The Endocrine System

Endocrine System

Function:RegulatesCoordinatesIntegratesWorks cooperatively with the nervous systemNo ducts: Reactions not immediate -last longer than

N.S. responses

Hormones

Substances secreted by cells that regulate the activity of another tissue or organ

Most produced by glandsSome produced by clusters of cellsSome produced by neurons (neurohormones)

Hormones

Types of HormonesAmino Acid DerivativesSimple amines, thyroxin, peptides and proteins Examples:

Thyroid hormones, epinephrine and NE, insulin, glucagon

Most hormones this type

Hormones

Types of hormonesSteroid hormonesDerived from cholesterol Includes gonadal hormones (sex hormones) and

adrenal hormones (cortex only)Examples:

Progesterone, testosterone, cortisol, aldosterone

Hormones

Types of hormonesEicosanoidsAre paracrine hormones (local hormone = produced by

cells and released to effect cells in the same area)Examples:

Prostaglandins, leukotrines

Intracellular Receptors

Receptors

On the target cell -bind hormone Determine the effect the hormone will have on the

target cellBinding may cause:

Change in membrane permeability or potentialSynthesis of substances such as proteins or enzymesActivation or deactivation of enzymesSecretion of substancesStimulation of mitosis

Hormone Actions

Alter the activity of target cellsDecrease or increase cellular activity in target cellsOnly affect cells with receptors for that hormone

Hormone action: What happens when a hormone binds with a receptor?

1. Channels

2. 2nd messenger

3. Genes

HORMONE ACTION

Where are the receptors?1. On the cell membrane (AA hormones)

intracellular second messenger2. In the nucleus (steroid hormones & thyroxine)

direct gene activation

HORMONE ACTION- Second Messenger

Intracellular second messengerHormoneReceptorG proteinAdenylate cyclase systemCyclic AMPProtein kinases

Hormone Mechanisms

Second MessengersHormone binds to a

receptor on plasma membrane

Series of reactions initiated within the cell

Example: Cyclic AMP

Second MessengersCyclic AMP (cAMP)

Formed from ATP when a hormone binds to receptor

Hormone/receptor binding ‘G’ protein activates or inhibits

adenyl cyclase ATP converted to cAMP May activate protein kinases Initiates cascade of enzymes

within the cell Effect depends upon target cell

Second Messenger System

Second MessengersPIP Mechanism

PIP2 split into diacylglycerol and IP3

Both act as second messengers

IP3 triggers the release of calcium from the ER

Ca2+ acts as a third messenger

Diacylglycerol may activate protein kinases

Second messenger system

Direct Activation of GenesSteroid hormones can pass through the plasma membraneBind to receptors inside cellHormone/receptor binding stimulates genes on the DNA to begin

protein production

Gene Activation

Hormone Regulation

Nervous SystemUltimate control of hormone mechanisms belongs to the nervous systemMainly hypothalamus and sympathetic nervous system

Endocrine Gland Stimuli

Hormone Regulation

Stimulation or inhibition of endocrine glands comes from THREE sources:

Other hormones

Humoral stimuli

Neural stimuli

Hormone RegulationHormonal Regulation (by

other Hormones)Hormones may stimulate or

inhibit the release of other hormonesHypothalamus-

Regulates anterior pituitary gland

Pituitary hormones- Stimulate release of

hormones from other glands

Hormone Regulation

Regulation by Humoral Stimuli Changing ion or nutrient levels in

the blood may inhibit or stimulate the release of hormones

Example: Low blood calcium (Ca2+) PTH released from the parathyroid

glands Ca2+ released from bone Increase in blood Ca2+

Hormone Regulation

Regulation by Neural StimuliNerve impulses may stimulate

the release of hormonesExample:Sympathetic neurons

stimulate release of epinephrine and norepinephrine from the adrenal medulla

Feedback Mechanisms

Negative Feedback System Rising hormone or ion levels

inhibit further hormone release from the gland

Positive Feedback System Rising hormone levels cause

an increase in the hormone being secreted

Hypo or HypersecretionMay result in a disorderExamples:

Diabetes

Grave’s disease

Addison’s disease

Cushing’s disease

Major Endocrine GlandsPituitary Gland (Hypophysis)

Posterior lobe (Neurohypophysis)Releases 2 hormones

produced in the hypothalamus

anterior lobe

posterior lobe

Posterior Pituitary Gland

Posterior LobeDerived from hypothalamusPosterior lobe +

infundibulum = neurohypophysis

Neuron axons to pituitary = hypothalamic hypophyseal tract

hypothalamic hypophyseal tract

Posterior Pituitary Gland

Two hormones released hereBoth produced in nuclei of the

hypothalamusBoth secreted into capillaries in

posterior pituitary for distribution to the body

Oxytocin & ADH

Hypothalamus

SON/PVN – produce ADH & oxytocin

Released from posterior pituitary

Pituitary

Posterior lobe:• Pituicytes

ADH

Oxytocin

Posterior Pituitary Gland Supraoptic Nucleus

ADH (Vasopressin) Stimulates increased

reabsorption of water by kidney tubules

Decreases urine volume Increases blood volume React to Osmoreceptors

ADH & oxytocin

Paraventricular Nucleus Oxytocin Uterine contractions Milk release (Contraction

of mammary gland smooth muscle

Supraoptic nuclei

Paraventricular nuclei

Ventral Hypothalamus

Releasing and inhibiting hormonesThru portal systemTarget = anterior pituitary

Anterior Pituitary Gland

Hypophyseal Portal System

primary capillary plexus

neurons in ventral hypothalamus

hypophyseal portal veins

secondary capillary plexus

secretory cells

Anterior Pituitary Gland

Anterior Lobe = AdenohypophysisDerived from roof of mouthProduces hormonesRelease of hormones is controlled

by hormones from neurons of the ventral hypothalamus = releasing or inhibiting hormones

anterior lobe

Ventral hypothalamu

s

Pituitary (Hypophysis) Location and relationships Densely packed cells (anterior)

Anterior lobe: TSH

ACTH

FSH

LH GnRH

Growth h.

Prolactin

MSH

Anterior Pituitary Gland

The following four anterior pituitary hormones are tropic hormones

Tropic Hormones:

TSH

ACTH

FSH

LH

Tropic Hormones

Hormones SecretedThyroid Stimulating Hormone (TSH)Stimulates production and release of thyroid hormones by

the thyroid gland

Release stimulated by TRH Inhibited by rising blood levels of thyroid hormone

Tropic Hormones

Hormones SecretedAdrenocorticotropic Hormone (ACTH or Corticotropin)Stimulates secretion of corticosteroid hormones (esp.

cortisol) from the adrenal cortexRelease stimulated by CRH, fever, hypoglycemia and stress Inhibited by rising cortisol levels

Tropic Hormones

Hormones SecretedFollicle Stimulating Hormone (FSH)Not present until pubertyStimulates gamete production and maturation in both males

and femalesRelease stimulated by GnRH Inhibited by rising gonadal hormones

Anterior Pituitary Gland

Hormones SecretedLuteinizing Hormone (LH)Promotes production of gonadal hormonesControlled by the same hormones as FSHTriggers ovulation in females

Non-tropic HormonesHormones Secreted

Growth Hormone (GH) or SomatotropinProduced in response to growth hormone releasing hormone

(GHRH from hypothalamus)Also secreted in response to hypoglycemia or decreased

blood GH or Increased amino acid levels Inhibited by GHIH (somatostatin from hypothalamus)Stimulates cell growth and division in most cells (esp. bone

and muscle)Mobilizes fat to conserve glucoseHyposecretion results in pituitary dwarfismHypersecretion results in gigantism or acromegaly

Non-tropic Hormones

Hormones Secreted Prolactin (PRL)

Release stimulated by PRH

Inhibited by PIH (dopamine)

Both are influenced by estrogen

Stimulates milk production by breasts

Thyroid Gland - Anatomy

The Thyroid Gland

Two lateral lobes Composed of follicles Cuboidal follicle cells produce thyroglobulin

Thyroglobulin stored in lumen of follicle Iodine attaches Molecule is split into T3 and T4 (mostly T4) Hormones enter circulation, more T3 formed

thyroid gland

Thyroid Gland - histology Follicular cells

follicles colloidthyroglobulin

T3 – triiodothyronine

T4 – thyroxine

Parafollicular cellsCalcitonin

Thyroid Gland - hormones Follicular cells

thyroglobulinT3 – triiodothyronineT4 – thyroxine

• + BMR (glucose oxidation)• maintains bp• tissue growth & development

Parafollicular cellsCalcitonin

• decreases blood calcium• + osteoblasts

Thyroid Gland – T3/T4 production

Follicles – colloid, follicular cells Cells make thyroglobulin Thyroglobulin moves into follicle Iodine pumped into follicle Iodine used to make subunits

• 1 OR 2 IODINE

Subunits moved into follicle cells Subunits join to make T3 or T4 T3/T4 released from follicle cells

Thyroid Hormone Production

Thyroid HormoneT4 converted to T3 once in tissuesSecreted in response to TSH Inhibited by rising blood thyroid hormone levelsEffects:

Increases metabolic rate Increases heat productionPromotes protein synthesis and enhances the affect of GHPromotes uptake of glucose by cellsPromotes lipid metabolismSpeeds up actions of nervous system

Thyroid HormoneHyposecretion

Can result in cretinism in children

Myxedema in adults

HypersecretionGrave’s Disease

Thyroglobulin

Thyroid Gland - pathology

Myxedema – adult hypothyroid

Goiter – enlarged thyroid due to lack of iodine

Cretinism – infantile hypothyroid

Grave’s disease – hyperthyroid exophthalmos

Calcitonin

Secreted by parafollicular or C cells by the thyroid

Released in response high blood calcium

Stimulates uptake of calcium by bone

parafollicular cells

Parathyroid Glands4 to 8 on posterior thyroid

glandSecrete Parathyroid Hormone

(PTH)Secreted in response to low

blood calciumStimulates bone resorptionReleased calcium enters blood Increases absorption of calcium

by intestines and reabsorption by kidneys

parathyroid glands

Parathyroid Hormone

Hypersecretion Depletes calcium from bones Depresses nervous system

activity Skeletal muscle weakness

Hyposecretion Over excitability of neurons Muscle spasms Convulsions

Chief cells

Adrenal (Suprarenal) Glands

Two glands--one on top of each kidney

Outer cortex, inner medullaCortex

Produces over 2 dozen corticosteroids from cholesterol

Increased hormone output in response to ACTH or stress

adrenal gland

cortex

medulla

Adrenal Cortex

Three Regions:Zona GlomerulosaOuter regionProduction of

mineralocorticoids (aldosterone)

Regulation of electrolyte & fluid balance

Aldosterone

95% of mineralocorticoidsSodium reabsorption (and water) by kidney

tubulesIncreases blood volume and pressureStimulated by angiotensin

Renin secreted by kidneysActivates angiotensin hormones in bloodStimulates release of aldosterone

Inhibited by Atrial Natriuretic Factor (ANF)Secreted by heart cells when B.P. risesBlocks secretion of renin and aldosterone

Adrenal Cortex

Zona Fasciculata Middle region Secretes glucocorticoids

(cortisol)

Cortisol Released in response to ACTH Inhibited by increased cortisol Promotes gluconeogenesis

(production of glucose from non-carbohydrate sources)

Causes a rise in B.P. Anti-inflammatory if given in

higher doses

CortisolHypersecretion

Cushing’s SyndromeDepressed bone and cartilage formationDepressed inflammatory response and immune

systemEdema, hypertension, loss of muscle and bone,

‘moon face’Hyposecretion

Addison’s diseaseDrop in blood plasma volumeInability to cope with stress or regulate blood sugar

levelsIncreased skin pigmentation

Adrenal Cortex

Zona ReticularisInner regionProduces

glucocorticoids & gonadocorticoids (androgens and estrogen)

ADRENAL MEDULLA

Chromaffin CellsSecrete epinephrine and

norepinephrine (Catecholamines)

Release stimulated by sympathetic neurons

Prolongs the fight or flight response

The PancreasMixed endocrine and

exocrine functionAcinar Cells

Secrete digestive enzymes into small intestine

Islets of LangerhansContain alpha cells Glucagon

Contain beta cells Insulin

Pancreas

endocrine and exocrine Islets of LangerhansCell Types:

Alpha Glucagon Increases blood sugar

Beta Insulin Decreases blood sugar

Delta Somatostatin Inhibit glucagon/insulin releaseInhibit digestive tract activity

PP Pancreatic Polypeptide

Regulates exocrine functionInhibits bile release

InsulinStimulated by high blood

sugar Inhibited by decrease in

blood sugar or somatostatin (GHIH)

Lowers blood sugarEnhances glucose transport

into cells (esp. muscle)Stimulates glycogen

formation Promotes conversion of

glucose to fatStimulates protein

synthesis in muscle Islet of Langerhans

Glucagon Released in response to low

blood sugar Mobilizes fatty acids, glucose

and amino acids from storage Promotes release of fat from

adipose tissue Promotes:

Gluconeogenesis (production of glucose from non-carb. sources)

Glycogenolysis (breakdown of glycogen into glucose)

Raises blood sugar levels

Diabetes

Diabetes InsipidusCaused by ADH deficiency Large quantities of urineDehydration No blood sugar accumulation

Diabetes MellitusResults from Hyposecretion of insulin or hypoactivity of insulin

DiabetesDiabetes Mellitus

Two types:Type 1 (Juvenile Onset)

Usually before age 20 Decreased amount of beta cells in pancreas Possibly autoimmune cause Long term vascular and neural problems

Type 2 (Adult Onset) Insulin is produced but receptors are resistant to it Family tendencies Influenced by weight, diet and exercise

Diabetes

Lack of insulin or response to itInability of glucose to enter body cellsHigh blood sugarFat stores are mobilized for fuelBlood sugar and fatty acid levels rise higherKetone bodies build up from breakdown of fatty acidsKetosis or acidosis results (lowered blood pH)Crisis, coma or death

DiabetesSymptoms

PolyuriaLarge urine output

PolydipsiaExcessive thirst

PolyphagiaExcessive hunger caused by the inability to use glucose as

an energy source

The Pineal Gland

Secretes melatoninMay affect responses to

light cyclesMay inhibit gonad activity

in humans until puberty

“brain sand”

The Thymus GlandShrinks with ageProduces thymopoietin and

thymosinAids in development of the

immune response (development of T- lymphocytes)

THE GONADSProduce gametes and reproductive hormones

Testosterone in malesMaturation of reproductive organsSecondary sex characteristicsSex drive

Estrogens and progesterone in femalesEstrogens cause maturation of reproductive organs and

appearance of secondary sex characteristicsWith progesterone, promote breast development and cyclic

changes in uterine lining