Endocrine functions of the pancreas, pituitary and pineal glands 116

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Endocrine functions of the pancreas, pituitary
and pineal glands 1/16

• How do the two types of diabetes differ?
• Why do hormonal responses change?
• How does the hypothalmus regulate hormone
  release?
• What two hormones are created by the
  neurohypophysis?
• What six hormones are created by the
  adenohypophysis?
• How are hormones synthesized?
• What hormones are produced by the gonads?
• How does the pineal gland determine wakefulness?

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Practice Quiz for Monday and Wednesdaysnotes

• _______is a second messenger that increases
  intracellular calcium and is produced by the
  enzyme phospholipase-C.
• IP3 b) cyclicAMP c) Diacylglycerol d)
  Sodium
• Aldosterone is a steroid produced in what
  specific part of the adrenal gland?
• Medulla b) Cortex c) Zona glomerulosa d)
  Kidney
• Which receptor for epinephrine in causes fatty
  acids to be released from adipocytes as part of
  the Fight-or-Flight response?
• Alpha-1 b) Alpha-2 c) Beta-1 d) Beta-2 e)
  Beta-3
• Cholesterol is not a precursor to what adrenal
  hormone?
• a) Cortisol b) Aldosterone c) DHEA d)
  Epinephrine e) Insulin

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THE TWO TYPES OF DIABETES MELLITUS RESULT FROM
EITHER AN INABILITY TO SECRETE INSULIN OR THE
INABILITY OF SENSITIVE CELLS TO DETECT INSULIN.

• Type I, IDDM B-cells destroyed by autoimmune
  disease, reflux from bile duct, infection, or
  exocrine digestion
• Sensitive cells like heart, liver, adipocytes,
  muscle need insulin and insulin receptors to let
  glucose enter the cytosol!
• See tutorial http//arbl.cvmbs.colostate.edu/hboo
  ks/pathphys/endocrine/pancreas/index.html
• IDEA save glucose for the brain during fasting
  glucose dependent
• COST Without insulin, the glucose stays in
  blood?Hyperglycemia
• Why is Hyperglycemia a Problem?
• Hemes and proteins glycosylated loss of
  function!
• Blindness, Oxidative stress and Vasoconstriction
  due to glycosylation!
• Glucose is normally reabsorbed by the PCT of the
  nephron, if too much goes to the kidney it is not
  reabsorbed and it stays in the filtrate/urine
• Diabetes Insipidus? no ADH release from posterior
  pituitary! (no glucose in urine)

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IDDM (type-I) is usually juvenile in onset, and
requires insulin injections for life because beta
cells cant grow back!

• Dependent Cells Can Starve without insulin!gtgtSo
  they must metabolize fatty acids and ketones
  because these are less insulin dependent.
• Non-sugar metabolites cause metabolic acidosis!
• Fatty acid metabolism and excess blood glucose
  result in hepatic/heart/renal disease
• These individuals often BECOME obese because
  their brain thinks they are starving, when they
  just cant use the food thats there!
• Hyperinsulinemia overdose of replacement insulin
  causing hypoglycemia and neural tissue
  starvation. What would happen to your blood
  glucose if too much insulin was administered?
  Why do diabetics often carry a candy bar?

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Type II or Non-insulin Dependent Diabetes
Mellitus occurs when adipoctyes (mostly) stop
responding to insulin, often as a result of
energy excess.

• Same Symptoms polyuria, polydipsia, polyphagia.
• urine
  thirst eating
• why? why? why?
• Risk Factors Age, Heredity(family/cultural),
  Obesity
• Onset typically after age 40, now days it is
  often seen in obese college-age and younger
  persons.
• Adipocytes and other cells fail to respond to
  insulin and glucose influx after a meal becomes
  very slow, so glucose has nowhere to go.it
  accumulates in the blood causing hyperglycemia.
• Treat with exercise and better diet.

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Cellular responses to hormones/drugs can change.
WHY IS THIS IMPORTANT????

• Up Regulation exposure improves future
  sensitivity!
• Oxytocin and increasing numbers of receptors as
  birth approaches?More receptors? More contractile
  force!
• Down Regulation exposure decreases future
  sensitivity
• Insulin/Obesity reduced receptors causes Type II
  diabetes
• Fewer hormone receptors? Less ability to remove
  glucose from blood!
• How does receptor up/down regulation explain why
  a drug may work at first, but not later?
• Hormone/Second Messenger Destruction Cells can
  also learn to destroy hormones and 2nd messengers
  more rapidly.
• Phosphodiesterase stops cAMP activity
• If a cell makes more PDE, you need to use more
  hormone to get effect!

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Cellular responses to hormones/drugs can change.
WHY IS THIS IMPORTANT????

• Dosage Physiological vs. Pharmacological
• How much is created and how much is required for
  what effects?
• Why might low level or high level hormone
  releases give different effects?
• Consider ADH effects with moderate or severe
  dehydration!
• Do two hormones work together or against each
  other?
• Synergistic (same) Effects Oxytocin and
  Prostaglandins work together in uterus!
• Antagonistic (against) Effects Glucagon vs.
  Insulin work against each other in liver!

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The pituitary gland is composed to two parts 1)
Neurohypophysis connected to hypothalamus by
axons.2) Adenohypophysis a portal system of
fenestrated capillaries supplies it with
hypothalamic releasing hormones.
Fenestration make these 1st capillaries very
permeable to the releasing hormones!!!
The neurohypophysis consists of a set of nerve
endings that release their hormones directly into
the blood. These hormones are synthesized in the
hypothalamus and travel via axonal TX.
Fenestrations also make this second set permeable
too!
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HOW DOES THE HYPOTHALMUS REGULATE PITUITARY
FUNCTION?

• Hypothalamus location floor and walls of 3rd
  Ventricle
• Hypophysis (pituitary) sits in the sella turica
  of the sphenoid below the hypothalamus.
• Hypothalamus and Hypophysis are connected by the
  infundibulum or stalk.
• Posterior Pituitary (Neurohypophysis) Direct
  release of hormones made in hypothalamus into
  fenestrated capillaries.
• Anterior Pituitary (Adenohypophysis)
  Hypothalamic releasing/inhibiting hormones
  required to promote release a second hormone from
  Ant. Pit (REQgt Portal Circulatory Structure!)

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Posterior Pituitary What pituitary hormones
regulate child birth and water homeostasis/blood
pressure?

• Two hypothalamic nuclei create two sets of
  hormones that are released into the blood stream
  at the neurophypophysis
• Paraventricular Nucleus Oxytocinchild
  birth/milk
• Saladin claims importance questionable Be
  Careful!
• Days before birth OT receptors in uterus
  increase!
• Increased receptors?stronger SMC
  contractions?Delivery!
• OTgtPLgtgtIP3gtgtCagtgtContraction and Prostaglandins
• Supraventricular Nucleus Anti-Diuretic Hormone
  (ADH or Vasopressin)? Maintains blood pressure!
• Water Reabsorption in kidney?Blood
  Volume?Blood Pressure
• Constrictor effect only at very high levels?
  Blood Pressure.
• Adjusts plasma volume and osmolarity.
• Diabetes Insipidus often occurs when lesions form
  in tracts
• Note no glucose in the urine!

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THE HYPOTHALMUS CONTROLS ANTERIOR PITUITARY
FUNCTION WITH RELEASING/INHIBITING HORMONES THAT
ONLY WORK IF THE PORTAL SYSTEM IS INTACT!

• Releasing/Inhibiting hormones released to
  blood/capillaries in hypothalamus (portal system
  1) and pulled out at second capillary bed in
  anterior pituitary.
• 6 Ant. Pit. Hormones FSH,LH,TSH,ACTH,PRL,GH
• Respective Hypothalamic Hormones Control Release
• 1) Thyrotropin Releasing Hormone (TRH)?TSH and
  PRL
• 2) Prolactin Releasing Factor (PRF)?PRL
• 3) Prolactin Inhibitory Factor (PIF)?-PRL
• 4) Corticotropin Releasing Factor(CRH)?ACTH
• 5) Growth Hormone Releasing Hormone (GnRH)?GH
• 6) Gonadotropin Releasing Hormone?FSH/LH
• 6) Somatostatin (GNIH) ? -GH AND -TSH

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FOUR TROPHIC HORMONES ARE RELEASED FROM THE
ANTERIOR PITUITARY ACTH, PRL,TSH AND GH

• Adrenocorticotrophic hormone (ACTH)-Stimulates
  adrenal cortex and glucocorticoid secretion for
  stress management.
• Prolactin-Stimulates milk synthesis following
  birth.
• Thyroid stimulating Hormone (TSH)-Stimulates
  thyroid gland to release T3/T4 and create a
  calorigenic state in bodygtgtgtHEAT or growth dung
  infancy
• Growth Hormone (GH)-Stimulates cell division,
  protein synthesis and bone growth Promotes
  FA metabolism saves glucose for glycogen
  synthesis and storage. Related to Gigantism,
  Acromegally and Dwarfism
• Pituitary tumors can occur in a pituitary cell
  line for anyone of these hormones, this type of
  cancer is very tough to treat with radiation of
  surgery! WHY???

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How does Prolactin play a role in making the
cows come home?
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THE TWO ANTERIOR PITUITARY GONADOTROPHIC HORMONES
PROMOTE SEX STEROID SYNTHESIS.

• LH is Luteinizing Hormone
• LH (not FSH) Stimulates testosterone production
  by Leydig cells in testes
• Stimulates initial estrogen secretion from
  follicle and corpus luteum
• FSH is Follicle Stimulating Hormone
• FSH (not LH) Stimulates sperm maturation at
  testes
• -Stimulates egg maturation/ovulation
• Classic Feedback Loop in Women leading to
  Ovulation
• GnRH? FSH and LH ? follicle/estradiol?GnRH? LH
  Surge ?Ovulation?Corpus luteum makes progesterone
  and some estradiol to maintain endometrium

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GONADS RESPOND TO FSH/LH AND SECRETE MANY SEX
STEROIDS WITH TWO IMPORTANT ONES BEING ESTRADIOL
AND TESTOSTERONE.

• Males produce testosterone in response to
  LH Promotes Protein Synthesis, Stops growth
  plate DHEA (dehydroxyepandiosterone) is a
  precursor for testosterone synthesis
• FSH release is inhibited because high levels of
  testosterone inhibit GnRH release from
  hypothalamus
• Females produce estrogen in response to
  FSH Estradiol causes follicular
  maturation/release Newly formed corpus luteum
  makes progestrone in addition to continued
  estrogen
• Menopause occurs later in life when even
  extremely high levels of FSH are unable to
  increase estradiol secretion and follicular
  maturation.

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Sex Steroid Synthesis in gonads of males and
females is very similar, difference is that in
females testosterone is further metabolized to
make estradiol. Smaller amounts of synthesis also
occurs in the zona reticularis of the adrenal
cortex.
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THE PINEAL GLAND IS OUR BIOLOGICAL CLOCK IT
CONTROLS CIRCADIAN AND SEASONAL RHYTHMS.

• Located in back/bottom area of brain of mammals
  on roof of third ventricle.
• Circadian Rhythms are daily cycles of hormone
  production.
• Rhythms can also occur on a monthly and yearly
  cycle.
• During the day a modified amino acid called
  serotonin is released (wakefulness).
• Wakefulness is the opposite of depression
• Many antidepressant drugs work by reducing
  serotonin destruction/removal improve mood and
• At night serotonin is converted into melatonin
  which is a hormone that causes drowsiness and
  sleep.
• Why does honey on toast help you wake up or
  dream?
• This is source of jet-lag symptoms!

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CIRCADIAN RHYTHMS OF HORMONE PRODUCTION CAN BE
VERY IMPORTANT IN EXPLAINING WHY ASTHMA OR HEART
ATTACKS ARE MORE COMMON AT CERTAIN TIMES OF THE
DAY.

• 1) Remember that EPI and NE help dilate cardiac
  blood vessels and airways
• How does this help during exercise?
• 3) Remember that cortisol helps constrict
  airways!
• How does this help clean air when you sleep?
• 4) When are asthma/heart attacks more common?
• When is cortisol or EPI/NE more prominent?
• Many anti-depressive drugs mimic
  serotonin/melatonin
• Many anti-depressive drugs prevent the
  destruction or removal of serotonin (PROZAC
  blocks pumps).
• Seasonal Affective Disorder and PreMenstrual
  Syndrome are two classic examples of disorders
  that may respond to modified serotonin release,
  uptake or destruction.