidosis hyperpnea; disrupted heart activity and O2 transport; depression of nervous system coma and death possible


Diabetes Mellitus: Signs

• Three cardinal signs of DM– Polyuria—huge urine output

• Glucose acts as osmotic diuretic

– Polydipsia—excessive thirst• From water loss due to polyuria

– Polyphagia—excessive hunger and food consumption

• Cells cannot take up glucose; are "starving"


Homeostatic Imbalances of Insulin

• Hyperinsulinism:– Excessive insulin secretion

– Causes hypoglycemia• Low blood glucose levels• Anxiety, nervousness, disorientation,

unconsciousness, even death

– Treated by sugar ingestion


Table 16.4 Symptoms of Insulin Deficit (Diabetes Mellitus)


Ovaries and Placenta

• Gonads produce steroid sex hormones– Same as those of adrenal cortex

• Ovaries produce estrogens and progesterone– Estrogen

• Maturation of reproductive organs• Appearance of secondary sexual characteristics • With progesterone, causes breast development and cyclic

changes in uterine mucosa

• Placenta secretes estrogens, progesterone, and human chorionic gonadotropin (hCG)


Testes

• Testes produce testosterone – Initiates maturation of male reproductive

organs– Causes appearance of male secondary

sexual characteristics and sex drive– Necessary for normal sperm production– Maintains reproductive organs in functional

state


Other Hormone-producing Structures

• Adipose tissue– Leptin – appetite control; stimulates

increased energy expenditure– Resistin – insulin antagonist– Adiponectin – enhances sensitivity to insulin



• Enteroendocrine cells of gastrointestinal tract– Gastrin stimulates release of HCl– Secretin stimulates liver and pancreas– Cholecystokinin stimulates pancreas,

gallbladder, and hepatopancreatic sphincter– Serotonin acts as paracrine



• Heart– Atrial natriuretic peptide (ANP) decreases

blood Na+ concentration, therefore blood pressure and blood volume

• Kidneys– Erythropoietin signals production of red

blood cells– Renin initiates the renin-angiotensin-

aldosterone mechanism



• Skeleton (osteoblasts)– Osteocalcin

• Prods pancreas to secrete more insulin; restricts fat storage; improves glucose handling; reduces body fat

• Activated by insulin• Low levels of osteocalcin in type 2 diabetes –

perhaps increasing levels may be new treatment

• Skin– Cholecalciferol, precursor of vitamin D


• Thymus– Large in infants and children; shrinks as age– Thymulin, thymopoietins, and thymosins

• May be involved in normal development of T lymphocytes in immune response

• Classified as hormones; act as paracrines



Developmental Aspects

• Hormone-producing glands arise from all three germ layers

• Most endocrine organs operate well until old age• Exposure to pesticides, industrial chemicals,

arsenic, dioxin, and soil and water pollutants disrupts hormone function

• Sex hormones, thyroid hormone, and glucocorticoids are vulnerable to the effects of pollutants

• Interference with glucocorticoids may help explain high cancer rates in certain areas



• Ovaries undergo significant changes with age and become unresponsive to gonadotropins; problems associated with estrogen deficiency occur

• Testosterone also diminishes with age, but effect is not usually seen until very old age



• GH levels decline with age - accounts for muscle atrophy with age

• TH declines with age, contributing to lower basal metabolic rates

• PTH levels remain fairly constant with age, but lack of estrogen in older women makes them more vulnerable to bone-demineralizing effects of PTH

© 2013 Pearson Education, Inc. Thyroid Gland Two lateral lobes connected by median mass called isthmus Composed of follicles that produce glycoprotein.

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