RECALL THAT EXOCRINE GLANDS SECRETE INTO A DUCT
ENDOCRINE GLANDS SECRETE INTO THE BLOOD -
SECRETES HORMONE - WHICH ENTERS BLOOD -
CIRCULATES -
AND ACTS AT TARGET ORGAN BECAUSE IT HAS RECEPTORS FOR THE HORMONE
FUNCTION OF ENDOCRINE SYSTEM IS INTEGRATION AND CONTROL
OTHER SYSTEM THAT ALSO DOES THIS = NERVOUS SYSTEM -
ENDOCRINE CONTROL TENDS TO BE SLOWER AND LONGER-ACTING
BUT - TWO SYSTEMS VERY RELATED BECAUSE NEURONS ARE SECRETORY TOO
HAVE ALREADY SEEN A NUMBER OF EXAMPLES OF ENDOCRINE CELLS / ORGANS
RECALL ENTEROENDOCRINE CELLS, OVARY, TESTIS ETC.
LOOK NOW AT ENDOCRINE GLANDS PER SE - BUT IT'S REALLY A MIXED BAG
ISLETS OF LANGERHANS IN PANCREAS
HYPOPHYSIS - (PITUITARY) - CONTROLS MANY OTHER ENDOCRINE GLANDS
THYROID
PARATHYROIDS
ADRENAL
PINEAL - BUT UNCLEAR IF IT'S REALLY AN ENDOCRINE GLAND
ALL VERY DIFFERENT HISTOLOGICALLY -
ONE COMMON FEATURE IS GOOD VASCULAR BED
CHEMICAL NATURE OF HORMONES:
SOME SMALL PEPTIDES, SOME LARGER PROTEINS AND GLYCOPROTEINS
OTHERS ARE STEROIDS
FEATURES OF SECRETORY CELLS:
PROTEIN SECRETING CELLS LOOK TYPICAL (RER, GOLGI, GRANULES)
BUT MUCH LESS SO THAN PANCREAS, ETC.
TYPICALLY HAVE RELATIVELY FEW GRANULES NEAR BLOOD VESSELS
HORMONES ACTIVE AT LOW CONCENTRATIONS
STEROID SECRETING CELLS HAVE LOTS OF SER, VERY LITTLE RER, LARGE GOLGI
LIPID DROPLETS IN CYTOPLASM = PRECURSORS OF HORMONES (CHOLESTEROL)
MITOCHONDRIA TYPICALLY HAVE VESICULAR CRISTAE
MECHANISM OF ACTION OF HORMONES INTERESTING:
ALL CIRCULATE IN ENTIRE BODY
ONLY ACT AT TARGET ORGANS BECAUSE TARGET HAS RECEPTORS
THE HORMONE BINDS SPECIFICALLY TO THE RECEPTOR - BASED ON SHAPE
WHAT PRECISELY HAPPENS DEPENDS ON TYPE OF HORMONE
PROTEIN HORMONE - BINDS TO RECEPTOR IN MEMBRANE
THIS ACTIVATES ENZYME INSIDE OF MEMBRANE -
CLASSIC EXAMPLE = ADENYLATE CYCLASE -
CATALYZES CONVERSION OF ATP TO cAMP
cAMP = SECOND MESSENGER -
THIS ACTIVATES OTHER ENZYMES - COLLECTIVELY CALLED KINASES
THESE ACTIVATE SPECIFIC ENZYMES WHICH CAUSE RESPONSE TO HORMONE
WORKS LIKE A CASCADE - CALLED THE SECOND MESSENGER CONCEPT
(HORMONE = 1ST MESSENGER, cAMP = 2ND MESSENGER)
STEROID HORMONES ARE LIPID BASED -
CAN GO THROUGH MEMBRANE - THEY DO
THEN BIND TO INTRACELLULAR RECEPTOR -
RECEPTOR / HORMONE COMPLEX GOES TO NUCLEUS - CAUSES CHANGE THERE
CAUSES INCREASE IN SYNTHESIS OF THE ENZYMES THAT DO EFFECT
SO! SUMMARY = PROTEINS ACTIVATE ENZYMES - STEROIDS MAKE NEW ONES
OF COURSE EVERYTHING WORKS BY ENZYMES - AND RECOGNITION ALWAYS BY SHAPE
STEROID HORMONES TEND TO HAVE LONGER LASTING EFFECTS
ISLETS OF LANGERHANS
RECALL MOST OF THE PANCREAS = EXOCRINE
SCATTERED WITHIN THIS ARE THE ISLETS - SEPARATED BY RETICULAR C.T.
THE ISLET ITSELF = CELLS ARRANGED IN IRREGULAR CORDS AND CLUMPS
SUPPORTED BY RETICULAR C.T. AND SURROUNDED BY MANY BLOOD VESSELS
THE CAPILLARIES HERE ARE FENESTRATED
THIS IS VERY TYPICAL OF ENDOCRINE ORGANS -
CORDS AND CLUMPS OF CELLS - FENESTRATED CAPILLARIES.
TYPICAL STAINS - ISLETS PALER THAN SURROUNDING TISSUE -
BUT CANNOT SEE DIFFERENT CELL TYPES
SPECIAL STAINS CAN DISTINGUISH SEVERAL CELL TYPES
1. ALPHA CELLS - ABOUT 20% - RELATIVELY LARGE GRANULES STAIN RED WITH MOST DYES
2. BETA CELLS - ABOUT 75% - SMALLER GRANULES WHICH STAIN BLUE
3. DELTA CELLS -
4. SEVERAL MORE - MOSTLY SPECIES-SPECIFIC C THROUGH G
OFTEN NOW NAMED VIA HORMONE PRODUCED
EM- ALL ARE TYPICAL PROTEIN-SECRETING ENDOCRINE CELLS -
BUT RELATIVELY MANY GRANULES
GRANULES DIFFER SOMEWHAT, BUT WE'LL NOT WORRY ABOUT THAT
FUNCTIONAL CONSIDERATIONS
BETA CELLS MAKE INSULIN
POLYPEPTIDE HORMONE - REQUIRED FOR GLUCOSE UPTAKE BY SOME TISSUES
INSULIN DEPENDENT TISSUES = MUSCLE, LIVER, ADIPOSE TISSUE - WHERE MOST GOES
LACK OF INSULIN = DIABETES MELLITUS (NOT INSIPIDUS)
SHOULD NOTE THAT THIS = JUVENILE ONSET (OR INSULIN DEPENDENT) DIABETES
CONSEQUENCES - HIGH BLOOD GLUCOSE - MUSCLE WASTING- KETOSIS - KIDNEY FAILURE
TREATMENT = INJECT INSULIN - NOW ALL RECOMBINANT "HUMULIN"
ALPHA CELLS PRODUCE GLUCAGON - HAS OPPOSITE EFFECT - RAISES BLOOD SUGAR
INTERACT THROUGH FEEDBACK LOOPS TO CONTROL BLOOD GLUCOSE
DELTA CELLS SECRETE SOMATOSTATIN - INHIBITS THE OTHER TWO
HYPOPHYSIS - PITUITARY
VERY IMPORTANT - CONTROLS MANY OTHER ENDOCRINE GLANDS
GROSS ANATOMY - SIZE OF GRAPE -BELOW HYPOTHALAMUS -
CONNECTED TO HYPOTHALAMUS VIA STALK
SITS IN BONY SADDLE = SELLA TURCICA
2 MAJOR SUBDIVISIONS - REFLECT EMBRYONIC ORIGINS
1. NEUROHYPOPHYSIS - DEVELOPS AS DOWN GROWTH FROM BRAIN
2. ADENOHYPOPHYSIS - ORIGINATES AS UP GROWTH FROM ROOF OF PRIMITIVE PHARYNX
= RATHKE'S POUCH
EACH HAS SUBDIVISIONS
ADENO HAS THREE
PARS DISTALIS = ANTERIOR PITUITARY
PARS TUBERALIS
PARS INTERMEDIA
NEUROHYPOPHYSIS
INFUNDIBULUM = MEDIAN EMINENCE + INFUNDIBULAR STALK
INFUNDIBULAR PROCESS - USUALLY CALLED PARS NERVOSA
WHAT YOU MOSTLY DEAL WITH IS PARS DISTALIS AND PARS NERVOSA,
WITH A SMALL PARS INTERMEDIA
PARS DISTALIS
TYPICAL ENDOCRINE AS WE'VE DESCRIBED
CORDS AND CLUMPS OF CELLS, LOTS OF B.V. - HERE= THIN WALLED SINUSOIDS
SUPPORTED BY SOME C.T. - BUT NOT A LOT -
SURROUNDED BY COLLAGENOUS CAPSULE
THIS MAKES MANY HORMONES - ALL CONTROLLED BY HYPOTHALAMUS
CELLS OF DISTALIS HAVE BEEN CLASSIFIED DIFFERENT WAYS OVER THE YEARS
NOW WE USE IMMUNOHISTOCHEMISTRY TO LOCALIZE THE VARIOUS HORMONES
MORE CLASSIC WAY TO SEPARATE IS BY STAINING ACIDOPHILS VS. BASOPHILS -
CAN SEE DIFFERENCES IN STAINING BY LM
LOOK AT EACH CELL TYPE, WHAT HORMONE, TARGET, ACTION
ACIDOPHILS
1. SOMATOTROPE - PRODUCES GROWTH HORMONE OR SOMATOTROPIN
TARGET? - ENTIRE BODY ACTION? - INCREASE GROWTH, METABOLISM
ONE SPECIFIC TARGET = EPIPHYSEAL PLATES -
CAUSE GROWTH IN LENGTH OF LONG BONES (MAKES A PERSON TALLER)
DYSFUNCTION? - TOO MUCH = GIANT : TOO LITTLE = DWARF
IF TOO MUCH AFTER PLATES CLOSE = AGROMEGALY - ( REMEMBER ANDRE THE GIANT)
USED TO BE PROCURED FROM CADAVERS, NOW MADE BY RECOMBINANT DNA + MISUSED
2. MAMMOTROPE (LUTEOTROPE)
HORMONE = PROLACTIN - SO IN NON-LACTATING WOMAN CELLS NON-DESCRIPT
TARGET = MAMMARY GLAND
EFFECT = INCREASE PRODUCTION OF MILK
SOME ANIMALS HAS A STRONG LUTEOTROPIC EFFECT -
PROMOTES PROGESTERONE SECRETION FROM CORPUS LUTEUM
BASOPHILS
1. THYROTROPES
HORMONE = TSH - THYROID STIMULATING HORMONE
TARGET = THYROID; ACTION = SECRETION OF THYROID HORMONES
2. GONODOTROPES
HORMONE = FSH AND LH - WE'VE DISCUSSED
3. CORTICOTROPE
HORMONE = ACTH - ADRENOCORTICOTROPIC HORMONE
TARGET = ADRENAL CORTEX - ANOTHER ENDOCRINE GLAND
ACTION = STIMULATES PRODUCTION OF ADRENAL GLUCOCORTICOIDS - SEE LATER
CORTICOTROPE ALSO MAKES ENDORPHINS - WHICH ARE OPIATE-LIKE PAIN KILLERS
MAY ALSO FIND CELLS THAT DO NOT STAIN = CHROMOPHOBES - SIGNIFICANCE UNCLEAR
HYPOPHYSIS CONTROLLED BY HYPOTHALAMUS,
VIA RELEASING HORMONES - FROM HYPOTHALAMUS - SMALL POLYPEPTIDES
THESE ARE PRODUCED BY SECRETORY NEURONS IN HYPOTHALAMUS
AXONS GO LITTLE WAYS THEN SECRETE - R.H'S INTO CAPILLARIES
HYPOTHALAMUS DRAINED BY SMALL VEINS WHICH GO RIGHT TO PARS DISTALIS
= HYPOTHALAMO-HYPOPHYSEAL PORTAL SYSTEM (RECALL WHAT PORTAL SYSTEM=)
PARS INTERMEDIA
SOME ANIMALS HAVE LUMEN OF RATHKE'S POUCH LEFT - MAKES CLEFT
HUMANS JUST HAVE MAYBE A FEW EPITHELIAL-LINED CYSTS (SOMETIMES NOTHING)
IN GENERAL PARS INTERMEDIA SLIGHTLY DIFFERENT STAINING FROM P.DISTALIS
MOST SPECIES PRODUCE MSH HERE - NOT AS IMPORT IN HUMANS
MSH = MELANOCYTE STIMULATING HORMONE - A LOT LIKE ACTH - BOTH INCREASE IN PREGNANCY - ACTH WILL DARKEN SKIN TOO
NEUROHYPOPHYSIS
MOSTLY UNMYELINATED NERVE FIBERS - STAIN POORLY IN H+E
CELL BODIES ARE UP IN HYPOTHALAMUS - IN TWO NUCLEI (= GROUPS OF SOMA)
SUPRAOPTIC AND PARAVENTRICULAR
AXONS RUN DOWN INFUNDIBULAR STALK AND END BLINDLY NEAR CAPILLARIES IN PIT.
SO - HORMONES ARE MADE IN CELL BODIES (IN HYPOTHALAMUS)
BOUND TO A CARRIER PROTEIN (NEUROPHYSINS)
TRAVEL DOWN AXON AND ARE STORED IN DILATED TERMINALS OF AXONS
AXON TERMINATES JUST BELOW CAPILLARIES IN PARS NERVOSA - SECRETES INTO THEM
IF YOU USE SPECIAL STAIN SEE HERRING BODIES BY LM
EM - SEE THAT THESE ARE COLLECTIONS OF SECRETORY GRANULES
CELL BODIES IN PARS NERVOSA = PITUICYTES - LIKE GLIAL CELLS
HORMONES = OXYTOCIN AND ANTIDIURETIC HORMONE - WE'VE SEEN
THYROID GLAND
GROSS - ON VENTRAL SIDE OF LARYNX, AT JUNCTION WITH TRACHEA
2 LOBES CONNECTED BY ISTHMUS - SURROUNDED BY CAPSULE
UNIQUE FEATURE IS THAT IT STORES ITS HORMONE EXTRACELLULARLY AS INACTIVE COLLOID = THYROGLOBULIN
TAKES IT BACK AND SECRETES ACTIVE HORMONE INTO BLOOD = THYROID HORMONES
HISTOLOGY - MANY SPHERICAL, CYST-LIKE FOLLICLES - VARIABLE SIZES
CONTAIN COLLOID, LINED BY SIMPLE EPITHELIUM
HEIGHT OF EPITHELIUM VARIES - SQUAMOUS WHEN INACTIVE, COLUMNAR WHEN ACTIVE
FOLLICLES SURROUNDED BY BASAL LAMINA, SUPPORTED BY RETICULAR C.T.
LOTS OF CAPILLARIES BETWEEN FOLLICLES
LOOK CLOSELY AT FOLLICULAR CELLS - NUCLEUS SPHEROID,
CYTOPLASM MAY HAVE "CLEAR DROPLETS" - THOUGHT TO BE GLOBS OF COLLOID
EM - SEE VARIABLE RER AND QUITE A FEW LYSOSOMES + CLEAR DROPLETS
COLLOID - HOMOGENEOUS, USUALLY ACIDOPHILLIC (PINK) VERY PAS+
THYROGLOBULIN = GLYCOPROTEIN
THERE IS ANOTHER CELL TYPE BESIDES FOLLICULAR EPITHELIUM
FOUND BETWEEN FOLLICLES OR STUCK INTO THEM BETWEEN B.L. AND PRINCIPAL CELLS
= PARAFOLLICULAR OR "C" CELLS
LARGER THAN PRINCIPAL CELLS, STAIN LIGHTER EM-SEE SMALL GRANULES ETC.
THESE MAKE CALCITONIN - LOWERS BLOOD CALCIUM - RECALL FROM BONE LECTURES
WILL SEE THAT PARATHYROID RAISES BLOOD CALCIUM - IMPORT TO CONTROL IT
THYROID - FUNCTION - MAKES THYROID HORMONE AND STORES IT AS INACTIVE COLLOID - TAKES IT BACK UP AND SECRETES ACTIVE HORMONE
LIKE THIS:
1. SYNTHESIZE THYROGLOBULIN = LARGE GLYCOPROTEIN
2. IODINATE IT - SPECIFICALLY THE TYROSINE MOLECULES
3. RELEASE IT INTO COLLOID
4. REABSORB IT UNDER INFLUENCE OF TSH
5. HYDROLYZE THYROGLOBULIN TO T3 (TRIIODOTHYRONINE) AND THYROXINE
6. RELEASE IT INTO CAPILLARIES
SO! IODINE IS VERY IMPORTANT - THYROID CONCENTRATES IT
ACTION OF THYROID HORMONES - METABOLIC RATE OF ENTIRE BODY +
ROLE IN NORMAL DEVELOPMENT - ESPECIALLY LATE FETAL AND NEONATAL
PATHOLOGY -
HYPOTHYROIDISM IN INFANCY = CRETINISM =
STUNTED PHYSICAL AND MENTAL DEVELOPMENT
IN ADULT = MYXEDEMA - SLOW MINDED AND PUFFY, PITTING EDEMA
HYPERTHYROIDISM = VARYING DEGREES - WORST = GRAVE'S DISEASE
= EXOPTHALMOS, WEIGHT LOSS, NERVOUSNESS + HEAT INTOLERANCE
(THERAPY = RADIOIODINE)
GOITER = ENLARGED THYROID - DUE TO LACK OF IODINE - TRIES TO COMPENSATE
PARATHYROIDS
GROSS- IN HUMANS = 4 SMALL OVOID BODIES EMBEDDED IN THYROID
SEPARATED FROM THYROID BY C.T. SEPTA, ALSO SUBDIVIDE SOMEWHAT
PARENCHYMA = TYPICAL CORDS AND CLUMPS
TWO MAIN CELL TYPES IN HUMANS = CHIEF CELLS + OXYPHILIC CELLS
CHIEF = MOST OF THE CELLS ;
SMALLER, POLYGONAL, PALE, SOMEWHAT ACIDOPHILLIC CYTOPLASM
CAN ALSO SEE SMALL GRANULES AND GLYCOGEN IF YOU STAIN RIGHT
EM - AS ABOVE - SEE GLYCOGEN AND SMALL GRANULES
OXYPHILIC CELLS - OCCUR IN SMALL GROUPS, LARGER, STRONGLY ACIDOPHILLIC CYTOPLASM
EM- STRIKING FEATURE = MITOCHONDRIA, SOME GLYCOGEN BETWEEN THEM
FUNCTION PARATHYROID HORMONE = INCREASE BLOOD CALCIUM
INCREASE BONE REABSORPTION -
OSTEOCLASTS AND OSTEOCYTES SOMEWHAT
ALSO DECREASES CALCIUM CLEARANCE IN KIDNEY
ADRENAL GLAND
PAIRED - SIT AT TOP OF EACH KIDNEY
ACTUALLY TWO DISTINCT ENDOCRINE GLANDS - CORTEX AND MEDULLA
OUTSIDE FIND COLLAGENOUS CAPSULE - THEN CORTEX
CORTEX IN THREE ZONES
ZONA GLOMERULOSA - Z. FASCICULATA (BIGGEST) - Z. RETICULARIS
LIGHT MICROSCOPY:
ZONA GLOMERULOSA - CLOSELY PACKED ARCADES OF CELLS
SINGLE NUCLEI - SMALLER CELLS - CYTO ACIDOPHILLIC
RELATIVELY FEWER LIPID DROPLETS
Z. FASCICULATA - LONG PARALLEL CORDS OF LARGER CELLS
CAPILLARIES BETWEEN CORDS
MORE LIPID DROPLETS THAN Z.GLOM.
Z. RETICULARIS - JUST CORDS OF CELLS
SMALLER, FEWER LIPID DROPLETS AGAIN
USUALLY FIND LIPOFUSCIN GRANULES
ELECTRON MICROSCOPY - THESE ALL PRODUCE STEROID HORMONES
SO - SEE PLENTY OF SMOOTH E.R., LIPID DROPLETS
MITOCHONDRIA TEND TO HAVE TUBULAR OR VESICULAR CRISTAE
FUNCTION- CORTEX IS ESSENTIAL FOR LIFE
Z. GLOMERULOSA SECRETES HORMONES COLLECTIVELY CALLED MINERALOCORTICOIDS
PRINCIPAL ONE = ALDOSTERONE
THESE CONCERNED WITH FLUID AND ELECTROLYTE BALANCE
Z. FASC. + RETICULARIS SECRETE GLUCOCORTICOIDS - LIKE HYDROCORTISONE
WIDE RANGING EFFECTS - BASICALLY INCREASES UTILIZATION OF NUTRIENTS
POTENT ANTI-INFLAMMATORY
ALSO SECRETE SEX HORMONES, ESPECIALLY ANDROGENS
THESE RELEASED IN RESPONSE TO STRESS - PROTECTS BODY AGAINST IT SOMEWHAT
BUT, TOO MUCH STIMULATION (STRESS) DELETERIOUS
MEDULLA - JUNCTION BETWEEN CORTEX AND MEDULLA IRREGULAR
MEDULLARY CELLS (CHROMAFFIN CELLS) LARGE, SOMEWHAT PALE
FIND MANY BLOOD VESSELS - THAT DRAIN FROM CORTEX
IF YOU USE HISTOCHEMISTRY CAN IDENTIFY TWO CELL TYPES
ONE SECRETES EPINEPHRINE, THE OTHER NOREPINEPHRINE
EM- MOST STRIKING FEATURE IS GRANULES - DENSE CORE VESICLES =
CATECHOLAMINES - COLLECTIVE TERM FOR EPI AND NOR-EPI
FUNCTION - CATECHOLAMINES = FIGHT, FLIGHT, FRIGHT REACTION
GIVES SYSTEMIC SYMPATHETIC EFFECTS RAISES HEARTRATE, B.P. BREATHING ETC.
DRY MOUTH - INCREASED BLOOD SUGAR
PREGANGLIONIC SYMPATHETIC NERVE ENDINGS PLAY ROLE -
THEY TERMINATE IN THE MEDULLA AND CAUSE RAPID CATECHOLAMINE RELEASE
PINEAL
LIES IN ROOF OF OLD PART OF BRAIN (BRAINSTEM)
HISTOLOGY - TYPICAL APPEARANCE (CORDS AND CLUMPS ETC.)
CELLS CALLED PINEALOCYTES
IN HUMANS FIND CORPORA ARENACEA (BRAIN SAND) = CLUMPS OF MINERALIZED SUBSTANCE
FUNCTION - SEASONAL REPRODUCTIVE BEHAVIOR FOR ONE THING
SEEMS TO HAVE AN ANTI-GONADOTROPIC EFFECT -
IN SOME ANIMALS ACTUALLY SENSES LIGHT
IN HUMANS IT'S LARGER AND ACTIVE BEFORE PUBERTY, AFTERWARDS IT'S VERY SMALL
PINEAL ALSO MAY INFLUENCE CIRCADIAN RHYTHMS, PERHAPS VIA MELATONIN