THE ENDOCRINE SYSTEM

1
THE ENDOCRINE SYSTEM

• D. C. MIKULECKY
• PROFESSOR OF PHYSIOLOGY
• AND
• FACULTY MENTORING PROGRAM

2
COMPARISON OF ENDOCRINE AND NERVOUS SYSTEMS

• NERVOUS SYSTEM
• WIRED
• CHEMICAL SIGNAL AT TARGET CELL
• RAPID
• BRIEF DURATION
• CLOSE ANATOMICAL PROXIMITY

• ENDOCRINE SYSTEM
• WIRELESS
• CHEMICAL SIGNAL AT TARGET CELL
• SLOW
• LONG DURATION
• SPECIFIC RECEPTORS

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CATEGORIES OF HORMONES

• PEPTIDES
• AMINES
• STEROIDS

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PEPTIDES

• HYDROPHILIC
• DISSOLVED IN PLASMA
• RECEPTOR ON CELL SURFACE
• cAMP OR CALCIUM AS SECOND MESSENGERS
• ACTIVATE SPECIFIC GENES TO INITIATE PROTEIN
  SYNTHESIS

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PEPTIDE HORMONES

• HYPOTHALAMIC
• PITUITARY
• PANREATIC
• PARATHYROID
• GI
• KIDNEY
• LIVER
• HEART

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AMINES

• THYROID HORMONE
• CATECHOLAMINES
• ALL DERIVED FROM AMINO ACID TYROSINE
• UNIQUE SYNTHETIC AND SECRETORY PATHWAYS

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STEROIDS

• LIPOPHILIC
• RECEPTOR IN CYTOPLASM
• ACTIVATE SPECIFIC GENES TO INITIATE PROTEIN
  SYNTHESIS
• ADRENAL CORTICAL
• GONADAL
• PLACENTAL

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PLASMA CONCENTRATION OF HORMONES

• DEPENDS ON RATE OF SECRETION
• NEGATIVE FEEDBACK
• NEUROENDOCRINE REFLEXES
• DIURNAL RHYTHMS

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TYPES OF ENDOCRINE DISORDERS

• HORMONE EXCESS
• HORMONE DEFICIENCY
• DECREASED RESPOSIVENESS OF RECEPTORS

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HYPOTHALAMUS AND POSTERIOR PITUITARY
NEUROSECRETORY NEURONS
HYPOTHALAMUS
VASOPRESSIN
POSTERIOR PITUITARY
OXYTOCIN
ANTERIOR PITUITARY
SYSTEMIC ARTERY
SYSTEMIC VEIN
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HYPOTHALAMUS AND ANTERIOR PITUITARY
NEUROSECRETORY NEURONS
HYPOTHALAMUS

• ANTERIOR
• PITUITARY
• TSH
• ACTH
• PROLACTIN
• GROWTH
• HORMONE
• LH
• FSH

POSTERIOR PITUITARY
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HYPOTHALAMIC-HYPOPHYSEAL PORTAL SYSTEM

• VESSELS PASS THROUGH STALK OF PITUITARY FROM
  HYPOTHALAMUS TO ANTERIOR PITUITARY
• CARRY HYPOTHALAMIC REGULATORY HORMONES

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HYPOTHALAMIC REGULATORY HORMONES

• TROPIC HORMONES
• CONTROL THE SECRETION OF OTHER HORMONES BY ACTING
  ON ENDOCRINE TISSUE

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HYPOTHALAMIC RELEASING AND INHIBITING HORMONES

• CONTROL THE SECRETION OF ANTERIOR PITUITARY
  TROPIC HORMONES
• TRHTHYROTROPIN-RELEASING HORMONE
• PRHPROLACTIN RELEASING HORMONE
• PIHPROLACTIN INHIBITING HORMONE
• GHRHGROWTH HORMONE RELEASING HORMONE
• GHIH GROWTH HORMONE INHIBITING HORMONE
• CRHCORTICOTROPHIN RELEASING HORMONE

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HIERARCHICAL CONTROL
INPUT
HYPOTHALAMUS
HORMONE 1 (RELEASING/INHIBITING)
H/H PORTAL SYSTEM
ANTERIOR PITUITARY
HORMONE 2 (TROPIC)
SYSTEMIC CIRCULATION
ENDOCRINE GLAND
HORMONE 3
SYSTEMIC CIRCULATION
TARGET CELLS
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NEGATIVE FEEDBACK
INPUT
HYPOTHALAMUS
HORMONE 1 (RELEASING/INHIBITING)
H/H PORTAL SYSTEM
ANTERIOR PITUITARY
HORMONE 2 (TROPIC)
SYSTEMIC CIRCULATION
ENDOCRINE GLAND
HORMONE 3
SYSTEMIC CIRCULATION
TARGET CELLS
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ANTERIOR PITUITARY HORMONESTSH

• THYROID GLAND
• THYROID HORMONES (T3 T4 )

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ANTERIOR PITUITARY HORMONESACTH

• ADRENAL CORTEX
• CORTISOL

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ANTERIOR PITUITARY HORMONESPROLACTIN

• MAMMARY GLANDS
• BREAST GROWTH AND MILK SECRETION

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ANTERIOR PITUITARY HORMONES GROWTH HORMONE

• LIVER
• SOMATOMEDINS
• BONE
• SOFT TISSUE
• GROWTH

• MANY TISSUES
• INTERMEDIARY METABOLISM
• INCREASE OR DECREASE

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ANTERIOR PITUITARY HORMONESLH FSH ACT ON
GONADS

• LHLETEINIZING HORMONE
• SEX HORMONE SECRETION
• F ESTROGEN AND PROGESTERONE
• M TESTOSTERONE

• FSHFOLLICLE STIMULATING HORMONE
• GAMETE PRODUCTION
• OVA
• SPERM

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CONTROL OF GROWTH

• GENETIC
• DIET
• DISEASE
• HORMONES

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ANTERIOR PITUITARY HORMONES GROWTH HORMONE

• LIVER
• SOMATOMEDINS
• BONE
• SOFT TISSUE
• GROWTH

• MANY TISSUES
• INTERMEDIARY METABOLISM
• INCREASE OR DECREASE

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METABOLIC ACTIONS OF GROWTH HORMONE

• MOBILIZES TRIGLYCERIDE FAT STORED IN ADIPOSE
  TISSUE
• CONSERVES GLUCOSE FOR BRAIN

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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

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GROWTH PROMOTING ACTIONS OF GROWTH HORMONE

• BONE PROMOTES GROWTH OF LONG BONES
• THICKNESS
• LENGTH
• AT END OF ADOLESCENCE, SEX HORMONES STOP THIS
  ACTION

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GROWTH HORMONE ACTS THROUGH SOMATOMEDINS

• PEPTIDE MEDIATORS
• PRODUCED IN LIVER AND OTHER TISSUES
• ALSO PARACRINE EFFECTS

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GHRH AND GHIH

• ANTAGONIST IN CONTROL OF GROWTH HORMONE SECRETION
• NEGATIVE FEEDBACK
• DIURNAL RHYTHM GH SECRETED AT NIGHT
• EXERCISE, STRESS, HYPOGLYCEMIA

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ABNORMAL GH SECRETION

• DEFICIENCY DWARFISM, REDUCED MUSCLE STRENGTH,
  DECREASED BONE DENSITY
• EXCESSGIGANTISM, ACROMEGLY

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THE THYROID GLAND

• OVER TRACHEA
• THYROGLOBULIN
• TETRAIODOTHYRONINE
• TRIIODOTHYRONINE
• IODINE REQUIRED FROM DIETARY INTAKE

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THYROID HORMONES EFFECTS

• METABOLIC RATE INCREASED BMR
• CALOROGENIC INCREASED HEAT PRODUCTION
• SYMPATHOMIMETIC FLIGHT OR FIGHT
• CARDIOVASCULARINCREASES RESPONSIVENESS OF HEART
• GROWTH ESSENTIAL FOR NORMAL GROWTH
• NERVOUS SYSTEMDEVELOPMENT AND ADULT ACTIVITY

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REGULATION OF THYROID SECRETION
COLD IN CHILDREN
HYPOTHALAMUS
STRESS
-

TRH
ANTERIOR PITUITARY
TSH
THYROID GLAND
THYROID HORMONE
TARGET ORGANS
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ABNORMALITIES OF THYROID FUNCTION

• HYPO
• REDUCED BMR
• POOR TOLERANCE OF COLD
• GAIN OF WEIGHT
• FATIGUE
• SLOW, WEAK PULSE
• SLOW REFLEXES AND MENTATION
• MYXEDEMA
• GOITER
• CRETINISM

• HYPER
• GRAVES DISEASETSI
• EXOPHTALMOS
• GOITER

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THE ADRENAL GLANDS

• CORTEX STEROID HORMONES SECRETED
• MEDULLA CATECHOLAMINES

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CORTEX STEROID HORMONES SECRETED

• MINERALOCORTICOIDS
• GLUCOCORTICOIDS
• SEX HOMONES

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MINERALOCORTICOIDS

• ALDOSTERONE
• ELECTROLYTE BALANCE
• BLOOD PRESSURE
• RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM

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GLUCOCORTICOIDS

• CORTISOL
• GLOCONEOGENESIS
• PERMISSIVE ACTIONS
• STRESS ADAPTATION
• ANTI-INFLAMITORY AND IMMUNOSUPPRESSANT

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REGULATION OF CORTISOL SECRETION
DIURNAL RHYTHM
HYPOTHALAMUS
STRESS

-

CRH
ANTERIOR PITUITARY
INCREASED BLOOD GLUCOSE BLOOD AA BLOOD FATTY ACIDS
-
ACTH
ADRENAL CORTEX
CORTISOL
TARGET ORGANS
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SEX HOMONES

• ANDROGENS (TESTOSTERONE)
• ESTROGENS
• LESS THAN GONADS

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ADRENAL OVERSECRETION

• MINERALCORTICOIDS SODIUM RETENTION, POTASSIUM
  DEPLETION
• CORTISOLEXCESS GLUCONEOGENESIS-EXCESS GLUCOSE
  DEPOSITED AS FAT
• ANDROGENMASCULINIZATION, PSEUDOHERMAPHODITISM,
  PRECOCIOUS PSEUDOPUBERTY, NO EFFECT IN ADULT
  MALES

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ADRENAL INSUFFICIENY

• CORTEX ADDISONS DISEASE
• POOR RESPONSE TO STRESS
• LACK OF PERMISSIVE ACTION
• POTASSIUM RETENTION
• HYPOTENSION

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MEDULLA CATECHOLAMINES

• A MODIFIED SYMPATHETIC POST GANGLIONIC NEURON
• EPINEPHRINE

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ACTIONS OF EPINEPHRINE

• MIMICS SYMPATHETIC NS
• MOBILIZES STORED FAT AND CARBOHYDRATE
• HEART AND BLOOD VESSELS

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GENERAL ADAPTATION SYNDROME

• FLIGHT OR FIGHT
• EPINEPHRINE
• CRH-ACTH-CORTISOL
• RENIN-ANGIOTENSIN-ALDOSTERONE
• VASOPRESSIN
• COORDINATED BY HYPOTHALAMUS
• CAN BE INDUCED PSYCHOSOCIALLY

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CONTROL OF FUEL METABOLISM

• GLYCOGENESIS
• GLYCOGENOLYSIS
• GLUCONEOGENESIS
• PROTEIN SYNTHESIS
• PROTEIN DEGRADATION
• FAT SYNTHESIS
• FAT BREAKDOWN

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ANABOLISM VS CATABOLISM

• BUILD UP VS BREAKDOWN OF LARGE MOLECULES
• ANABOLISM REQUIRES ENERGY (ATP)
• CATABOLISMENERGY PRODUCTION

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PANCREATIC HORMONES

• INSULIN
• GLUCAGON

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INSULIN ACTION ON BLOOD SUGAR

• BETA CELLS IN ISLETS OF LANGERHANS INSULIN
• FACILITIES GLUCOSE ENTRY INTO CELLS
• STIMULATES GLYCOGENESIS
• INHIBITS GLYCOGENOLYSIS
• INHIBITS GLUCONEOGENESIS

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INSULIN ACTION ON FAT

• INCREASES TRANSPORT INTO ADIPOSE CELLS
• PROMTES TRIGLYCERIDE SYNTHESIS
• INHIBITS LIPOLYSIS

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INSULIN ACTION ON PROTEIN

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

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CONTROL OF INSULIN SECRETION

• NEGATIVE FEEDBACK BLOOD SUGAR
• BLOOD AA
• GI HORMONES
• PARASYMPATHETIC ACTIVITY

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TWO TYPES OF DIABETES MELLITUS

• TYPE I AUTOIMMUNE DESTRUCTION OF BETA CELLS,
  LACK OF INSULIN SECRETION
• TYPE II REDUCED SENSITIVITY OF INSULIN RECEPTORS

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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

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GLUCAGON

• PANCREATIC ALPHA CELLS
• GENERALLY OPPOSES ACTIONS OF INSULIN
• DECREASE GLYCOGEN SYNTHESIS
• PROMOTE GLYCOGENOLYSIS
• STIMULATE GLUCONEOGENESIS
• PROMOTES FAT BREAKDOWN
• ONLY IN LIVER PROTEIN CATABOLISM

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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

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CONTROL OF CALCIUM METABOLISM

• PARATHYROID HORMONE
• CALCITONIN
• VITAMIN D

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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)

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CALCITONIN

• C CELLS OF THYROID GLAND
• DECREASE IN CA MOBILIZATION FROM BONE
• NOT AS IMPORTANT AS PTH AND VITAMIN D

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VITAMIN D

• ACTUALLY A HORMONE
• RELEASED FROM SKIN BY SUNLIGHT
• TWO STEP ACTIVATION LIVER AND KIDNEYS
• INCREASES CALCIUM ABSORPTION IN INTESTINE

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PTH HYPOSECRETION

• LOW CALCIUM AND HIGH PHOSPHATE
• MUSCLE SPASMS
• MENTAL CHANGES

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VITAMIN D DEFICIENCY

• IMPARED ABSORPTION OF CALCIUM
• PTH MAINTAINS PLASMA LEVEL AT EXPENSE OF BONES
• RICKETS IN CHILDREN
• OSTEOMALACIA IN ADULTS