THE ENDOCRINE SYSTEM

D. C. MIKULECKY
PROFESSOR OF PHYSIOLOGY
AND
FACULTY MENTORING PROGRAM
 COMPARISON OF ENDOCRINE
AND NERVOUS SYSTEMS
• NERVOUS SYSTEM • ENDOCRINE SYSTEM
• “WIRED” • “WIRELESS”
• CHEMICAL SIGNAL • CHEMICAL SIGNAL
AT TARGET CELL AT TARGET CELL
• RAPID • SLOW
• BRIEF DURATION • LONG DURATION
• CLOSE ANATOMICAL • SPECIFIC
PROXIMITY RECEPTORS
 CATEGORIES OF
HORMONES
• PEPTIDES

• AMINES

• STEROIDS
 PEPTIDES
• HYDROPHILIC
• DISSOLVED IN PLASMA
• RECEPTOR ON CELL SURFACE
• cAMP OR CALCIUM AS SECOND
MESSENGERS
• ACTIVATE SPECIFIC GENES TO
INITIATE PROTEIN SYNTHESIS
 PEPTIDE HORMONES
• HYPOTHALAMIC
• PITUITARY
• PANREATIC
• PARATHYROID
• GI
• KIDNEY
• LIVER
• HEART
 AMINES
• THYROID HORMONE
• CATECHOLAMINES
• ALL DERIVED FROM AMINO ACID
TYROSINE
• UNIQUE SYNTHETIC AND
SECRETORY PATHWAYS
 STEROIDS
• LIPOPHILIC
• RECEPTOR IN CYTOPLASM
• ACTIVATE SPECIFIC GENES TO
INITIATE PROTEIN SYNTHESIS
• ADRENAL CORTICAL
• GONADAL
• PLACENTAL
 PLASMA CONCENTRATION
OF HORMONES
• DEPENDS ON RATE OF SECRETION
• NEGATIVE FEEDBACK
• NEUROENDOCRINE REFLEXES
• DIURNAL RHYTHMS
 TYPES OF ENDOCRINE
DISORDERS
• HORMONE EXCESS

• HORMONE DEFICIENCY

• DECREASED RESPOSIVENESS OF
RECEPTORS
 HYPOTHALAMUS AND POSTERIOR
PITUITARY
NEUROSECRETORY
NEURONS HYPOTHALAMUS

VASOPRESSIN POSTERIOR
OXYTOCIN PITUITARY

ANTERIOR SYSTEMIC
ARTERY
PITUITARY
SYSTEMIC
VEIN
 HYPOTHALAMUS AND ANTERIOR
PITUITARY
NEUROSECRETORY
NEURONS HYPOTHALAMUS

ANTERIOR
PITUITARY: POSTERIOR
•TSH PITUITARY
•ACTH
•PROLACTIN
•GROWTH
HORMONE
•LH
•FSH
 HYPOTHALAMIC-HYPOPHYSEAL
PORTAL SYSTEM
• VESSELS PASS THROUGH STALK OF
PITUITARY FROM HYPOTHALAMUS
TO ANTERIOR PITUITARY
• CARRY HYPOTHALAMIC
REGULATORY HORMONES
 HYPOTHALAMIC REGULATORY
HORMONES
• TROPIC HORMONES
• CONTROL THE SECRETION OF OTHER
HORMONES BY ACTING ON
ENDOCRINE TISSUE
HYPOTHALAMIC RELEASING AND
INHIBITING HORMONES
• CONTROL THE SECRETION OF ANTERIOR PITUITARY
TROPIC HORMONES
• TRH:THYROTROPIN-RELEASING HORMONE
• PRH:PROLACTIN RELEASING HORMONE
• PIH:PROLACTIN INHIBITING HORMONE
• GHRH:GROWTH HORMONE RELEASING HORMONE
• GHIH: GROWTH HORMONE INHIBITING HORMONE
• CRH:CORTICOTROPHIN RELEASING HORMONE
 HIERARCHICAL CONTROL
INPUT
HYPOTHALAMUS
HORMONE 1 (RELEASING/INHIBITING)
ANTERIOR PITUITARY H/H PORTAL SYSTEM
HORMONE 2 (TROPIC)
ENDOCRINE GLAND SYSTEMIC CIRCULATION
HORMONE 3
SYSTEMIC CIRCULATION
TARGET
CELLS
 NEGATIVE FEEDBACK
INPUT
HYPOTHALAMUS
HORMONE 1 (RELEASING/INHIBITING)
ANTERIOR PITUITARY H/H PORTAL SYSTEM
HORMONE 2 (TROPIC)
ENDOCRINE GLAND SYSTEMIC CIRCULATION
HORMONE 3
SYSTEMIC CIRCULATION
TARGET
CELLS
ANTERIOR PITUITARY HORMONES:TSH

• THYROID GLAND

• THYROID HORMONES (T3 & T4 )

 ANTERIOR PITUITARY
HORMONES:ACTH

• ADRENAL CORTEX

• CORTISOL
 ANTERIOR PITUITARY
HORMONES:PROLACTIN

• MAMMARY GLANDS

• BREAST GROWTH AND MILK

SECRETION
 ANTERIOR PITUITARY HORMONES:
GROWTH HORMONE
• LIVER • MANY TISSUES
• SOMATOMEDINS • INTERMEDIARY
• BONE METABOLISM
• SOFT TISSUE • INCREASE OR
• GROWTH DECREASE
 ANTERIOR PITUITARY HORMONES:
LH & FSH: ACT ON GONADS
• LH:LETEINIZING • FSH:FOLLICLE
HORMONE STIMULATING
HORMONE
• SEX HORMONE • GAMETE
SECRETION PRODUCTION
• F: ESTROGEN AND • OVA
PROGESTERONE • SPERM
• M: TESTOSTERONE
 CONTROL OF GROWTH
• GENETIC
• DIET
• DISEASE
• HORMONES
 ANTERIOR PITUITARY HORMONES:
GROWTH HORMONE
• LIVER • MANY TISSUES
• SOMATOMEDINS • INTERMEDIARY
• BONE METABOLISM
• SOFT TISSUE • INCREASE OR
• GROWTH DECREASE
METABOLIC ACTIONS OF GROWTH
HORMONE
• MOBILIZES TRIGLYCERIDE FAT
STORED IN ADIPOSE TISSUE
• CONSERVES GLUCOSE FOR BRAIN
 GROWTH PROMOTING ACTIONS
OF GROWTH HORMONE
• SOFT TISSUES: STIMULATES CELL
DIVISION, INCREASES SIZE OF CELLS
• STIMULATES ALMOST ALL ASPECTS
OF PROTEIN SYNTHESIS
• INHIBITS PROTEIN DEGRADATION
• PROMOTES UPTAKE OF AMINO
ACIDS
 GROWTH PROMOTING ACTIONS
OF GROWTH HORMONE
• BONE: PROMOTES GROWTH OF LONG
BONES
• THICKNESS
• LENGTH
• AT END OF ADOLESCENCE, SEX
HORMONES STOP THIS ACTION
 GROWTH HORMONE ACTS
THROUGH SOMATOMEDINS
• PEPTIDE MEDIATORS
• PRODUCED IN LIVER AND OTHER
TISSUES
• ALSO PARACRINE EFFECTS
 GHRH AND GHIH
• ANTAGONIST IN CONTROL OF
GROWTH HORMONE SECRETION
• NEGATIVE FEEDBACK
• DIURNAL RHYTHM: GH SECRETED
AT NIGHT
• EXERCISE, STRESS, HYPOGLYCEMIA
ABNORMAL GH SECRETION
• DEFICIENCY: DWARFISM, REDUCED
MUSCLE STRENGTH, DECREASED
BONE DENSITY
• EXCESS:GIGANTISM, ACROMEGLY
 THE THYROID GLAND
• OVER TRACHEA
• THYROGLOBULIN
• TETRAIODOTHYRONINE
• TRIIODOTHYRONINE
• IODINE REQUIRED FROM DIETARY
INTAKE
 THYROID HORMONE’S EFFECTS

• METABOLIC RATE: INCREASED BMR

• CALOROGENIC: INCREASED HEAT PRODUCTION
• SYMPATHOMIMETIC: FLIGHT OR FIGHT
• CARDIOVASCULAR:INCREASES RESPONSIVENESS
OF HEART
• GROWTH: ESSENTIAL FOR NORMAL GROWTH
• NERVOUS SYSTEM:DEVELOPMENT AND ADULT
ACTIVITY
 REGULATION OF THYROID
SECRETION
COLD IN
STRESS HYPOTHALAMUS
CHILDREN
- TRH
+

ANTERIOR PITUITARY

TSH

THYROID GLAND
THYROID HORMONE
TARGET ORGANS
 ABNORMALITIES OF THYROID
FUNCTION
• HYPO • HYPER
• REDUCED BMR
• POOR TOLERANCE OF COLD • GRAVE’S
• GAIN OF WEIGHT DISEASE:TSI
• FATIGUE
• EXOPHTALMOS
• SLOW, WEAK PULSE
• SLOW REFLEXES AND • GOITER
MENTATION
• MYXEDEMA
• GOITER
• CRETINISM
 THE ADRENAL GLANDS
• CORTEX: STEROID HORMONES
SECRETED

• MEDULLA: CATECHOLAMINES
 CORTEX: STEROID
HORMONES SECRETED
• MINERALOCORTICOIDS

• GLUCOCORTICOIDS

• SEX HOMONES
 MINERALOCORTICOIDS
• ALDOSTERONE
• ELECTROLYTE BALANCE
• BLOOD PRESSURE
• RENIN-ANGIOTENSIN-ALDOSTERONE
SYSTEM
 GLUCOCORTICOIDS
• CORTISOL
• GLOCONEOGENESIS
• PERMISSIVE ACTIONS
• STRESS ADAPTATION
• ANTI-INFLAMITORY AND
IMMUNOSUPPRESSANT
 REGULATION OF CORTISOL
SECRETION
DIURNAL
STRESS HYPOTHALAMUS
RHYTHM
+ - +
CRH

ANTERIOR PITUITARY
INCREASED
BLOOD GLUCOSE ACTH -
BLOOD AA
BLOOD FATTY ACIDS
ADRENAL CORTEX
CORTISOL
TARGET ORGANS
 SEX HOMONES
• ANDROGENS (TESTOSTERONE)

• ESTROGENS

• LESS THAN GONADS

ADRENAL OVERSECRETION
• MINERALCORTICOIDS: SODIUM
RETENTION, POTASSIUM DEPLETION
• CORTISOL:EXCESS GLUCONEOGENESIS-
EXCESS GLUCOSE DEPOSITED AS FAT
• ANDROGEN:MASCULINIZATION,
PSEUDOHERMAPHODITISM, PRECOCIOUS
PSEUDOPUBERTY, NO EFFECT IN
ADULT MALES
 ADRENAL INSUFFICIENY
• CORTEX: ADDISON’S DISEASE
• POOR RESPONSE TO STRESS
• LACK OF PERMISSIVE ACTION
• POTASSIUM RETENTION
• HYPOTENSION
MEDULLA: CATECHOLAMINES
• A MODIFIED SYMPATHETIC POST
GANGLIONIC NEURON
• EPINEPHRINE
 ACTIONS OF EPINEPHRINE
• MIMICS SYMPATHETIC NS
• MOBILIZES STORED FAT AND
CARBOHYDRATE
• HEART AND BLOOD VESSELS
 GENERAL ADAPTATION
SYNDROME
• FLIGHT OR FIGHT
• EPINEPHRINE
• CRH-ACTH-CORTISOL
• RENIN-ANGIOTENSIN-ALDOSTERONE
• VASOPRESSIN
• COORDINATED BY HYPOTHALAMUS
• CAN BE INDUCED PSYCHOSOCIALLY
 CONTROL OF FUEL
METABOLISM
• GLYCOGENESIS
• GLYCOGENOLYSIS
• GLUCONEOGENESIS
• PROTEIN SYNTHESIS
• PROTEIN DEGRADATION
• FAT SYNTHESIS
• FAT BREAKDOWN
ANABOLISM VS CATABOLISM

• BUILD UP VS BREAKDOWN OF
LARGE MOLECULES
• ANABOLISM REQUIRES ENERGY
(ATP)
• CATABOLISM:ENERGY PRODUCTION
 PANCREATIC HORMONES
• INSULIN

• GLUCAGON
 INSULIN: ACTION ON BLOOD
SUGAR
• BETA CELLS IN ISLETS OF
LANGERHANS: INSULIN
• FACILITIES GLUCOSE ENTRY INTO
CELLS
• STIMULATES GLYCOGENESIS
• INHIBITS GLYCOGENOLYSIS
• INHIBITS GLUCONEOGENESIS
 INSULIN: ACTION ON FAT
• INCREASES TRANSPORT INTO
ADIPOSE CELLS
• PROMTES TRIGLYCERIDE SYNTHESIS
• INHIBITS LIPOLYSIS
INSULIN: ACTION ON PROTEIN

• PROMOTES UPTAKE OF AA BY
MUSCLE AND OTHER TISSUE
• PROMOTES PROTEIN SYNTHESIS
• INHIBITS PROTEIN DEGRADATION
CONTROL OF INSULIN SECRETION

• NEGATIVE FEEDBACK: BLOOD

SUGAR
• BLOOD AA
• GI HORMONES
• PARASYMPATHETIC ACTIVITY
 TWO TYPES OF DIABETES
MELLITUS
• TYPE I: AUTOIMMUNE
DESTRUCTION OF BETA CELLS,
LACK OF INSULIN SECRETION
• TYPE II: REDUCED SENSITIVITY OF
INSULIN RECEPTORS
 ACUTE EFFECTS OF DIABETES
MELLITUS
• EXTRACELLULAR GLUCOSE EXCESS
• GLUCOSE IN URINE
• EXCESS FLUID LOSS
• CIRCULATORY FAILURE
• RENAL FAILURE
• NERVOUS SYSTEM MALFUNCTION DUE TO DEHYDRATION
• EXCESSIVE FOOD INTAKE
• PROGRESSIVE WEIGHT LOSS
• MOBILIZTION OF FAT
• KETOSIS
• ACIDOSIS
• COMA AND DEATH
 GLUCAGON
• PANCREATIC ALPHA CELLS
• GENERALLY OPPOSES ACTIONS OF
INSULIN
• DECREASE GLYCOGEN SYNTHESIS
• PROMOTE GLYCOGENOLYSIS
• STIMULATE GLUCONEOGENESIS
• PROMOTES FAT BREAKDOWN
• ONLY IN LIVER: PROTEIN CATABOLISM
 EPINEPHRINE, CORTISOL, AND
GROWTH HORMONE
• ALL INCREASE BLOOD GLUCOSE
AND FATTY ACIDS
• CORTISOL INCREASES BLOOD AA
AND DECREASES MUSCLE PROTEIN
• GH DECREASES BLOOD AA AND
INCREASES MUSCLE PROTEIN
 CONTROL OF CALCIUM
METABOLISM
• PARATHYROID HORMONE
• CALCITONIN
• VITAMIN D
 PARATHYROID HORMONE
• RAISES FREE PLASMA CALCIUM
• FROM BONE
• CONSERVATION IN KIDNEYS
• INCREASES INTESTINAL ABSORPTION (VIA
VITAMIN D ACTIVATION)
• REGULATED BY FREE CALCIUM IN
PLASMA (NEGATIVE FEEDBACK)
 CALCITONIN
• C CELLS OF THYROID GLAND
• DECREASE IN CA MOBILIZATION
FROM BONE
• NOT AS IMPORTANT AS PTH AND
VITAMIN D
 VITAMIN D
• ACTUALLY A HORMONE
• RELEASED FROM SKIN BY SUNLIGHT
• TWO STEP ACTIVATION: LIVER AND
KIDNEYS
• INCREASES CALCIUM ABSORPTION
IN INTESTINE
 PTH HYPOSECRETION
• LOW CALCIUM AND HIGH
PHOSPHATE
• MUSCLE SPASMS
• MENTAL CHANGES
 VITAMIN D DEFICIENCY
• IMPARED ABSORPTION OF CALCIUM
• PTH MAINTAINS PLASMA LEVEL AT
EXPENSE OF BONES
• RICKETS IN CHILDREN
• OSTEOMALACIA IN ADULTS