Endocrine SystemEndocrine SystemA. Endocrine glandsA. Endocrine glandsB. Comparison of nervous and endocrineB. Comparison of nervous and endocrine systemssystemsC. HormonesC. Hormones

1. Hormone receptors1. Hormone receptors 2. Circulating and local hormones2. Circulating and local hormones

D. Mechanisms of hormone actionD. Mechanisms of hormone action 1. Activation of intracellular receptors1. Activation of intracellular receptors 2. Activation of plasma membrane 2. Activation of plasma membrane

receptorsreceptorsE. Control of hormonal secretionsE. Control of hormonal secretionsF. Hypothalamus and pituitary glandF. Hypothalamus and pituitary gland

(hypophysis)(hypophysis) 1. Anterior pituitary gland 1. Anterior pituitary gland

(adenohypophysis)(adenohypophysis) a. Human growth hormonea. Human growth hormone b. Thyroid-stimulating hormoneb. Thyroid-stimulating hormone c. Follicle-stimulating hormone c. Follicle-stimulating hormone

d. Luteinizing hormoned. Luteinizing hormone e. Prolactine. Prolactin f. Melanocyte-stimulating f. Melanocyte-stimulating

hormonehormone g. Adrenocorticotropic g. Adrenocorticotropic

hormonehormone

2. Posterior pituitary gland2. Posterior pituitary gland (neurohypophysis)(neurohypophysis) a. Oxytocina. Oxytocin b. Antidiuretic hormoneb. Antidiuretic hormone

G. Thyroid glandG. Thyroid gland 1. Formation, storage, and release of1. Formation, storage, and release of thyroid hormonesthyroid hormones 2. Actions of thyroid hormones2. Actions of thyroid hormones 3. Control of thyroid hormone 3. Control of thyroid hormone

secretionsecretion 4. Calcitonin4. Calcitonin

H. Parathyroid glandsH. Parathyroid glands 1. Parathyroid hormone1. Parathyroid hormone

I. Adrenal (suprarenal) glandsI. Adrenal (suprarenal) glands 1. Adrenal cortex1. Adrenal cortex a. Mineralocorticoidsa. Mineralocorticoids b. Glucocorticoidsb. Glucocorticoids c. Gonadocorticoidsc. Gonadocorticoids 2. Adrenal medulla2. Adrenal medulla a. Epinephrine and norepinephrinea. Epinephrine and norepinephrine

J. PancreasJ. Pancreas 1. Glucagon1. Glucagon 2. Insulin2. Insulin

K. General adaptation syndromeK. General adaptation syndrome

Endocrine vs. exocrine

Hormone

Endocrine gland

Endocrine Glands

Together, the nervous and endocrine systems coordinate functions of all body systems.

Nervous System Versus Endocrine System

NERVOUS

neurotransmitters hormones

ENDOCRINE

muscle contractions and glandular secretions

metabolic activities of cells

acts in milliseconds acts in seconds to minutes to hours to days to months

brief effects long-lasting effects

Hormone ReceptorsHormone Receptors

1. 1. target cellstarget cells

2. receptors2. receptors

3. down-regulation3. down-regulation

4. up-regulation4. up-regulation

Hormone InteractionsHormone Interactions

1.1. synergistic effectssynergistic effects

2. permissive effects2. permissive effects

3. antagonistic effects3. antagonistic effects

Types of HormonesTypes of Hormones1. circulating -- hormones1. circulating -- hormones

2. local – paracrines, autocrines2. local – paracrines, autocrines

Mechanisms of Hormone ActionMechanisms of Hormone Action

1. lipid-soluble hormones1. lipid-soluble hormones a. steroid and thyroid hormonesa. steroid and thyroid hormones b. use intracellular receptorsb. use intracellular receptors

2. water-soluble hormones2. water-soluble hormones a. catecholamine, peptide, and a. catecholamine, peptide, and

protein hormonesprotein hormones b. use membrane-bound receptors b. use membrane-bound receptors c. and second messengersc. and second messengers

Lipid Soluble HormonesLipid Soluble Hormones

1. intracelluar receptors1. intracelluar receptors

2. hormone-receptor complex2. hormone-receptor complex

3. altered gene expression3. altered gene expression

Steroid Hormone ActionSteroid Hormone Action

Water Soluble HormonesWater Soluble Hormones

1. membrane-bound receptors1. membrane-bound receptors

2. first messenger 2. first messenger vsvs second second messengermessenger

3. adenylate cyclase and cyclic 3. adenylate cyclase and cyclic AMPAMP

4. phosphodiesterase4. phosphodiesterase

Water soluble hormones and Water soluble hormones and Cyclin AMP as a 2Cyclin AMP as a 2ndnd Messenger Messenger

22ndnd Messenger Systems Messenger Systems

Control of hormonal secretions = Control of hormonal secretions = negative feedbacknegative feedback

time

[glucose]

110 mg%

90 mg%

steady state

hyperglycemia = insulin secretion

hypoglycemia = glucagon secretion

Hypothalamus and Pituitary Hypothalamus and Pituitary GlandGland

HypothalamusHypothalamus

1. master control1. master control

2. major integrator2. major integrator

Pituitary gland (hypophysis)Pituitary gland (hypophysis)

1. infundibulum1. infundibulum

2. sella turcica2. sella turcica

hypothalamus

infundibulum

pituitary gland

sella turcica in sphenoid bone

Hypothalamus-Master ControllerHypothalamus-Master Controller

Pituitary GlandPituitary Gland

1. anterior pituitary1. anterior pituitary a. derived from Rathke's poucha. derived from Rathke's pouch b. connected to hypothalamusb. connected to hypothalamus by hypophyseal portal systemby hypophyseal portal system

2. posterior pituitary2. posterior pituitary a. outgrowth of hypothalamusa. outgrowth of hypothalamus b. contains pituicytesb. contains pituicytes c. connected to hypothalamusc. connected to hypothalamus by nerve tractby nerve tract

(Rathke’s pouch)

Anterior Pituitary Anterior Pituitary (adenohypophysis)(adenohypophysis)

1. releasing vs inhibiting 1. releasing vs inhibiting factorsfactors

2. hypophyseal portal system2. hypophyseal portal system superior hypophyseal arteriessuperior hypophyseal arteries

primary plexus of capillariesprimary plexus of capillaries

hypophyseal veinshypophyseal veins

secondary plexus of secondary plexus of capillariescapillaries

anterior hypophyseal veinsanterior hypophyseal veins

The seven hormones secreted by The seven hormones secreted by the anterior pituitary glandthe anterior pituitary gland

growth hormone (GH)growth hormone (GH)

thyroid-stimulating hormone (TSH)thyroid-stimulating hormone (TSH)

follicle-stimulating hormone (FSH)follicle-stimulating hormone (FSH)

luteinizing hormone (LH)luteinizing hormone (LH)

adrenocorticotropic hormone (ACTH)adrenocorticotropic hormone (ACTH)

prolactin (PRL)prolactin (PRL)

melanocyte-stimulating hormone (MSH)melanocyte-stimulating hormone (MSH)

Tropic HormonesTropic Hormones

FSHFSH

LHLH

TSHTSH

ACTHACTH

Promotion of secretion

Growth Hormone

1. HYPOGLYCEMIA (low blood sugar)

2. decreased blood fatty acids3. increased blood amino acids4. deep sleep

Inhibition of secretion1. HYPERGLYCEMIA (high blood

sugar)

2. increased blood fatty acids3. decreased blood amino acids4. REM sleep5. obesity6. severe emotional states

Actions 1. increased cellular uptake of amino acids = increased protein synthesis = growth/maintenance2. increased lipolysis and gluconeogenesis for energy, leading to hyperglycemia = diabetogenic effect

Regulation of secretion

inhibits GH-IFsecretion

Inhibits GH-RF secretion

HYPOTHALAMUS

hypoglycemia hyperglycemia

GH-RF GH-IF

ANTERIOR PITUITARY GLAND

growth hormone

secretion on secretion off

Growth Hormone AcromegalyGrowth Hormone Acromegaly

Thyroid Stimulating Hormone

decreased basal metabolic rate (BMR)

increased hypothalamic TSH-RF secretion

increased anterior pituitary TSH secretion

increased thyroid gland T3 and T4 secretion

increased basal metabolic rate

negative feedback

( -)

Follicle Stimulating Hormone - male

decreased inhibin secretion

increased hypothalamic Gonadotropin-RF secretion

increased anterior pituitary FSH secretion

1. increased sperm formation (spermatogenesis)2. increased activity of Sertoli cells (spermiogenesis)3. increased inhibin secretion by Sertoli cells

negative feedback of inhibin

( -)

Follicle Stimulating Hormone-Female

decreased estrogen secretion

increased hypothalamic Gonadotropin-RF secretion

increased anterior pituitary FSH secretion

1. directly stimulates egg formation by ovaries2. as a result, ovaries produce estrogen

negative feedback of rising estrogen

( -)

Luteinizing Hormone- male

decreased testosterone secretion

increased hypothalamic Gonadotropin-RF secretion

increased anterior pituitary LH secretion

negative feedback of rising estrogen

( -)

stimulates testosterone secretion by interstitial cells (of Leydig) in testes

Luteinizing Hormone- female

increased estrogen secretion

increased hypothalamic Gonadotropin-RF secretion

increased anterior pituitary LH secretion

negative feedback of

dropping estrogen

( -)

1. directly stimulates ovulation2. as a result, estrogen levels drop

until corpus luteum is formed

Adrenocorticotropic Hormone

increased stress

increased hypothalamic Corticotropin-RF secretion

increased anterior pituitary ACTH secretionnegative

feedback of decreasing

stress

( -)

1. increased alertness 2. increased blood pressure3. increased blood glucose4. anti-inflammatory actions

decreased stress

Prolactin-Female

increased blood estrogen

hypothalamic PRL-IF secretion

decreased or no PRL secretion from anterior pituitary gland

inhibition pathway

milk synthesis by postpartum mammary glands

stimulation pathway

decreased blood estrogen+

postpartum suckling reflex

hypothalamic PRL-RF secretion

anterior pituitary glandPRL secretion

Posterior Pituitary Posterior Pituitary (neurohypophysis)(neurohypophysis)

1. not really endocrine1. not really endocrine2. pituicytes2. pituicytes3. hypothalamic nuclei3. hypothalamic nuclei4. hypothalamo-4. hypothalamo-

hypophyseal tracthypophyseal tract5. hormones5. hormones

a. oxytocina. oxytocin b. antidiuretic hormoneb. antidiuretic hormone

OxytocinOxytocin

1. neuroendocrine reflex1. neuroendocrine reflex

2. uterine contractions2. uterine contractions

3. myoepithelial cells3. myoepithelial cells

of mammary glandsof mammary glands

ANTI-DIURETIC HORMONE1. aka = vasopressin, ADH2. hypothalamic osmoreceptors3. water reabsorption by kidneys4. diabetes insipidus

dehydration

increased interstitial fluid osmotic pressure

stimulation of hypothalamic osmoreceptors( -)

1. WATER REABSORPTION BY KIDNEYS2. decreased perspiration

secretion of ADH from posterior pituitary gland

increased water in blood

increased interstitial fluid osmotic pressure

Also leads to increase in BP

ADH actionsADH actions

Thyroid GlandThyroid Gland1. location1. location2. follicles2. follicles3. follicular cells3. follicular cells4. triiodothyronine (T3)4. triiodothyronine (T3)5. tetraiodothyronine 5. tetraiodothyronine

(T4, thyroxine)(T4, thyroxine)__________________________________________

6. parafollicular (C-) cells6. parafollicular (C-) cells7. calcitonin7. calcitonin

Thyroid Hormone SecretionThyroid Hormone Secretion

1. stores secretory product1. stores secretory product

2. captures iodide ions2. captures iodide ions

3. thyroglobulin3. thyroglobulin

4. tyrosine4. tyrosine

5. colloid5. colloid

thyroglobulin

tyrosine

blood capillary

colloid

follicle cellthyroid follicle

1

2

II

II

I

I

I iodinated tyrosines on thyroglobulin (T3)

colloid

3 thyroid hormone secretion

colloidI

I

II

I

Ipinocytosiscleavage

T3

T3

parafollicular cellsblood

capillary

colloid

follicular cell

Thyroid Hormone Synthesis, Thyroid Hormone Synthesis, Storage and SecretionStorage and Secretion

Endemic Goiter- Iodine deficiency-Endemic Goiter- Iodine deficiency-lack of thryoid hormonelack of thryoid hormone

Thyroxine Actions and ControlThyroxine Actions and Control

1. TSH stimulation1. TSH stimulation2. actions2. actions

a. increased carbohydrate catabolisma. increased carbohydrate catabolism b. increased fat catabolismb. increased fat catabolism c. increased protein anabolismc. increased protein anabolism d. net result = increased BMRd. net result = increased BMR

____________________________________________________________________3. normal growth and development3. normal growth and development

(nervous system -- cretinism)(nervous system -- cretinism)

Thyroxine

decreased basal metabolic rate

increased TSH-RF secretion from hypothalamic neurons

secretion of TSH from anterior pituitary gland( -)

Increased carbohydrate catabolismIncreased fat catabolismIncreased protein anabolism

secretion of T3 and T4 (thyroxine) from thyroid gland follicle cells

T3 and T4 (thyroxine) secretion

increased basal metabolic rate

( -)

negative feedback

Negative Feedback Inhibition in Negative Feedback Inhibition in Pituitary Thryoid AxisPituitary Thryoid Axis

CalcitoninCalcitonin

1. parafollicular (C-) cells1. parafollicular (C-) cells

2. hypercalcemia = CT secretion2. hypercalcemia = CT secretion

3. actions3. actions

a. inhibits osteoclastsa. inhibits osteoclasts

b. stimulates osteogenesisb. stimulates osteogenesis

c. decreased Ca++ reabsorptionc. decreased Ca++ reabsorption

4. result = normocalcemia4. result = normocalcemia

CALCITONIN and BLOOD CALCIUM REGULATION

CONTROLLED CONDITION

RECEPTOR

RETURN TO HOMEOSTASIS

EFFECTORS

CONTROL CENTER

Normocalcemia(blood calcium = 9.5-10.5mg%)

A stress or stimulus causes an increase in blood calcium

Parafollicular cells of thyroid gland recognize hypercalcemia

(blood calcium >10.5 mg%

Parafollicular cells secrete calcitonin

Reduced osteoclast activity

Increased osteoblast activity

Increased bone formation results in increased calcium deposition in bone –

Return to normocalcemia

negative feedback

Parathyroid HormoneParathyroid Hormone

1. location1. location2. chief cells and oxyphil cells2. chief cells and oxyphil cells3. hypocalcemia = PTH secretion3. hypocalcemia = PTH secretion4. actions4. actions

a. activate osteoclastsa. activate osteoclasts b. increased Ca++ absorptionb. increased Ca++ absorption c. increased Ca++ reabsorptionc. increased Ca++ reabsorption

5. result = normocalcemia5. result = normocalcemia

PTH and BLOOD CALCIUM REGULATION

CONTROLLED CONDITION

RECEPTOR

RETURN TO HOMEOSTASIS

EFFECTORS

CONTROL CENTER

Normocalcemia(blood calcium = 9.5-10.5mg%)

A stress or stimulus causes a decrease in blood calcium

Chief cells of parathythyroid glands recognize hypocalcemia

(blood calcium <9.5 mg%

Chief cells secrete PTH

Increased osteoclast activity

Decreased osteoblast activity

Increased urine phosphate output

Decreased urine calcium output

Increased bone breakdown results in increased calcium release to blood –

Return to normocalcemia

negative feedback

Adrenal (suprarenal) glands (2)Adrenal (suprarenal) glands (2)

1. location1. location

2. cortex vs medulla2. cortex vs medulla

3. cortex = steroids3. cortex = steroids

4. medulla = catecholamines4. medulla = catecholamines

a. sympathetic NSa. sympathetic NS

b. NE and EPIb. NE and EPI

c. fight-or-flightc. fight-or-flight

Adrenal cortex (zona Adrenal cortex (zona glomerulosa)glomerulosa)

1. mineralocorticoids (aldosterone)1. mineralocorticoids (aldosterone)2. electrolyte and fluid balance2. electrolyte and fluid balance3. high [K+] = aldosterone secretion3. high [K+] = aldosterone secretion

oror renin-angiotensin systemrenin-angiotensin system

4. actions4. actions a. decreased K+ reabsorptiona. decreased K+ reabsorption b. increased Na+ reabsorptionb. increased Na+ reabsorption

Aldosterone

hyperkalemia

aldosterone secretion from zona glomerulosa cells

decreased K+ reabsorption by kidneys

normokalemia

( -)

negative feedback

control via potassium control via renin-angiotensin system

dehydration, Na+ deficiency, hemorrhage

decreased blood volume

decreased blood pressure

renin secretion by kidneys

( -)

negative feedback

activation of angiotensin II

aldosterone secretionADH secretionincreased thirstincreased vasoconstriction

increased blood pressure

Adrenal cortex (zona fasciculata)Adrenal cortex (zona fasciculata)

1. glucocorticoids (hydrocortisone, cortisone)1. glucocorticoids (hydrocortisone, cortisone)

2. stress > C-RF > ACTH > glucocorticoids2. stress > C-RF > ACTH > glucocorticoids

3. actions3. actions

a. promote normal metabolism (glucose a. promote normal metabolism (glucose availability)availability)

b. resistance to stress (alertness, energy, b. resistance to stress (alertness, energy, blood pressure)blood pressure)

c. anti-inflammatory (stabilizes c. anti-inflammatory (stabilizes membranes)membranes)

Glucocorticoidsincreased stress or decreased blood levels of glucocorticoids

increased hypothalamic corticotropin-RF secretion

increased anterior pituitary ACTH secretion

increased adrenal secretion of glucocorticoids

( -)

negative feedback

promote normal metabolism and ensure glucose availability by: increasing protein catabolism increasing gluconeogenesis increased lipolysisProvide resistance to stress by: increased mental alertness increased energy increased blood pressureIncreasing anti-inflammatory activity by: stabilizing cell membranes depressing phagocyte activity decreased capillary permeability (decreased swelling)

decreased stress

( -)

negative feedback

Adrenal cortex (zona reticularis)Adrenal cortex (zona reticularis)

1. gonadocorticoids1. gonadocorticoids

a. androgensa. androgens

b. estrogensb. estrogens

2. important in development2. important in development

Endocrine (pancreas)Endocrine (pancreas)

1. location1. location2. islets of Langerhans2. islets of Langerhans3. cell types3. cell types

a. alpha cells = glucagona. alpha cells = glucagon b. beta cells = insulinb. beta cells = insulin c. delta cells = c. delta cells = somatostatin (GH-IF)somatostatin (GH-IF) d. F cells = digestiond. F cells = digestion

Glucagon

hypoglycemia (<90mg%)

alpha cells secrete glucagon

liver cells: increase glycogenolysis increased gluconeogenesis

normoglycemia (>90mg%)

( -)

negative feedback

increased blood glucose

1. alpha cells2. hypoglycemia > glucagon secretion3. actions a. glycogenolysis b. gluconeogenesis4. result = normoglycemia

Insulin

hyperglycemia (<110mg%)

beta cells secrete insulin

increased glucose uptake into body cells increase glycogenesis (skeletal muscle, liver)increased lipogenesis

normoglycemia (<110mg%)

( -)

negative feedback

decreased blood glucose

1. beta cells2. hyperglycemia > insulin secretion3. activities a. glucose uptake b. glycogenesis c. glycogenolysis d. gluconeogenesis e. lipogenesis4. result = normoglycemia______________________diabetes mellitus

GENERAL ADAPTATION SYNDROME

ALARM

RESISTANCE

EXHAUSTION

STRESS

hypothalamus

C-RF secretion increased sympathetic activity increased blood pressure

ACTH norepinephrineepinephrine

---------------------------------------------------------------------------------------------------------------------------------

glucocorticoids increased blood pressure continued

decreased inflammatory responseincreased blood glucosealtered protein and fat metaoblism

---------------------------------------------------------------------------------------------------------------------------------

decreased immune response + decreased energy reserves

decreased resistance to disease

hypertension

cardiac failure and renal failure

DEATH