THE ENDOCRINE SYSTEMTHE ENDOCRINE SYSTEM

Ch 17, Human AnatomyCh 17, Human Anatomy

Sonya Schuh-Huerta, Ph.D.Sonya Schuh-Huerta, Ph.D.

The Endocrine System: An Overview

• A system of ductless glands– Secrete messenger molecules called

hormones

• Interacts closely with the nervous system

• Endocrinology– Study of hormones & endocrine glands

Endocrine Organs

• Scattered throughout the body• Pure endocrine organs

– Pituitary, pineal, thyroid, parathyroid, & adrenal glands

• Organs containing endocrine cells– Pancreas, thymus, gonads, & hypothalamus

• Hypothalamus is a neuroendocrine organ– Produces hormones & also has nervous functions

Location of the Major Endocrine Glands

Pineal gland

HypothalamusPituitary gland

Parathyroid glands(on dorsal aspect of thyroid gland)

Thymus

Thyroid gland

Adrenal glands

Pancreas

Ovary (female)

Testis (male)

Hormones

• Classes of hormones– Amino acid–based hormones– Steroids derived from cholesterol

• Basic hormone action– Circulate throughout the body in the blood– Influences only specific tissues target

cells• A hormone can have different effects on different

target cells

Control of Hormone Secretion

• Secretion triggered by 3 major types of stimuli– Humoral simplest of endocrine control

mechanisms• Secretion in direct response to changing ion or

nutrient levels in the blood• Parathyroid monitors calcium levels

– Responds to decline by secreting hormone to reverse decline

Control of Hormone Secretion

• Secretion triggered by 3 major types of stimuli (cont…)– Neural

• Nerve fibers stimulate hormone secretion• Sympathetic nerve fibers stimulate cells in the

adrenal medulla• Induces release of epinephrine & norepinephrine

– Hormonal• Certain hormones trigger secretion of other

hormones– Hypothalamus secretes hormones stimulates pituitary

to secrete hormones stimulates other glands to secrete hormones

3 Major Types of Stimuli(a) Humoral stimulus (b) Neural stimulus (c) Hormonal stimulus

Capillary (low Ca2+

in blood)

Parathyroidglands

Thyroid gland(posterior view)

PTH

Parathyroidglands

CNS (spinal cord)

Medulla ofadrenal gland

Preganglionicsympatheticfibers

Capillary

Hypothalamus

Thyroidgland

Adrenalcortex

Gonad(Testis)

Pituitarygland

Capillary blood contains low concentration of Ca2+, which stimulates…

Preganglionic sympathetic fibersstimulate adrenal medulla cells…

The hypothalamus secretes hormones that…

…stimulatethe anteriorpituitary glandto secretehormonesthat…

…secretion of parathyroid hormone (PTH) by parathyroid glands. PTH acts to increase blood Ca2+.

…to secrete catecholamines(epinephrine and norepinephrine)

…stimulate other endocrine glandsto secrete hormones

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Control of Hormone Secretion

• Always controlled by feedback loops– Blood concentration declines below a

minimum• More hormone is secreted

– Blood concentration exceeds maximum• Hormone production is halted

• Referred to as positive & negative feedback loops usually multiple hormones involved in the pathway

The Pituitary Gland

• Secretes 9 major hormones

• Attached to the hypothalamus by the infundibulum (= pituitary stalk)

• 2 basic divisions of the pituitary gland:– Adenohypophysis (= anterior pituitary)

• Has 3 major divisions

– Neurohypophysis (= posterior pituitary) has 2 major divisions

The Pituitary Gland

Tuber cinereum

Mammillarybody

InfundibulumPars nervosa

Pars tuberalis Pars intermedia Pars distalis

Median eminence of hypothalamus

Optic chiasma

(c)

Anterior lobePosterior lobe

(a)

(d)

Acidophil Basophil Chromophobe cell

Capillary withred blood cells

Spherical cluster of cells

(b)

Corpuscallosum

Pituitary (hypophysis)

Brain stem

Mammillarybody

Hypothalamus

Pineal

Thalamus

Anterior Pituitary

• The largest division of the anterior lobe:– Makes & secretes 7 different hormones– Tropic hormones regulate the hormone

secretion of other glands• Includes: TSH, ACTH, FSH, LH

Anterior Pituitary

• GH, PRL, & MSH– Act directly on non-endocrine target tissues

Anterior Pituitary

• Growth hormone/GH (= somatotropic hormone)– Produced by somatotropic cells– Stimulates body growth by stimulating

increased protein production & growth of epiphyseal plates

– Stimulates growth directly & indirectly by the liver’s secretion of insulin-like growth factor-1 (IGF1)

Anterior Pituitary

• Thyroid-stimulating hormone (TSH)– Produced by thyrotropic cells– Signals thyroid gland to secrete thyroid

hormones

• Adrenocorticotropic hormone (ACTH)– Stimulates adrenal cortex to secrete

hormones that help cope with stress

Anterior Pituitary

• Melanocyte-stimulating hormone (MSH)– In humans, MSH functions in appetite

supression (“My Stomach’s not Hungry” hormone)

• Gonadotropins FSH & LH – Produced by gonadotropic cells

– they increase sex steroid production by the

gonads & the maturation of gametes

Anterior Pituitary

• Prolactin (PRL) produced by prolactin cells– Targets milk-producing glands in the breast

stimulates milk production after childbirth &

during lactation

– There are prolactin-secreting tumors that result in milk production in both women & men

(galactorrhea; can lead to problems with fertility)

– Prolactin central to milk production in all female mammals (exception – male bats)

Anterior Pituitary

Anterior Pituitary

• The hypothalamus– Controls secretion of anterior lobe hormones– Exerts control by secreting:

• Releasing hormones prompt anterior lobe to release hormones

• Gonadotropin-releasing hormone (GnRH) produced & secreted by specific neurons of hypothalamus cause release of FSH & LH

• Inhibiting hormones turn off secretion of anterior lobe hormones

Hypothalamic Control of Hormone Secretion from the Anterior Lobe

• Releasing hormones– Are secreted like neurotransmitters– Enter a primary capillary plexus– Travel in hypophyseal portal veins to a

secondary capillary plexus• From the secondary capillary plexus, the releasing

hormones trigger the anterior lobe to secrete the specific hormone, which is dumped into the secondary capillary plexus, and enters general circulation & travels to target organs

Hypothalamic Control of Hormone Secretion from the Anterior Lobe

Hypothalamic Control of Ant. Pituitary Secretion

When appropriately stimulated, hypothalamic neurons secrete releasing and inhibiting hormones into the primary capillary plexus.

Hypothalamic hormones travel through the portal veins to the anterior pituitary where they stimulate or inhibit release of hormones from the anterior lobe.

Anterior pituitary hormones are secreted into the secondary capillary plexus.

HypothalamusHypothalamic neuroncell bodies

Hypophysealportal system

Superior hypophysealartery

(a) Relationship between the anterior pituitary & hypothalamus

Anterior lobeof pituitary

TSH, FSH, LH, ACTH, GH, PRL

Primary capillaryplexus

Hypophysealportal veins

Secondarycapillaryplexus

1

2

3

Posterior Pituitary

• Is structurally part of the brain

• Its axons make up the hypothalamic–hypophyseal tract– Arises from neuronal cell bodies in the

hypothalamus• Supraoptic nucleus• Paraventricular nucleus

Relationship Between Posterior Pituitary & Hypothalamus

Hypothalamic neuronssynthesize oxytocin and ADH.

Oxytocin and ADH are transported along the hypothalamic-hypophyseal tract to the posterior lobe.

Oxytocin and ADH are stored in axon terminals in the posterior pituitary.

Oxytocin and ADH are released into the blood when hypothalamic neurons fire.

Paraventricular nucleus

Supraoptic nucleus

Optic chiasma

Hypothalamus

Inferiorhypophysealartery

OxytocinADH

Infundibulum (connecting stalk)Hypothalamic-hypophysealtract

Axon terminals

Posteriorlobe ofpituitary

(b) Relationship between the posterior pituitary & hypothalamus

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2

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4

Posterior Pituitary

• Does not make hormones

• Stores & releases hormones made in the hypothalamus!

• Releases 2 very important peptide hormones:– Anti-Diuretic hormone (ADH) –remember this?– Oxytocin

Posterior Pituitary

• ADH (Anti-Diuretic hormone; =vasopressin)– Targets kidneys to resorb water; prevents

diuresis

• Oxytocin– Induces smooth muscle contraction of

reproductive organs, ejects milk during breast feeding, & signals contraction of the uterus during childbirth

Hormones Made by Hypothalamus & Secreted by Posterior Pituitary

Pineal Gland

• Located on the roof of the diencephalon

• Shaped like a pine cone

• Pinealocytes secrete melatonin – A hormone that regulates circadian rhythms

Thyroid Gland

• Located in anterior neck around trachea• Largest pure endocrine gland• Functions in metabolism & metabolic rate; how

quickly the body uses energy; making proteins, etc.• Composed of follicles & areolar

connective tissue

Thyroid GlandHyoid bone

Thyroid cartilage

Common carotidartery

Epiglottis

Superior thyroidartery

External carotidartery

Isthmus ofthyroid gland

Left subclavianartery

Left laterallobe of thyroidgland

Inferior thyroidartery

Trachea

Rightsubclavianartery

Aorta

(a) Gross anatomy of the thyroid gland, anterior view

Thyroid Gland Hormones• Produces 2 types of hormones:

– Thyroid hormones (TH = T3 & T4) – Thyroxine (T4) & triiodothyronine (T3) tyrosine-based

hormones produced by thyroid – Involved in regulation of metabolism act on nearly all

cells of body; increase basal metabolic rate, protein synthesis; long bone growth; increase body’s sensitivity to catecholamines; regulate protein, fat & carb metabolism

– Secreted by follicular cells– Calcitonin Secreted by parafollicular cells; lowers

blood Ca2+ levels (inhibits intestinal Ca2+ absorption & inhibits osteoclast activity in bones; protects against calcium loss from skeleton during pregnancy & lactation

Microscopic Anatomy of Thyroid GlandColloid-filledfollicles

Follicular cells(secrete thyroid hormone)

Parafollicular cell(secretes calcitonin)

(b) Photomicrograph of thyroid gland follicles (160)

Parathyroid Glands

• Lie on the posterior surface of thyroid gland

• Contain 2 types of endocrine cells– Chief cells

• Produce Parathyroid Hormone (PTH)• Functions to increase blood Ca2+

levels by acting on receptors in bone, kidney & intestine all leads to higher plasma calcium levels! (opposite of calcitonin)

– Oxyphil cells• Function unknown...

Parathyroid Glands: Gross & Microscopic

(b) Photomicrograph of parathyroid glandtissue (360)

Capillary

Parathyroidcells(secreteparathyroidhormone)

Oxyphilcells

Pharynx(posterioraspect)

Thyroidgland Parathyroid

glands

Trachea

Esophagus

(a) Location of parathyroid glands, posterior view

• Pyramid-shaped glands located on the superior surface of each kidney

• Supplied by about 60 suprarenal arteries

• Nerve supply is almost exclusively sympathetic fibers!!!

• Functions in…? -remember?

Adrenal Glands (Suprarenal Glands)

Adrenal Glands

• 2 endocrine glands in one!– Adrenal medulla a cluster

of neurons• Part of Sympathetic Nervous System!• Postganglionic nerve fibers

– Adrenal cortex forms the bulk of the gland

• Functions All adrenal hormones help one cope with danger, terror, or stress

Adrenal Medulla

• Chromaffin cells– Are modified ganglionic sympathetic neurons– Secrete amine hormones epinephrine &

norepinephrine (= catecholamines) • Enhance “fight-or-flight” response• Hormones are stored in secretory vesicles

– Are arranged in spherical clusters & some branching cords

Adrenal Cortex

• Secretes lipid-based steroid hormones glucocorticoids, mineralocorticoids, androgens, E2

• Cortex is composed of 3 layers (zones):– Zona glomerulosa cells arranged in

spherical clusters– Zona fasciculata cells arranged in parallel

cords; contains lipid droplets – Zona reticularis cells arranged in a

branching network

The Adrenal Gland: Gross & Microscopic

Cortex

Kidney

Medulla

Adrenal gland

Capsule

Aldosterone

Epinephrineandnorepinephrine

Cortisolandandrogens

Zonaglomerulosa

Zonafasciculata

Zonareticularis

Adrenalmedulla

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

(b) Photomicrograph (140X)

Hormonessecreted

Cort

ex

Med

ulla

Stress & the Adrenal GlandShort-term stress More prolonged stress

Stress

Hypothalamus

CRH (corticotropin-releasing hormone)

Corticotroph cellsof anterior pituitary

To target in blood

Adrenal cortex(secretes steroidhormones)

GlucocorticoidsMineralocorticoids

ACTH

Catecholamines(epinephrine andnorepinephrine)

Short-term stress response

1.Increased heart rate2.Increased blood pressure3.Liver converts glycogen to glucose and releasesglucose to blood4.Dilation of bronchioles5.Changes in blood flow patterns leading to decreased digestive system activity and reduced urine output6.Increased metabolic rate

Long-term stress response

1.Retention of sodiumand water by kidneys2.Increased blood volumeand blood pressure

1.Proteins and fats convertedto glucose or broken downfor energy2.Increased blood glucose3.Suppression of immunesystem

Adrenal medulla(secretes amino acid–based hormones)

Preganglionicsympatheticfibers

Spinal cord

Nerve impulses

Pancreas

• Located in the posterior abdominal wall

• Functions regulation of blood sugar, metabolism & digestion

• Contains endocrine & exocrine cells– Exocrine cells

• Acinar cells secrete digestive enzymes (remember?..)

– Endocrine cells• Islets of Langerhans• About one million islets scattered throughout the

pancreas

Islets of Langerhans

• Main endocrine cell types:– Alpha cells ( cells) secrete glucagon

• Signal liver to release glucose from glycogen• Raises blood sugar

– Beta cells ( cells) secrete insulin• Signal most body cells to take up glucose from the

blood• Promotes storage of glucose as glycogen in liver• Lowers blood sugar

Pancreas

• Pancreatic islets contain 2 rare cell types– Delta (∂) cells

• Secrete somatostatin– Inhibits secretion of insulin & glucagon

– F (PP) cells• Secrete pancreatic polypeptide (PP)

– May inhibit exocrine activity of the pancreas

Thymus

• Located in the lower neck & anterior thorax

• Function Important immune organ; T-lymphocytes arise from precursor cells here; decreases in size & function after puberty

Gonads• Main sources of sex steroid

hormones – Testes & ovaries

• Male– Interstitial Leydig cells secrete androgens

• Primarily testosterone – Promotes development of the testes– Promotes the formation & survival of sperm– Development & maintenance

of secondary sex characteristics

Gonads

• Female– Ovaries

• Androgens & estrogens secreted by follicular cells

• Estrogen– Dev & maintenance of secondary sex

characteristics

– Dev of eggs– Regulation of menstrual cycle

• Progesterone– Prepares the uterus for Pregnancy

Sex Steroid Hormones

• Critical for normal reproductive function

• Affect many other tissues/organs of the body• Bone• Muscle• Fat• Liver & kidney• Brain (sexual behavior, mood, cognition)

Sex Steroid Hormones & Bone

• Promote bone growth (adolescent growth spurt)

2008 2010

Sex Steroid Hormones & Bone

• Also maintain bone mass• With aging or in diseases that render the gonads

dysfunctional (low T/E2) loss of bone mass & osteoporosis!

Could Skeletal Tissue Exert Reciprocal Effects on Gonads?

gonad

sex steroids

???

bone

Osteocalcin – A Hormone Secreted by Bone

• Secreted by osteoblasts (bone-forming cells of skeleton)• Involved in bone growth & bone remodeling• Roles in energy metabolism & glucose homeostasis -Ocn-/- mice have skeletal & metabolic defects greater bone

density, fat, & insulin resistance

(Lee et al. Cell, 2007; Ducy et al. Nature, 1996)

• Ocn-/- mice – reduced T & reduced fertility (Oury et al. Cell, 2011)

• Osteocalcin – a hormone linking bone with metabolism & reproduction

Bone & Fertility in Balance

Male Fertility(Female Fertility?)

Germ cell development(sperm)

Osteocalcin (Ocn)

Functional gonad (testis)

Healthy bones(bone mass)

Ocn binding to receptor

G s

Ado

GTP

Testosterone

(& other factors)

Energy Metabolism

Testosterone/Estrogen

AgingFertility DisordersMetabolic DysfunctionGenesEnvironmental factors

AgingFertility DisordersMetabolic DysfunctionGenesEnvironmental factors

Other Endocrine Structures…

• Endocrine cells occur within:– The heart

• Atria contain atrial natriuretic peptide (ANP) vasodialator; involved in control of BP

– The GI tract• Enteroendocrine cells (Ghrelin, CCK, gastrin,

secretin, motilin, enterocrinin, etc.…)• Ghrelin the hunger (“belly-growling”) hormone!

– The placenta• Sustains the fetus & secretes several hormones

(human chorionic gonadotropin, progesterone, E2, relaxin…)

Other Endocrine Structures

– The kidneys• Cells of the juxtaglomerular apparatus (JGA)

secrete renin • Endothelial cells & interstitial connective tissue

secrete erythropoietin

– The skin• With sunlight, modified cholesterol molecules

convert to a precursor of vitamin D

– Bone• Osteocalcin, & others…

Pituitary Disorders

• Gigantism – Hypersecretion of GH in children

• Pituitary dwarfism– Hyposecretion of GH

• Diabetes insipidus excessive thirst & urination– Hypothalamus does not make enough ADH

Disorders of the Pancreas: Diabetes Mellitus

• Caused by– Insufficient secretion of insulin – Resistance of body cells to the effects of

insulin

• Type 1 Diabetes– Develops suddenly, usually before age 15– T cell–mediated autoimmune response

destroys beta cells of pancreas no more insulin

Diabetes Mellitus• Type 2 Diabetes

– Adult onset– Usually occurs after age 40– Associated with higher BMI/obesity– Body cells have decreased

sensitivity to insulin– Controlled by dietary

changes & regular exercise!

Disorders of the Thyroid

• Grave’s disease– Most common type of hyperthyroidism – Immune system makes abnormal antibodies

• Stimulates the over-secretion of TH by follicle cells

– Leads to nervousness, weight loss, sweating, & rapid heart rate; protrusion of the eyeballs

– Too much thyroid action metabolism too high!

Disorders of the Thyroid

• Myxedema– Adult hypothyroidism– Antibodies attack & destroy thyroid tissue– Low metabolic rate & weight gain are common

symptoms

Disorders of the Thyroid

• Endemic goiter– Due to lack of iodine in the diet

• Cretinism– Hypothyroidism in children– Short, disproportionate body, thick tongue,

& mental retardation

Thyroid Disorders

Disorders of the Adrenal Cortex

• Cushing’s syndrome– Caused by hypersecretion of glucocorticoid hormones

(cortisol) usually a pituitary tumor– Weight gain on trunk, fat pads, “moon face,” thinning

of the skin, striae, etc.

• Addison’s disease– Hyposecretory disorder of the adrenal cortex– Deficiencies of both mineralocorticoids &

glucocorticoids– Fatigue, weakness, weight loss, mood changes,

hyperpigmentation

Adrenal Cortex Disorders

Adrenal Cortex Disorders

Cushing’s Addison’s

The Endocrine System with Age• Endocrine organs operate effectively until old age

• Anterior pituitary – Increase in connective tissue & lipofuscin – Decrease in vascularization & number of hormone-

secreting cells• Adrenal cortex

– Normal rates of glucocorticoid secretion continue• Adrenal medulla

– No age-related changes in catecholamine secretion

•Gonads– Testes: decline in sperm counts, but can function

throughout life – Ovaries: loss of all eggs/diminished function in mid-life

Congratulations!!!! You made it to the end of Anatomy!

What’s Next?Today’s Lab: Final Lab Exam 5!Mon, May 20, 5:25 pm: Final Exam!