Download Hormones (Types and Characteristics)

HORMONES
‛Ormh (hormae), an impetus or
stimulus
OUTLINE
•
•
•
•
•
•
•
•
OVERVIEW (NOT QUITE THE BIG PICTURE)
CLASSIFICATIONS & CHEMICAL TYPES
CHARACTERISTICS
SYNTHESIS/ DESTRUCTION (RATES)
ASSAYS
GENERAL MECHANISMS
THE ENDOCRINE SYSTEM
MISCELLANEOUS DETAILS (JUST WHAT
YOU WERE WAITING FOR)
• SUMMARY (THE END AT LAST)
HORMONES
ARE ESSENTIALLY MESSENGER
MOLECULES THAT ARE MEANT TO COORDINATE
THE OPERATIONS OF BIOLOGICAL ORGANISMS.
THIS IS DONE BY INCREASING AND DECREASING
THE FUNCTIONS OF CELLS. AN EXAMPLE OF TWO
RELATED HORMONES ARE:
THESE HORMONES
ARE SECRETED BY
THE THYROID GLAND.
THEY AFFECT GENERAL
METABOLIC RATES 
THE FIRST HORMONE TO BE DISCOVERED “WAS ANTIDIABETIC FACTOR” IN 1921 BY BANTING, BEST AND
THEN COLLIP (in MacLeod’s lab in Toronto, Canada).
TO SHOW YOU HOW DISCOVERIES ARE GENERATED,
THE DIABETIC FACTOR IDEA CAME FROM OSKAR
MINKOWSKI AND JOSEF von MERING IN 1889 WHEN THEY
PRODUCED A DIABETIC DOG BY REMOVING ITS PANCREAS
BUT ACTUALLY THEY WERE STUDYING FAT DIGESTION!
TYPES (CLASSIFICATIONS) OF
HORMONES
EXTERNAL CELL HORMONES: ENDOCRINE, PARACRINE, AND
AUTOCRINE
ENDOCRINE HORMONES ARE MADE AND SECRETED BY
ENDOCRINE GLANDS (HYPOTHALMIC/PITUITARY SYSTEM
AND SEMI-INDEPENDENT SYSTEMS). THEY TRAVEL
THROUGH THE BLOOD STREAM TO TARGET TISSUES (CELLS).
THESE WERE THE ORIGINAL HORMONES TO BE STUDIED.
PARACRINE HORMONES ARE MADE BY A LOCAL GROUP OF
CELLS IN A SPECIFIED TISSUE. THE HORMONES ARE
SECRETED INTO THE INTERSTITIAL FLUID SURROUNDING
THE CELLS.
CHOLECYSTOKININ-8 (GI TRACT HORMONE)
NH3-Asp-Tyr-Met-Gly-Trp-Met-Asp-Phe-CONH2
AUTOCRINE HORMONES ARE HORMONES MADE BY THE
CELLS THAT USE THEM; SELF-MODULATING HORMONES.
ESTRADIOL (SUPPORTS WOMB CELLS)
INTERNAL CELL HORMONES THESE ARE HORMONES
THAT ARE MADE AND FUNCTION ENTIRELY WITHIN THE
CONFINES OF A CELL. THEY ARE ALSO CALLED 2ND
MESSENGERS. THEY ARE TO BE DISTINGUISHED
FROM SOME EXTERNAL HORMONES (SUCH AS STEROIDS)
THAT ENTER A CELL FROM THE OUTSIDE.
cAMP TRANSFERS THE SIGNAL FROM A
CELL SURFACE RECEPTOR TO A SERIES OF
MOLECULES (OFTEN ENZYMES) THAT WILL
AMPLIFY THE ORIGINAL SIGNAL MANY FOLD
OVER. THIS IS CALLED A CASCADE MECHANISM.
cGMP PRODUCES OPPOSING EFFECTS. CALCIUM AND
CALMODULIN WORK AS A PAIR IN ANOTHER INTERNAL
SYSTEM. NITRIC OXIDE (THE GAS) IS STILL ANOTHER
INTERNAL CELL HORMONE.
HORMONE CHARACTERISTICS
● SIZE (MOLECULAR WEIGHT) TYPICALLY SMALL
MOLECULES (EXCEPTIONS INCLUDE POLYPEPTIDE
HORMONES SUCH AS GROWTH HORMONE).
OXYTOCIN IS A CYCLIC PEPTIDE WITH A MOLECULAR WEIGHT
OF 1007. IT IS MADE IN THE POSTERIOR PITUITARY GLAND
AND STIMULATES UTERINE CONTRACTION AT BIRTH.
DURATION OF EXISTENCE HORMONES GENERALLY
HAVE SHORT ½ LIVES* THAT CAN BE MEASURED BY THE
AMOUNT OF ACTIVE HORMONE THAT SURVIVES
AFTER A GIVEN TIME OR NUMBER OF PASSAGES
THROUGH THE CIRCULATION. THIS CONCEPT IS SOMEWHAT DECEIVING SINCE THERE ARE OTHER FACTORS
THAT CONTRIBUTE TO HORMONE AVAILABILITY
TO CAUSE A CELLULAR RESPONSE:
1. BIOAVAILABILITY – IS THE HORMONE FREE OR BOUND?
2. RATE OF SYNTHESIS – IS IT MAXIMAL, MINIMAL?
3. RATE OF DEGRADATION – TISSUE CONTRIBUTION?
* ½ LIFE = THE AMOUNT OF TIME THAT A SUBSTANCE EXISTS UNTIL IT
IS REDUCED BY 1/2. THE REDUCTION OF HORMONE (ACTIVITY)
OFTEN FOLLOWS EXPONENTIAL DECAY N(t) = No x 2-t/t1/2
AFTER 3 HALF-LIVES ONLY 1/8 OF AN ACTIVE HORMONE SURVIVES.
MORE INFORMATION ABOUT ½ LIVES:
CONSIDER THE HORMONE T4 (THYROXINE) AS AN EXAMPLE – IT
HAS A ½ LIFE OF 7 DAYS WITH A NORMAL BLOOD LEVEL OF 7.5 mg
PER 100 mL OF BLOOD.
AFTER 21 DAYS (THREE - ½ LIVES), THE AMOUNT WOULD BE
REDUCED TO ~0.94 mg PER 100 Ml OF BLOOD EXCEPT THAT THE
SUPPLY IS CONSTANTLY BEING RENEWED BY THE THYROID
GLAND.
SOME TYPICAL ½ LIVES OF HORMONES:
THYROID RELEASING HORMONE……………..2 MIN
INSULIN……………………………………………..6 MIN
GLUCAGON………………………………………. 7 MIN
GROWTH HORMONE……………………………25 MIN
CORTISOL…………………………………………90 MIN
THE VALUE OF KNOWING ½ LIVES – EVEN THOUGH CELLULAR
METABOLISM RENEWS MANY HORMONES QUICKLY - IS AS AN
INDICATOR OF HOW TIGHTLY THEIR LEVELS AND EFFECTS ARE
CONTROLLED. THE SHORTER THE ½ LIFE, THE TIGHTER THE
CONTROL.
OVERALL IT CAN BE REASONABLY STATED THAT
MOST HORMONES, ONCE SYNTHESIZED, ONLY
REMAIN FOR MINUTES BEFORE INACTIVATION
AND/OR REMOVAL BY TISSUES SUCH AS LIVER,
KIDNEYS & LUNGS. THE REASON -- IS TO RETAIN
TIGHT CONTROL OVER BODILY/ CELLULAR
FUNCTIONS IS ONE OF NECESSITY ESPECIALLY
WITH FUNCTIONS SUCH AS BLOOD SUGAR LEVELS
AND UPTAKE. THEREFORE, BOTH SYNTHESIS AND
RELEASE OF HORMONES ARE EQUALLY IMPORTANT.
ENDOCRINE HORMONES ARE RELEASED IN THE
BLOOD RAPIDLY ONCE SIGNALLED.
AS PART OF THE SYSTEM OF CHECKS & BALANCES SOME HORMONES HAVE COUNTERPARTS THAT
PRODUCE OPPOSING EFFECTS: INSULIN PROMOTES
GLUCOSE UPTAKE INTO CELLS WHILE GLUCAGON
PROMOTES GLUCOSE RELEASE FROM LIVER.
EXAMPLE OF VARYING LEVELS OF HORMONES DURING
THE MENSTRUAL CYCLE
HOW FAST CAN HORMONES CAUSE EFFECTS?
THIS TEST DESIGNED TO TEST INSULIN LEVELS & FUNCTION. NOTE THE NORMAL (GOLD)
CURVE. GLUCOSE LEVEL RETURNS TO NORMAL VALUE IN 3 HRS. THEN NOTE THE DIABETIC
CURVE (RED). AFTER 5 HRS GLUCOSE REMAINS WELL ABOVE NORMAL -- INSUFFICIENT
INSULIN TO CAUSE CELL UPTAKE OF GLUCOSE. HYPOGLYCEMIA (PURPLE) HAS MANY
CAUSES, ONE BEING A TUMOR CAUSING EXCESSIVE INSULIN OUTPUT. FASTING IS
ANOTHER.
THE PRINCIPLE OF RADIOIMMUNOASSAYS
THESE ASSAYS WORK SO WELL SINCE THEY COMBINE
RADIOACTIVE LABELLING WITH ANTIGEN-ANTIBODY
REACTIONS:
1)
2)
3)
RADIOACTIVE AND NON-RADIOACTIVE COMPOUNDS OF THE SAME
CHEMICAL COMPETE FOR REACTION WITH AN ANTIBODY (COMPLEX).
THE COMPLEX IS ISOLATED & MEASURED FOR RADIOACTIVTY.
THE SAMPLE IS NON-RADIOACTIVE WHILE A REFERENCE CHEMICAL
IS RADIOACTIVE.
VERY LOW
SAMPLE
VERY HIGH
RADIOACTIVITY
LOW
SAMPLE
INTERMEDIATE
SAMPLE
HIGH
SAMPLE
VERY HIGH
SAMPLE
HIGH
RADIOACTIVITY
INTERMEDIATE
RADIOACTIVITY
LOW
RADIOACTIVTY
VERY LOW
RADIOACTIVTY
HOW ARE HORMONES ASSAYED?
HORMONE BLOOD LEVELS ARE QUITE SMALL:
1x10-6 to 1x10-15 M
IN THE ASSAY, NON RADIOACTIVE
HORMONE (FROM THE PATIENT)
COMPETES WITH A STANDARD
AMOUNT OF RADIOACTIVE
HORMONE FOR BINDING TO AN
ANTIBODY. THE AMOUNT OF
NON-RADIOACTIVE HORMONE
(BOUND TO THE ANTIBODY) IS
READ FROM A STANDARD CURVE
THAT IS SHOWN TO THE RIGHT
(SEE ARROW).
CHEMICAL CLASSES OF HORMONES
(EXAMPLES)
AMINO ACID DERIVED: THYROXINE
PEPTIDE HORMONES: GROWTH HORMONE &
OXYTOCIN
Growth hormone:
22, 124 daltons
LIPID DERIVED:
1) CHOLESTEROL
DERIVED --
2) FATTY ACID DERIVED –
PROSTAGLANDIN F2a
THE STEROIDS ARE DERIVED
FROM CHOLESTEROL WHERE
CORTISOL IS ANTI-INFLAMMATORY
AND ESTRADIOL SUPPORTS
UTERINE FUNCTIONS. PGF2a CAUSES
THE CONTRACTION OF SMOOTH
MUSCLES.
GENERAL HORMONE MECHANISMS:
(ENDOCRINE TYPES)
1. AT THE CELL SURFACE
(to a receptor protein)
2. AT THE CELL NUCLEUS
(through a receptor protein)
1
2
THE ENDOCRINE HORMONE SYSTEM
HORMONES OF THE ENDOCRINE (endokrinein - to
separate inside) SYSTEM ARE SECRETED (RELEASED)
DIRECTLY INTO THE BLOOD STREAM. THAT IS TO BE
DISTINGUISHED FROM EXOCRINE GLANDS THAT SECRETE
MOLECULAR PRODUCTS INTO A DUCT. e. g. A SWEAT GLAND.
THESE HORMONES ARE MADE IN A PECKING ORDER –
STARTING FROM THE BRAIN’S HYPOTHALAMUS. BUT,
YOU MAY HAVE GUESSED, THERE ARE INDEPENDENT
OPERATORS SUCH AS THE PANCREAS. GENERAL OBJECTIVE:
TO COORDINATE BODILY FUNCTIONS.
MAJOR ENDOCRINE
ORGANS/ GLANDS
THE PANCREAS IS
AUTONOMOUS FROM
THE BRAIN AS WELL
AS ADIPOSE TISSUE
(THAT MAY BE A SURPRISE).
THE ENDOCRINE “PECKING ORDER”
NEURAL
PAIN, FEAR,
INFECTION,
HEMORRHAGE,
HUNGER
THE INITIATION OF HORMONAL
ACTION MAY BEGIN WITH
AFFERENT NERVE SIGNALS TO THE HYPOTHALAMUS.
THIS CAUSES THE DUMPING OF RELEASING FACTORS
INTO THE PORTAL ARTERIAL SYSTEM THAT, IN TURN,
GO TO THE ANTERIOR PITUITARY. IN SOME CASES
NERVE SIGNALS GO TO THE POSTERIOR PITUITARY.
BOTH PITUITARY SECTIONS RELEASE THEIR
OWN HORMONES.
RELEASING FACTORS (WHICH ARE HORMONES)
MIGRATE TO A PRIMARY TARGET (THE ANTERIOR
PITUITARY) WHICH RELEASES ITS OWN
HORMONE (HORMONE B). B TRAVELS IN THE
CIRCULATORY SYSTEM TO A SECONDARY
TARGET TISSUE. THIS CAUSES THE RELEASE
OF HORMONE C. HORMONE C, IN TURN, TRAVELS
TO ITS ULTIMATE TARGET TISSUE, BINDS TO IT,
AND BRINGS ABOUT A PHYSIOLOGICAL EFFECT(S).
REMEMBER THAT EACH STAGE OF BINDING AND
RELEASE AMPLIFIES THE ORIGINAL SIGNAL
MANY FOLD.
THE ENDOCRINE “PECKING ORDER”
NEURAL
WE CAN FOLLOW A TYPICAL SEQUENCE OF
EVENTS TO SIGNAL AN INCREASE IN METABOLIC
RATE:
1) A CONFLICT PRESENTS ITSELF TO THE CNS – e. g.
A TASK MUST BE COMPLETED IN A WEEK.
2) THE CNS SIGNALS THIS TO THE HYPOTHALAMUS
CAUSING THE RELEASE OF THYROTROPINRELEASING HORMONE (TRH).
3) THIS HORMONE TRAVELS TO THE ANTERIOR PITUITARY GLAND (via portal vein) CAUSING THE RELEASE
OF THYROID STIMULATING HORMONE (TSH).
4) TSH, IN TURN, IS CARRIED TO THE THYROID GLAND
(via the blood) WHERE IT CAUSES THE RELEASE OF
THYROXINE AND TRIIODOTHYRINE (T4 AND T3).
5) T4 AND T3 BIND TO MOST CELLS IN THE NUCLEUS AND
STIMULATE AN INCREASE IN METABOLIC RATE.
ALTHOUGH THIS MAY BE AN OVERSIMPLIFICATION – SINCE
HORMONES AND THEIR OPERATION ARES COMPLICATED –
STILL WE CAN CONSIDER SOME PRACTICAL EXAMPLES.
THESE ARE EASILY SEEN IN COUPLES OR EVEN SMALL GROUPS –
1) ONE LIKES TO HAVE THE THERMOSTAT SET AT 72 deg WHILE
THE OTHER WANTS IT AT 66 deg.
2) ONE LIKES TO HAVE HIS/HER WORK DONE IMMEDIATELY
WHILE THE OTHER PREFERS A LITTLE MORE TIME.
3) ONE CAN WALK THROUGH THE WOODS AND LEAVE THE
OTHER BEHIND IN A FEW MINUTES.
THESE ARE EXAMPLES OF SMALL DIFFERENCES IN METABOLIC
SET POINTS OF THE THYROID GLAND AND ITS HORMONE OUTPUTS
– SOME PEOPLE WOULD DEFINE THEM AS TYPE A AND TYPE B
PERSONALITIES.
SOME THINGS NOT PREVIOUSLY EXPLAINED:
1. MANY HORMONES HAVE FEEDBACK
AND SHUTDOWN MECHANISMS
(e. g., thyroid hormones affect TSH release by TRH)
2. THERE MAY BE A LAG BEFORE AN EFFECT
CAN OCCUR (AND THE REVERSE).
(e. g., growth hormone’s effects are especially slow)
3. HORMONE EXCESSES AND DIMINUTIONS
MAY BE PATHOLOGICAL.
(e. g., excess cortisol levels may cause kidney stones)
4. SPECIFIC HORMONE ACTIONS ARE
DETERMINED BY THE KIND OF
RECEPTORS THAT THEY BIND TO.
5. SOME HORMONES MAY FUNCTION AS
EITHER HORMONES OR NEUROTRANSMITTERS (LOCATION, LOCATION,
LOCATION), e. g., epinephrine and norepinephrine.
SUMMARY
1. HORMONES ARE CHEMICAL MESSENGERS
MEANT TO COORDINATE THE PHYSIOLOGICAL
SURVIVAL & FUNCTIONS OF AN ORGANISM.
2. TO SAY THAT HORMONES BELONG TO A
CHEMICAL CLASS WOULD BE ERRONEOUS –
THEY INCLUDE: PEPTIDES, POLYPEPTIDES,
AMINO ACID DERIVITIVES, STEROIDS,
FATTY ACID DERIVITIVES, CNUCLEOTIDES
AND OTHER TYPES.
3. THE CONCENTRATIONS OF HORMONES
ARE VERY SMALL, BUT THEIR SIGNALS
ARE AMPLIFIED GREATLY. THEY CAN BE
ASSAYED BY RIA.
4. THE ENDOCRINE SYSTEM WAS THE 1ST TO
BE STUDIED. IT ORIGINATES (FOR THE
MOST PART) IN THE HYPOTHALAMIC AND
PITUITARY TISSUES FROM CNS SIGNALS.
5. IN THE ENDOCRINE SYSTEM, HORMONES
BIND AT EITHER A CELL MEMBRANE
RECEPTOR OR AT THE NUCLEUS (via
an intracellular cell protein receptor)