Hypothalamus and Pituitary Hypothalamus and Pituitary Th

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Hypothalamus and Pituitary
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Hypothalamus and Pituitary

• The hypothalamus-pituitary unit is the most
  dominant portion of the entire endocrine system.
• The output of the hypothalamus-pituitary unit
  regulates the function of the thyroid, adrenal
  and reproductive glands and also controls somatic
  growth, lactation, milk secretion and water
  metabolism.

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Hypothalamus and Pituitary

• Pituitary function depends on the hypothalamus
  and the anatomical organization of the
  hypothalamus-pituitary unit reflects this
  relationship.
• The pituitary gland lies in a pocket of bone at
  the base of the brain, just below the
  hypothalamus to which it is connected by a stalk
  containing nerve fibers and blood vessels. The
  pituitary is composed to two lobes-- anterior and
  posterior

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Posterior Pituitary neurohypophysis

• Posterior pituitary an outgrowth of the
  hypothalamus composed of neural tissue.
• Hypothalamic neurons pass through the neural
  stalk and end in the posterior pituitary.
• The upper portion of the neural stalk extends
  into the hypothalamus and is called the median
  eminence.

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Anterior pituitary adenohypophysis

• Anterior pituitary connected to the hypothalamus
  by the superior hypophyseal artery.
• The antererior pituitary is an amalgam of hormone
  producing glandular cells.
• The anterior pituitary produces six peptide
  hormones prolactin, growth hormone (GH), thyroid
  stimulating hormone (TSH), adrenocorticotropic
  hormone (ACTH), follicle-stimulating hormone
  (FSH), and luteinizing hormone (LH).

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Hypothalamus and pituitary gland
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Hypothalamus and pituitary gland
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Regulation of Hypothalamus
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Anatomical and functional organization
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Hypothalamic releasing factors for anterior
pituitary hormones

• Travel to adenohypophysis via hypophyseal-portal
  circulation
• Travel to specific cells in anterior pituitary to
  stimulate synthesis and secretion of trophic
  hormones

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Hypothalamic releasing hormones
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Characteristics of hypothalamic releasing
hormones

• Secretion in pulses
• Act on specific membrane receptors
• Transduce signals via second messengers
• Stimulate release of stored pituitary hormones
• Stimulate synthesis of pituitary hormones
• Stimulates hyperplasia and hypertophy of target
  cells
• Regulates its own receptor

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Anterior pituitary

• Anterior pituitary connected to the hypothalamus
  by hypothalmoanterior pituitary portal vessels.
• The anterior pituitary produces six peptide
  hormones
• prolactin, growth hormone (GH),
• thyroid stimulating hormone (TSH),
• adrenocorticotropic hormone (ACTH),
• follicle-stimulating hormone (FSH),
• luteinizing hormone (LH).

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Anterior pituitary cells and hormones
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Hypothalamus and anterior pituitary
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Anterior pituitary hormones
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Feedback regulation of hypothalmus/pituitary

• A prominent feature of each of the hormonal
  sequences initiated by the hypothalamic releasing
  hormones is negative feedback exerted upon the
  hypothalamic-pituitary system by the hormones
  whose production are stimulated in the sequence.

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Hypothalamus-pituitary axis
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Feedback control
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Feedback control of thyroid function
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Feedback and restoration of homeostasis
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Feedback control of growth hormone
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Growth hormone vs. metabolic state

• When protein and energy intake are adequate, it
  is appropriate to convert amino acids to protein
  and stimulate growth. hence GH and insulin
  promote anabolic reactions during protein intake
• During carbohydrate intake, GH antagonizes
  insulin effects-- blocks glucose uptake to
  prevent hypoglycemia. (if there is too much
  insulin, all the glucose would be taken up).
• When there is adequate glucose as during
  absorptive phase, and glucose uptake is required,
  then GH secretion is inhibited so it won't
  counter act insulin action.

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Growth hormone vs. metabolic state

• During fasting, GH antagonizes insulin action and
  helps mediate glucose sparing, ie stimulates
  gluconeogenesis
• In general, duing anabolic or absorptive phase,
  GH facilitates insulin action, to promote
  growth.
• during fasting or post-absorptive phase, GH
  opposes insulin action, to promote catabolism or
  glucose sparing

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Growth hormone and metabolic state
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ACTH adrenocorticotropic hormone synthesis and
regulation of secrtion

• Produced in corticotrophs
• ACTH is produced in the anterior pituitary by
  proteolytic processing of Prepro-opiomelanocortin
  (POMC).
• Other neuropeptide products include b and g
  lipotropin, b-endorphin, and a-melanocyte-stimulat
  ing hormone (a-MSH).
• ACTH is a key regulator of the stress response

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ACTH synthesis
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ACTH

• ACTH is made up of 39 amino acids
• Regulates adrenal cortex and synthesis of
  adrenocorticosteroids
• a-MSH resides in first 13 AA of ACTH
• a-MSH stimulates melanocytes and can darken skin
• Overproduction of ACTH may accompany increased
  pigmentation due to a-MSH.

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Addisons Disease

• Disease in which patients lack cortisol from zona
  fasiculata, and thus lacks negative feedback that
  suppresses ACTH production
• Result overproduction of ACTH
• Skin color will darken
• JFK had Addisons disease and was treated with
  cortisol injections

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b-endorphin

• Produced as a result of ACTH synthesis
• Binds to opiate receptors
• Results in runners high
• Role in anterior pituitary not completely
  understood
• One of many endogenous opiods such as enkephalins

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Regulation of ACTH secretion
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Regulation of ACTH

• Stimulation of release
• CRH and ADH
• Stress
• Hypoglycemia
• CRH and ADH both synthesized in hypothalamus
• ADH is released by posertior pituitary and
  reaches anterior pituitary via inferior
  hypophyseal artery.

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ACTH

• Circadian pattern of release
• Highest levels of cortisol are in early AM
  following ACTH release
• Depends on sleep-wake cycle, jet-lag can result
  in alteration of pattern
• Opposes the circadian pattern of growth hormone
  secretion

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Regulation of ACTH
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ACTH

• Acts on adrenal cortex
• stimulates growth of cortex (trophic action)
• Stimulates steroid hormone synthesis
• Lack of negative feedback from cortisol results
  in aberrantly high ACTH, elevated levels of other
  adrenal corticosteroids adrenal androgens
• Adrenogenital syndrome masculization of female
  fetus

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Glycoprotein hormones

• LH, FSH, TSH and hCG
• a and b subunits
• Each subunit encoded by different gene
• a subunit is identical for all hormones
• b subunit are unique and provide biological
  specificity

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Glycoprotein hormones
Glycoprotein hormones contain two subunits, a
common a subunit and a distinct b subunit TSH,
LH, FSH and hCG.
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Gonadotrophs

• Cells in anterior pituitary that produce LH and
  FSH
• Synthesis and secretion stimulated by GnRH major
  effect on LH
• FSH secretion controlled by inhibin
• Pulsitile secretion of GnRH and inhibin cause
  distinct patterns of LH and FSH secretion

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LH/FSH

• Pulsatile pattern of secretion
• LH pulses are biphasic (every 1 minute, then
  large pulse at 1 hour)
• FSH pulses are uniphasic
• Diurnal LH/FSH more pronounced during puberty
• Cyclic in females ovarian cycle with LH surge at
  time of ovulation
• Males are not cyclic, but constant pulses of LH
  cause pulses of testosterone to be produced

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Pulsitile secretion of GnRH and LH
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Regulation of LH/FSH

• Negative feed-back
• Inhibin produced by testes and ovaries Decreases
  FSH b-subunit expression
• Testosterone from Leydig cells synthesis
  stimulated by LH, feedsback to inhibit GnRH
  production from hypothalamus and down-regulates
  GnRH receptors
• Progesterone suppresses ovulation, basis for
  oral contraceptives. Works at both the level of
  pituitary and hypothalamus.

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Regulation of LH/FSH

• Dopamine, endorphin, and prolactin inhibit GnRH
  release.
• Prolactin inhibition affords post-partum
  contraceptive effect
• Overproduction of prolactin via pituitary tumor
  can cause amenorrhea shuts off GnRH
• Treated with bromocryptine (dopamine agonist)
• Surgical removal of pituitary tumor

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Regulation of LH/FSH

• Positive feedback
• Estradiol at high plasma concentrations in late
  follicular phase of ovarian cycle stimulates GnRH
  and LH surge triggers ovulation

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Regulation of gonadotropin secretion
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Thyrotrophs

• Site of TSH synthesis
• Pattern of secretion is relatively steady
• TSH secretion stimulated by TRH
• Feedback control by T3 (thyroid hormone)

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Feedback control of thyroid function
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Lacotrophs

• Site of production of prolactin
• Lactogenesis (milk synthesis) requires prolactin
• Tonically inhibited
• Of the anterior pituitary hormones, the only one
• Multifactoral control, balance favors inhibition
• Dopamine inhibits prolactin
• Prolactin releasing hormone is TRH
• Ocytocin also stimulates prolactin release
• Estradiol enhances prolactin synthesis

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Prolactin

• Stimulates breast development and lactogenesis
• May be involved in development of Leydig cells in
  pre-pubertal males
• Immunomodulatory effects stimulates T cell
  functions
• Prolactin receptors in thymus

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Posterior pituitary hormones ADH (AVP) and
Oxytocin (really hypothalamic hormones)

• Both are synthesized in the cell bodies of
  hypothalamic neurons
• ADH supraoptic nucleus
• Oxytocin paraventricular nucleus
• Both are synthesized as preprohormones and
  processed into nonapeptides (nine amino acids).
• They are released from the termini in response to
  an action potential which travels from the axon
  body in the hypothalamus

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Hypothalamus and posterior pituitary
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Structures of ADH and oxytocin
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Oxytocin stimulates myoepithelial contractions

• In uterus during parturition
• In mammary gland during lactation

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Oxytocin milk ejection from lactating mammary
gland

• suckling is major stimulus for release.
• sensory receptors in nipple connect with nerve
  fibers to the spine, then impulses are relayed
  through brain to PVN where cholinergic synapses
  fire on oxytocin neurons and stimulate release.

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Oxytocin uterine contractions

• Reflexes originating in the cervical, vaginal and
  uterus stimulate oxytocin synthesis and release
  via neural input to hypothalamus
• Increases in plasma at time of ovulation,
  parturition, and coitus
• Estrogen increases synthesis and lowers threshold
  for release

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Oxytocin secretion is stimulated by nursing
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ADH conserve body water and regulate tonicity of
body fluids

• Also known as vasopressin
• Regulated by osmotic and volume stimuli
• Water deprivation increases osmolality of plasma
  which activates hypothalmic osmoreceptors to
  stimulate ADH release

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Regulation of ADH secretion
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ADH increases renal tubular absorption of water
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ADH and plasma osmolality
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ADH and blood pressure