ENDOCRINE SYSTEM

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ENDOCRINE SYSTEM
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Nervous Vs. Endocrine Systems

• ENDOCRINE
• controlling system
• releases chemical messengers-hormones
• regulated by negative feedback
• goal-Homeostasis
• effects appear slow
• require hours, months or years
• effects-long lasting
• regulates long acting changes such as metabolic
  activity

• NERVOUS
• controlling system
• releases chemical messengers-neurotransmitters
• regulated by negative feedback
• goal-Homeostasis
• effects appear fast
• can produce effects in milliseconds
• effects-short duration
• useful for crisis control

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Endocrine Communication

• changes cellular operations by changing
• types of enzymes or proteins
• quantities of enzymes or proteins
• activities of enzymes or structural proteins
• accomplishes with hormones
• substances released from one tissue and
  transported via blood stream to have effects on
  distant tissues

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Endocrine System

• composed of endocrine glands
• small, ductless glands
• widely scattered throughout body
• release secretions-hormones into circulatory
  system
• hormones make contact with all cell types
• influence only target cells
• contain specific protein receptors on membranes
  or inside cell to which hormones can bind
• some endocrine glands are discrete organs
• pituitary thyroid
• others contain discrete areas of endocrine tissue
  within their structure
• islet of Langerhans in pancreas

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Chemical Classes of Hormones

• Lipid Soluble
• Steroids
• Thyroid Hormone
• Nitric Oxide
• Water Soluble
• Amines
• Peptides
• Proteins
• Eicosanoid

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Steroid Hormones

• derived from cholesterol
• Estrogen
• Progesterone
• Testosterone
• Adrenocortical hormones
• transported bound to blood transport proteins
• keeps them in circulation longer

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Thyroid Hormone

• Made by adding Iodine to the amino acid tyrosine
• Soluble in lipid due to the ring structure

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Peptide/Protein Hormones

• Peptide
• chains of 3 to 49 amino acids
• Protein
• chains of 50 -200 amino acids

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Amines

• made from amino acids
• retain an amino group
• epinephrine
• norepinephrine

Epinephrine
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Eicosanoids

• derived from fatty acid
• Arachidonic acid
• Prostaglandins
• Leukotrienes
• Local hormones

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Mechanisms of Action

• Hormones change cellular operations
• by stimulating synthesis of enzymes or structural
  proteins
• by activating genes
• by changing rate of transcription or translation
• by turning existing enzymes on or off
• come into contact with all types of body cells
• only have effects at particular target cells
• target cells have receptors for particular
  hormones
• found on cell membrane or inside cell

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Lipid Soluble Hormones- Direct Gene Activation

• soluble in lipid
• can cross cell membrane
• bind to receptors on inside of cell
• in cytoplasm or nucleus
• forming hormone-receptor complex

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Direct Gene Activation Steps

• 1-hormone diffuses from blood to cell
• 2-hormone enters cell
• 3-hormone binds to receptor forming
  receptor-hormone complex
• 4-alters gene expression-mRNA is made
• 5-mRNA leaves nucleus-directs protein synthesis
• 6-new protein alters metabolic activities of
  other protein

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Water Soluble Hormones-Second Messenger Mechanism

• cannot enter target cells
• must stimulate target cells indirectly
• second-messenger system
• receptors embedded in cell membrane
• Hormone-first messenger
• responsible for appearance of second
  messenger-produces effects of hormone
• Second messengers include
• cAMP
• cGMP
• Ca
• second messenger activates or inhibits cofactors
  which changes rate of metabolic reactions

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Second Messenger Mechanism

• hormone binds to plasma membrane receptor
• activates G protein-regulatory molecule
• activated G protein activates adenlyate cyclase
• Activatged adenylate cyclase converts ATP to cAMP
  (cyclic AMP)
• cAMP is the second messenger
• activates protein kinase
• catalyzes reactions
• degraded by phosphodiesterase

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Control of Endocrine Activity

• neural impulses
• hormones
• humoral stimuli
• changes in blood chemistry
• changes in extracellular body fluids

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Neural Control

• nerve fibers stimulate hormone release
• neuroendocrine system
• Example-milk-let down reflex
• stimulation of udder? neural signals? spinal
  cord? brain? secretory neurons in posterior
  pituitary? oxytocin released?blood flows through
  venous system to heart?lungs? back to heart?
  arterial system?udders?milk let down

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Hormonal Control

• hormones cause the release of other hormones
• releasing hormones from hypothalamus travel to
  anterior pituitary causing cells there to release
  tropic hormones
• GnRh? LH FSH?ovaries?secrete hormones
• ACTH?CRH?adrenal cortex?releases hormones

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Humoral Control

• changing blood levels of ions nutrients cause
  hormones to be released
• parathyroid gland monitors Ca concentration
• when low secretes parathyroid hormone?Ca
  increases
• insulin is released by pancreas due to humoral
  stimulus of too much glucose in blood

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Hypothalamus

• forms floor walls of third ventricle of brain
• responsible for regulation of primitive body
  functions
• reproduction, hunger thirst
• many functions are carried out by pituitary gland
• master gland

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Hypothalamus-Pituitary

• hypothalamus secretes regulatory hormones
  (releasing hormones) which control endocrine
  cells in anterior lobe of pituitary
• also manufactures hormones which travel via
  hypothalamus-hypophyseal tract to be stored in
  posterior pituitary
• hypothalamus has direct neural control over
  endocrine cells in adrenal medulla via
  sympathetic nervous system
• neuroendocrine reflex

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Hypophyseal PortalSystem

• Adenohypohysis has no direct connection to
  hypothalamus
• connected by hypophyseal portal system
• typically arteries take blood from heart to
  capillaries veins from capillaries to heart
• portal system-blood flows from one capillary
  network into portal vein? then to secondary
  capillary network before returning to heart.
• arrangement ensures all blood entering portal
  vessels will reach target cells before entering
  general circulation

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Hypothalamic Hormones

• 2 neurohormones
• oxytocin antidiruretic hormones
• stored in pituitary
• 5 regulating hormones-releasing hormones (RH)
• stimulate synthesis secretion of other hormones
  in anterior pituitary
• 2 inhibiting hormones (IH)
• inhibit synthesis secretion of other hormones
  from anterior pituitary

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Hypothalamic Control of Anterior Pituitary

• negative feedback loops
• Hypothalamus? releasing hormones ?
  adenohypophysis? tropic or trophic hormone ?
  stimulate other endocrine glands or tissues
• hormones from other endocrine glands feedback to
  turn off their own production

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Pituitary Gland-Hypophysis

• located in sella turcica-depression in sphenoid
  bone
• size shape of a pea
• connects to hypothalamus by infundibulum
• composed of two parts
• Adenohypothesis
• Neurohypothesis
• separate functions
• separate anatomy

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Anterior Pituitary Gland

• three discrete regions
• pars distalis
• largest most anterior
• pars tuberalis
• wraps around infundibulum
• pars intermedia
• narrow band bordering the posterior pituitary
  lobe
• atrophies before birth

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Growth Hormone-Somatotropin

• secreted by somatotropes
• promote protein synthesis
• influence carbohydrate metabolism by decreasing
  glucose uptake
• promote production of somatomedins or
  IGFs-Insulin like growth factors
• stimulate uptake of amino acids incorporation
  into proteins
• overall increase growth rate of skeleton
  skeletal muscles during childhood teenage years
• in adults help maintain muscle bone mass help
  to promote healing tissue repair

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Growth Hormone Secretion

• GHRH (growth hormone releasing hormone)
  stimulates release of GH
• GHIH (growth hormone inhibiting factor) or
  somatostatin inhibits release
• GHIH-triggered by feedback of GH IGFs
• as GH increases-inhibits its own release

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Growth Hormone
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TSH-Thyroid Stimulating Hormone

• TRH (thyrotropin releasing hormone) is made by
  hypothalamus
• ?thyrotrope cells of anterior pituitary?
  TSH?thyroid gland? thyroid hormone
• thyroid hormone feeds backs on TRH TSH?inhibits
  secretion

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ACTH-Corticotrophin

• released from corticotrope cells of anterior
  pituitary due to stimulation from CRH
  (corticotropin releasing hormone) made by
  hypothalamus
• ACTH?adrenal cortex?
• glucocorticorticoids (especially cortisol)
• glucocorticoids feedback to block secretion of
  CRH ACTH

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Gonadotropins-FSH LH

• regulate activities of gonads
• hypothalamus releases gonadotropin releasing
  factors (GnRH)?anterior pituitary?LH FSH
• FSH (follicle stimulating hormone) promotes
  follicle development in females with LH
  stimulates estrogen secretion
• in males FSH stimulates sperm differentiation
• production of GnRH is inhibited by inhibin
• released by cells in gonads
• LH?induces ovulation promotes progestin
  secretion by ovaries
• in males LH-also called ICSH or interstitial cell
  stimulating hormone stimulates interstitial cells
  of testes?androgens
• gonadal hormones feedback to suppress FSH LH
  release

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Prolactin-PRL

• released from anterior pituitary due to
  stimulation by PRH made by hypothalamus
• PRL targets lactotropes in mammary glands?milk
  production
• PRL helps regulate androgen production in males
  by making interstitial cells more sensitive to
  LH.
• hypothalamus?PIH or prolactin inhibiting hormone
  ? prevents prolactin secretion
• circulating prolactin stimulates PIH production
  inhibits PRH

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MSH-Melanocyte Stimulating Hormone

• made by pars intermedia
• stimulates melanocytes to make melatin
• no circulating MSH in adults
• melanin receptors in the brain suggests it is
  involved in brain activity

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Posterior Pituitary-Neurohypophysis

• neurons of supraoptic (ADH) paraventricular
  (oxytocin) nuclei make hormones
• made in hypothalamus
• transported to pituitary along nerve axons
• stored in posterior pituitary
• released from posterior pituitary on demand in
  response to nerve impulses from same
  hypothalamic neurons that made them

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ADH-Vasopression or Antidiuretic Hormone

• involved in water balance
• released in response to increases in electrolyte
  concentrations in blood
• neurons responsible for release- osmoreceptors
• solutes concentrated? osmoreceptors excite
  supraoptic nuclei?synthesis release of ADH
• Target-kidney tubules?reabsorb water from
  urine?less urine?blood volume increases?blood
  pressure increases
• solute concentration decreases, osmoreceptors?end
  ADH release
• high concentrations of ADH produce
  vasoconstriction primarily of visceral blood
  vessels-thus it is named vasopressin

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Oxytocin

• produces smooth muscle contraction in uterus
  breasts
• released in high amounts during childbirth when
  nursing
• uterus stretches?impulse to hypothalamus?oxytoxin
  made released from posterior pituitary?
  blood?contractions increase-positive feed back
  control
• also acts for milk ejection via neuroendocrine
  reflex-milk let down reflex
• suckling (stimulus)?sensory neurons?
  hypothalamus?ocytoxin released?myoepithelial
  cells?release milk
• also believed to be cuddle hormone which promotes
  nurturing affectionate or bonding behavior

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Pituitary Gland Review

• secretes nine peptide hormones
• 7 from anterior pituitary
• 2 from posterior pituitary

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Thyroid Gland

• largest endocrine gland
• located in anterior neck
• 2 lobes connected by an isthmus
• contains large number of follicles
• lined by simple cuboidal epithelium or follicular
  cells
• follicle cells surround a follicular cavity which
  stores colloid

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Thyroid Hormone Formation

• 1. Iodide Trapping follicle cells trap I- by
  active transporting the ion from the blood
• 2. Thyroglobulin (TGB) Made ribosomes make TGB
  packaged by Golgi into vesicles
• 3. TGB released vesicles undergo exocytosis and
  release TGB into the lumen of the follicle
• 4. Iodide oxidation I- loses an electron ?I2
• 5. Iodination of tyrosine I2 binds to tyrosine
• attachment of 1?monoiodotyrosine
• attachment of 2?diiodotyrosine
• once iodine binds-colloid
• 6. Coupling of T1 T2
• T2 T1 are linked by to produce
  T3-triiodothyronine T4-tetraiodothyronine-
  thyroxin
• 7. Pinocytosis Digestion of Colloid droplets of
  colloid enter the cell by pinocytosis and bind to
  lysosome
• Breaks off T3 T4
• 8. Secretion of Hormone thyroid hormones are
  lipid soluble diffuse through membrane
• 9. Transport of Hormone bind to TBG (thyroxine
  binding globulins) to be carried to tissues

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Release of Thyroid Hormone

• thyroxine levels fall? hypothalamus ? TRH?
  pituitary?TSH? thyroid cells? thyroid hormones
• 90 is T4-major thytoid hormone
• 10 is T3
• T3 is more potent and responsible for effects of
  thyroid hormone

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Functions of Thyroid Hormone

• major metabolic hormones
• Increase BMR (basal metabolic rate) which raises
  use of oxygen
• calorigenic effect-increases heat production
• involved in long-term regulation of metabolic
  turnover
• effects almost every cell in body except-adult
  brain, spleen, testes, uterus and thyroid

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Control of Thyroid Hormone
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Parafollicular Cells of Thyroid

• secrete calcitonin
• lowers blood Ca levels
• Ca homeostasis is essential for nerve
  transmission, muscle contraction blood clotting
• too low?Na permeability increases?cells become
  more excitable
• calcium levels too high, hypercalcemia?Na
  permeability decreases? membranes less excitable

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Calcitonin

• C cells respond to Ca concentrations in blood
• increased Ca concentration ?increased
  calcitonin
• at skeleton? inhibits osteoclast activity?
  decreases Ca release from bone

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Parathyroid Glands

• 4 embedded in posterior thyroid
• two cell types
• oxyphil cells
• unknown function
• chief or principal cells
• secrete PTH (parathyroid hormone or parathormone)

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Parathyroid Hormone Targets

• single most important agent in controlling Ca
  balance
• chief cells monitor Ca levels
• lowered blood Ca-hypocalcemia
• stimulates secretion
• increases Ca in blood by stimulating skeleton,
  kidneys intestines
• Skeleton?PTH stimulates osteoclasts to digest
  bone matrix? releases Ca
• Kidneys?PTH enhances reabsorption of Ca
• PTH increases Ca by enhancing synthesis of
  calcitriol by the kidney which enhances Ca
  absorption by gut

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Adrenal or Suprarenal Glands

• pyramid shaped organs-top of kidneys
• 2 parts
• structurally functionally different
• inner part-adrenal medulla
• part of sympathetic nervous system
• makes epinephrine norepinephrine
• Outer-adrenal cortex
• Makes steroid hormones called corticosteroids or
  adrenocortical steroids
• vital to life

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Adrenal Cortex

• 3 regions or zones
• Zona Glomerulosa
• outer region
• composed of globular cell clusters called
  glomeruli
• mineralocorticoids
• Zona Fasciculata
• middle zone
• cells form in linear cords
• glucocorticoids
• Zona reticularis
• inner zone
• cells form net like arrangement
• gonadocorticoids

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Zona Glomerulosa

• Mineralocorticoids
• control mineral water balance in extracellular
  fluids-particularly Na K
• Aldosterone
• main mineralocorticoid
• maintains Na balance by reducing excretion of Na
  increasing elimination of K
• primary target-distal kidney tubule? stimulates
  reabsorption of Na water from urine
• enhances Na absorption from sweat, saliva and
  gastric juices
• Na ion regulation is critical to overall body
  homeostasis
• where Na goes water follows via osmotic
  reabsorption
• therefore secondary effect of mineralocorticoids
  is reabsorption of water
• can lead to blood volume blood pressure changes
• Aldosterone release is stimulated by rising K
  levels, low Na levels, decreasing blood volume
  blood pressure
• also released in response to angiotensin II
• hormone made released by kidneys

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Zona Fasciculata

• produce glucocorticoids
• influence glucose metabolism
• important in helping to resist stressors
• absolutely essential to life
• main one-cortisol or hydrocortisone
• primary metabolic effect is gluconeogenesis\
• formation of glucose from non-carbohydrate
  sources
• helps body adapt to intermittent food intake by
  keeping blood sugar levels constant
• does so by breaking down adipose tissues?fatty
  acids proteins?amino acids.
• glucocoricoids enhance epinephrines
  vasoconstrictive effects?rise in blood pressure
  and circulatory efficiency
• helps maintain blood volume by preventing a shift
  of water into tissue cells
• Too much?depresses cartilage bone formation,
  inhibits inflammation, depresses immune system,
  and promotes changes in cardiovascular, neural
  and gastrointestinal functions
• inhibit activities of WBCs

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Cortisol Regulation

• regulated by negative feedback
• CRH from hypothalamus ?ACTH from anterior
  pituitary?zona fasciculata?cortisol
• increased cortisol ?hypothalamus anterior
  pituitary ?prevents CRH release ACTH production
  

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Zona Reticularis

• Gonadocorticoids
• DHEA- dehydroepiandrosterone
• sustains libidio (sex drive)
• release stimulated by ACTH

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Adrenal Medulla

• secretes catecholamines-epinephrine
  norepinephrine and dopamine
• made by chromaffin cells
• sympathetic activity increases rate of release
• Stress exercise? hypothalamus?medulla?hormones
  ?fight or flight reaction
• Increase in heart rate and blood pressure

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Pancreas

• elongated, spongy mixed gland
• exocrine (98) endocrine (2) functions
• located partially behind stomach in abdomen
• exocrine cells are found in clusters called
  pancreatic acini
• secrete alkaline, enzyme rich fluid used in
  digestion
• endocrine pancreas is found scattered throughout
  gland in groups of cell clusters called Islets of
  Langerhans

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Islets of Langerhans

• Alpha cells
• secrete glucagon
• hyperglycemic effect
• increases blood glucose levels by increasing
  glycogenolysis in liver
• Beta cells
• secrete insulin
• hypoglycemic effect
• Decreases blood glucose
• Delta cells
• synthesize somatostatin when blood glucose, fatty
  acids and amino acid levels rise after eating
• inhibits digestive functions in blood pancreas
• suppresses release of glucagon insulin by the
  neighboring alpha alpha beta cells.
• F Cells
• secrete pancreatic polypeptide
• Inhibits somatostatin

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Glucagon

• secretion prompted by humoral stimuli
• falling blood sugar levels rising amino acid
  levels
• secretion suppressed by rising blood sugar
• in liver skeletal muscle stimulates break down
  of glycogen into glucose- glycogenolysis
• stimulates break down of triglycerides in adipose
  tissue
• stimulates glucose production from lactic acid
  other non-carbohydrate sources-gluconeogenesis in
  liver
• Result?less glucose use more glucose
  release?increases blood glucose

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Insulin

• decreases blood glucose levels by increasing
  rate of glucose uptake use
• one effect is to enhance glucose absorption
  utilization
• accelerates glucose use enhances ATP production
• stimulates glycogen formation in skeletal muscle
  and liver cells
• stimulates amino acid absorption and protein
  synthesis
• stimulates triglyceride formation in adipose
  tissue

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Gonads

• Testes
• Androgens
• testosterone-major one
• Ovaries
• Estrogens

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Testosterone Functions

• maturation of reproductive organs
• appearance maintenance of secondary sex
  characteristics
• effects metabolic activities
• stimulates protein synthesis muscle growth

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Estrogen Functions

• maturation of reproductive organs
• Development maintenance of secondary sex
  characteristics

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Pineal Gland

• tiny, pine coned shaped structure hanging from
  roof of third ventricle
• secretes melatonin at night
• rises falls in diurnal cycle
• peaks at night? inducing sleep
• lowest during day
• pineal receives information regarding intensity
  duration of day light via retina?suprachiasmatic
  nucleus in hypothalamus?pineal gland?melatonin
• responsible for setting circadian rhythm or
  daily-cycles

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Endocrine Tissues of Other Organs

• Heart-atrium
• ANP-atrial natriuretic peptide
• promotes loss of Na water at kidneys inhibits
  renin release secretion of ADH aldosterone
• net result is reduction of blood volume
  pressure.
• Skin-keratinocytes
• Vitamin D3-first step in production of calcitriol
• hormone that raises blood calcium levels
• Stomach Small Intestine
• Enteroendocrine cells secrete about 10 enteric
  hormones
• Coordinate different regions glands of
  digestive system with each other
• Kidney
• Erythropoietin
• released in response to low O2 levels? stimulates
  RBCs production
• renin
• cleaves angiotensinogen?angiotensin II ?adrenal
  cortex?aldosterone ?increases blood volume
  pressure
• Thymus
• thymopoietins thymosins
• important in development of T lymphocytes
  important in the immune response
• Adipose tissue