THE BREAST, PROLACTIN

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THE BREAST, PROLACTIN LACTATION
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The Breast

• Modified apocrine sweat gland
• Multiple lobules, aveoli and myoepithelial cells
• Connected by a series of ducts
• Exit via 15-20 apertures in areola

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The Breast

• Proliferation and regression of ductal tissue
  occurs with each menstrual cycle
• Proliferative changes reach a peak late in luteal
  phase
• Regression follows each menses
• Most molding and contour differences are
  determined by fat

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The Breast

• Estrogen stimulates breast growth at puberty
• Full differentiation and function involves
  estrogen, progesterone, insulin, cortisol,
  thyroxine, prolactin and growth hormone
• Mild deficiencies in these hormones may be
  overcome by increase in prolactin

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The Breast A modified apocrine gland
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The Breast

• Estrogens stimulate growth of the ductal system
• Progesterone stimulates development of
  lobuloalveolar system
• Once developed, the breast no longer depends on
  steroid hormones

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Puberty
Lactation
1st Pregnancy
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The Breast

• Asymmetrical growth at puberty is common
• Exact equivalence in breast size is usually never
  attained
• Changes in size, shape and contour are
  correctable by surgery, not hormone therapy
• Size has no bearing on function

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Prolactin

• Secreted by lactotropes in anterior pituitary
• Lactotropes found in lateral wings of pituitary
• Shares high degree of similarity with growth
  hormone

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Prolactin

• Regulated by hypothalamic releasing factors and
  inhibiting factors
• Major regulatory influence is inhibitory
• Dopamine is principle prolactin inhibiting factor
• TRF is a prolactin releasing factor

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Prolactin Neuroendocrine Regulation
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Neuroregulation of Prolactin

• Major regulatory influence is inhibitory
• GABA and DA are neuroactive inhibitors
• DA is most profound inhibitor of prolactin

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Prolactin Control Dopamine Agonists and
Antagonists
Metoclopramide DA antagonist
L-DOPA CB154 DA agonists
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Prolactin Control Influence of Estrogen
Ethinyl Estradiol (BCPs)
Lactotrope
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Prolactin Secretion

• Increased secretion in response to sleep and food
  intake
• Increased secretion in response to stress,
  exercise, orgasm
• Sleep entrained 24 hour rhythm
• Peak levels at night

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Prolactin Secretion 24-hour Rhythm
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Inappropriate Prolactin Secretion

• Hypothalamic hyperprolactinemia
• Pituitary hyperprolactinemia
• Drugs (dopamine antagonists)
• Thyroid dysfunction
• Chronic renal failure

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Breast Changes During Pregnancy
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Prolactin and Pregnancy

• Prolactin levels rise 10-20 fold during pregnancy
• Prolactin is produced by pituitary and uterine
  decidua
• Although prolactin stimulates breast growth and
  differentiation during pregnancy, lactation does
  not occur

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The Breast and Pregnancy

• Rapid growth and branching of ductules occurs at
  the beginning of first pregnancy
• True alveoli are not present until the third
  month of first pregnancy
• Nipples increase in size, areola may become more
  pigmented

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Onset of Lactation

• Full lactation is inhibited by high levels of
  estrogen and progesterone
• Progesterone antagonizes the action of prolactin
  on prolactin receptor and reduces prolactin
  binding
• The signal for lactogenesis is the rapid
  disappearance of estrogen and progesterone
  post-partum

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Post-partum

• All placental hormones rapidly decline after
  delivery
• Estradiol and progesterone decline sharply
• Within 24 hours have almost reached normal
  pre-pregnancy levels

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Lactation

• Breast engorgement and lactation begin 3-4 days
  post-partum
• Initial fluid released after delivery is called
  colostrum and is not true breast milk
• Prolactin levels gradually decline, but remain
  elevated throughout interval of breastfeeding
• Suckling elicits sharp increments in prolactin
  necessary for continued milk production

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Pregnancy Weeks
Post-partum days
Post-partum months
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Lactation

• Dependent on anterior and posterior pituitary
  function
• Prolactin sustains secretion of milk
• Oxytocin contracts myoepithelial cells to empty
  alveoli

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Posterior Pituitary Hormones Oxytocin
Vasopressin
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Milk Letdown Reflex

• Ejection of milk NOT the result of mechanical
  suction
• Afferent neurons, stimulated during suckling,
  stimulate oxytocin release
• Often milk is released at times when baby is not
  suckling (infants cry, emotional stress) through
  centrally mediated oxytocin release

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Milk Let-down Reflex
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Babys Feeding

• Duct system empties into 15-20 different areolar
  apertures in nipple
• In response to appropriate stimuli, milk fill the
  lactiferous sinuses beneath the areola
• Compression of these sinuses results in
  expression of milk (babies suckling)

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• No woman should be discouraged from
  breast-feeding
• No correlation between pre-pregnancy breast size
  and milk production
• Timing of first feeding may influence success

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Breastfeeding

• Psychologically, there is no substitute for human
  breast milk
• Bonding established at suckling improves
  mother-infant interactions measurable 2 years
  later
• Compassion and understanding are also essential
  towards the woman who chooses not to breastfeed

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Breastfeeding

• Nutritionally, there is no substitute for human
  breast milk
• Modified cows milk formulas are not absorbed as
  easily
• Modified cows milk formulas are compositionally
  different

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Breastfeeding

• Immunologically, there is no substitute for human
  breast milk
• IgA antibodies found in breast colostrum and
  breast milk protect neonatal GI tract
• IgG antibodies found in breast milk provide
  short-term humoral immunity

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Prevention of Lactation

• Maintenance of high levels of estrogen or
  progesterone post-partum will prevent lactation
• Drugs (dopamine agonists) that decrease prolactin
  secretion prevent or inhibit established
  lactation
• Tight breast binders diminish engorgement in the
  immediate post-partum period

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Lactational Amenorrhea

• Protection against rapid re-conception
• Natures birth control
• Unreliable contraception by todays standards
• Mediated through high levels of prolactin

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Lactational Amenorrhea

• GnRH, FSH, LH secretion inhibited by high levels
  of prolactin
• Prolactin works through DA/?-endorphin system to
  inhibit GnRH release
• Same mechanism in prolactin-secreting pituitary
  adenomas that result in hyperprolactinemia

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Pulsatile LH Changes During Lactation
Pre-pregnancy
Lactating