THE ENDOCRINE SYSTEM

D. C. MIKULECKYPROFESSOR OF PHYSIOLOGY

ANDFACULTY MENTORING PROGRAM

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

WHAT IS A SIGNAL?

• SEMIOTICS

• INFORMATION THEORY

• NERVOUS SYTEM

• ENDOCRINE

• PARACRINE

• ENDOCRINE

• ANTIBODIES AND OTHER FOREIGN SUBSTANCES

• PARALLEL PROCESSING

CHEMICAL SIGNALS

• SIGNALING MOLECULE IS SECRETED

• TRAVELS FRON ONE SITE TO ANOTHER

• RECEPTOR AT TARGET

• BINDING TO RECEPTOR EFFECTS SOME CHANGE

ELEMENTS OF CELL SIGNALLING MECHANISMS

• SIGNAL MOLECULES

• RECEPTORS

• SIGNAL TRANSDUCTION

SIGNAL MOLECULES (FIRST MESSENGERS)

• NEUROTRANSMITTERS

• HORMONES

• LOCAL MEDIATORS

EXAMPLES OF SIGNALLING MOLECULES

TYPE OF MOLECULE LOCAL MEDIATOR NEUROTRANSMITTER HORMONE

PEPTIDES --- NEUROPEPTIDES VASOPRESSIN

POLYPEPTIDES --- --- INSULIN

AMINO ACIDS ANDDERIVATIVES

HISTAMINE GLYCINE EPINEPHRINE

FATTY ACIDDERIVATIVES

PROSTAGLANDINS --- TESTOSTERONE

OTHER SMALLMOLECULES

--- ACETYLCHOLINE ---

(SEE TABLE 1 IN TEXT)

RECEPTORS

• CELL MEMBRANE: HYDROPHILIC SIGNAL MOLECULES (POLYPEPTIDES, CATECHOLAMINES)

• CYTOPLASMIC: HYDROPHOBIC SIGNAL MOLECULES (STEROIDS, VITAMIN D, THYROID HORMONE*)

*BOUND TO CARRIER PROTEIN

LIGANDS, AGONISTS AND ANTAGONISTS

• LIGANDS BIND TO RECEPTORS IN A SPECIFIC MANNER

• LIGANDS THAT ELICIT A PHYSIOLOGICAL RESPONSE ARE AGONISTS

• LIGANDS THAT OCCUPY THE RECEPTOR BUT ELICIT NO RESPONSE ARE ANTAGONISTS (OR “BLOCKERS”)

EXAMPLES OF ANTAGONISTS

• PROPRANOLOL BLOCKS THE EFFECTS OF CATECHOLAMINES BY BINDING TO THEIR RECEPTORS

• SPIRONOLACTONE BLOCKS ALDOSTERONE (DIURETIC)

REGULATION OF RECEPTOR QUANTITY AS A CONTROL MECHANISM

• DESENSITIZATION BY DOWNREGULATION DUE TO INCREASED ANTAGONIST LEVELS

• INTERNALIZATION OF COMPLEX BY ENDOCYTOSIS

• RECEPTOR SYNTHESIS (UPREGULATION)

AN EXAMPLE OF RECEPTOR RECYCLING

MEMBRANE RECEPTORSG-PROTEIN RECEPTOR SUPERFAMILY

• MORE THAN 250 MEMBERS

• SERPENTINE GLYCOPROTEINS LOOP BACK AND FORTH THROUGH MEMBRANE

• EXTRACELLULAR DOMAIN: AMINO TERMINAL PEPTIDE AND THREE LOOPS (HYDROPHILIC REGIONS)

• IN THE MEMBRANE:SEVEN ALPHA HELICES OF ABOUT 25 HYDROPHOBIC AA

• SEE FIG 8 IN TEXT

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

HYPOTHALAMUS

NEUROSECRETORYNEURONS

ANTERIOR PITUITARY

POSTERIORPITUITARY

SYSTEMICARTERY

SYSTEMICVEIN

VASOPRESSIN

OXYTOCIN

HYPOTHALAMUS AND ANTERIOR PITUITARY

HYPOTHALAMUS

NEUROSECRETORYNEURONS

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

POSTERIORPITUITARY