Topic 96 - Mammary gland development, lactogenesis

Question 1

Words to include

Answer 1

• Milk
  
  • Nutrition
  • Protection against pathogens
    
    • Colostrum
      
      • Maternal immunity
      • Nutritive role
      • Laxative effect

Anatomy

• Lobus glandularis mammariae
• Lobulus gladularis mammariae
• Acinus mammariae
• Ductuli lactiferi
• Sinus lactiferi
  
  • Pars glandularis
  • Pars papillaris sinus lactiferi
• Muscle layer
• Rosette - Fürstenberg
• Ductus papillaris
• Sphincter

Phases of mammary gland development

• Mammogenesis
  
  • Development of mammary gland
• Lactogenesis
  
  • Milk synthesis
  • Milk secretion
• Galactopoesis
  
  • Maintainance of milk production
• Ejection
  
  • Milk let down
• Involution
  
  • Regressive transformation of the gland
• Mammogenesis
• Lactogenesis-1
• Lactogenesis-2
• Calving
• Galactopoesis
• Pregnancy
• Drying up
• Mammary gland
• Dry period

Mammogenesis

• Development before birth
  
  • Endocrionlogical mechanisms during early embryonic life
  • Androgens (testosterone) inhibits in male fetus
• Development from birth to pregnancy (puberty)
  
  • Stages:
    
    • ​Isometric growth
    • Allometric growth
    • Isometric growth
  • Development due to stimulation of:
    
    • ​Estrogens
    • Progesterone
    • Growth hormone
    • Glucocorticoids
• Development during pregnancy
  
  • Lobulo-alveolar development due to endocrinological effects:
    
    • PRL
    • Glucocorticoids
    • Placenta lactogen
    • Local factors
• Development during lactation
  
  • Alveo/lobular growth until peak lactation
  • Mammary epithelial cells begin to secrete
  • Lactation:
    
    • Continous growth until peak-lactation
    • Milk production related to number of:
      
      • Secretory cells
      • Secretory activity
    • Dying cells > growing cells
  • Dry period:
    
    • Secretory cells degenerate

Hormonal effects in mammogenesis

• Growth hormone
  
  • Development of parenchyma
  • Expression of epithelial receptors
• Glucocorticoids
  
  • Development of ducts
  • Growth of lobulo-alveolar structure
• Estrogen
  
  • Stimulates development of parenchyma
  • IGF: transmitter of effect
• Progesterone
  
  • Stimulating lobulo-alveolar development
• Prolactin
  
  • Ru: permissive effect on steroids
• Placenta lactogen
  
  • GH-like effect
  • PRL-like effect
  • Influences size of calf
• Local factors
  
  • IGF is necessary for E2 & GH
    
    • Mammary gland development
• Development of alveoli:
  
  • Estrogen
  • GH
  • Coricosteroids
• Development of duct system:
  
  • PRL
  • Progesterone

Lactogenesis

• Mammary epithelial cells are converted from non-secretory state → secretory state
• Stage 1:
  
  • Cytological and enzymatic differentiation of alveolar epithelial cells
  • Formation of colostrum
  • P4 & E2 inhibit real milk production
  • Chemical and morphological changes
• Stage 2:
  
  • Intensive secretion of milk
  • Changes:
    
    • ​Cardiovascular
    • Metabolic
    • Secretory

Hormonal effects in lactogensis

• Progesterone
  
  • Antilactogenic
    
    • Inhibits synthesis of:
      
      • α-lactalbumin
      • Casein
    • Ability of prolactin to induce protein synthesis ↓
    • Synergism between prolactin and glucocorticoids ↓
• Prolactin
  
  • ​Lactogenic
  • Milk protein syntheis ↑
• Glucocorticoids
  
  • ​Lactogenic hormones
  • Induce differentiation of:
    
    • Rough endoplasmic reticulum
    • Golgi apparatus
  • Differentiation important for prolactin induced protein synthesis
• Estrogen
  
  • ​Indirect lactogenic
  • Secretion of PRL and other lactogeinc hormones from pituitary gland ↑
  • PRL-receptors in mammary cells ↑
  • Stimulation of synthesis of:
    
    • Caseil
    • α-lactalbumin
• Local factors in lactogenesis
  
  • PGF_2α
    
    • _​Produced by uterus and mammary gland
    • Inhibits milk secretion
      
      • ​Inactivated/eliminated at parurition
• Suckling
  
  • Stimulates secretion of lactogen
• Lactose in lactogenesis
  
  • Syntheis of α-lactoalbumin initiated by:
    
    • P4 ↓
    • Glucocorticoids & PRL ↑

Galactopoesis

• Maintainance of lactation
• Regulation:
  
  • Galactopoietic hormones
  • Local mammary factors
    
    • Milk removal

Hormonal factors

• Hormonal complex maintains galactopoesis:
  
  • Prolactin
  • Growth hormones
  • Thyroid hormones
  • Glucocorticoids
• Local factors
  
  • Nursing/milking triggers release of galactopoietic hormoens
  • Ø milk removal → ø stimulation for prolactin
    
    • Intra-mammary pressure
      
      • ​Acute accumulation of milk in gland
    • Sympathetic nerves activated due to increased pressure → decrease mammary blood flow
    • Feedback Inhibitor of Lactation (FIL)
      
      • Ø milk removal → FIL in alveolar lumen → ø synthesis and secretion of milk

Milk ejection

• Two-component neuro-hormonal reflex
  
  • ​Neural afferent - CNS - hormonal effect
  • Neural component = afferent component
  • Hormonal component = efferent component
• Transfer of milk from lobulo-alveolar space → ducts
  
  • Due to contraction of myoepithelial cells

Oxytocin

• Released without mechanical stimulation of udder
• Additional sensory stimuli: Visual, auditory and olfactory
  
  • Oxytocin secretion from neurohypophysis

Question 2

Topics to include in the essay

Answer 2

1. Mammary gland development (mammogenesis)
   
   • Stages:
     
     • Development before birth
     • Development from birth to pregnancy (puberty)
     • Development during pregnancy
     • Development during lactation
   • Hormonal effects in mammogonesis
2. Lactogenesis
   
   • Stages
   • Hormonal effects in lactogenesis
3. Galactopoesis
   
   • Regulation
   • Hormonal factors
4. Milk ejection

Question 3

Name and define the phases of mammary gland development

Answer 3

• Mammogenesis: The development of the mammary gland
• Lactogenesis: The milk synthesis and milk secretion
• Galactopoesis: The maintenance of milk production
• Ejection: Milk let down
• Involution: Regressive transformation of the gland

Question 4

Mammogenesis

Answer 4

• Mammogenesis: development of the mammary gland

4 stages of mammogenesis:

1. ​Developement before birth
   
   • ​​Influenced by endocrinological mechanisms during early embryonic phase
   • Androgens (eg. testosterone) inhibit the process in male fetuses
2. ​Developement from birth to pregnancy (puberty)
   
   • ​Stages
     
     1. Isometric growth
     2. Allometric growth
     3. Isometric growth
   • During puberty, development of mammary ducts takes place due to stimulation of:
     
     • Estrogens
     • Progesterone
     • Gowth hormone
     • Glucocorticoid
3. ​Developement during pregnancy
   
   • ​​​​Further lobulo-alveolar development happens due to endocrinological effects:
     
     • PRL
     • Glucocorticoids
     • Placenta lactogen
     • Local factors​
4. ​Developement during lactation
   
   • ​​Further alveo/lobular growth until peak lactation, the regression
   • Mammary epithelial cells begin to secrete
   • During lactation:
     
     • ​Continous growth until peak lactation
     • Dying cells > growing cells
   • During dry period:
     
     • ​Secretory cells degenerate to prepare for the next lactation

Question 5

Hormonal effects in mammogenesis

Answer 5

• ​Growth hormone
  
  • ​Development of parenchyma
  • Expession of epithelial receptors
• Glucocorticoids
  
  • ​Important in:
    
    • Development of ducts
    • Growth of lobulo-alveolar structure
• Estrogen
  
  • ​Stimulate development of parenchyma
  • IGF is important as a transmitter of effect
• Progesterone
  
  • ​Stimulating lobulo-alveolar development
• Prolactin
  
  • ​Ru: premissive effect on steroids
• Placenta lactogen
  
  • ​GH-like effect
  • PRL-like effect
  • Influences size of calf
• Local factors
  
  • _​_IGF is necessary for E2 and GH
    
    • ​To influence mammary gland development
• Development of alveoli:
  
  • ​Estrogen
  • GH
  • Corticosteroids
• Development of duct system:
  
  • ​PRL
  • Progesterone

Question 6

Lactogenesis

Answer 6

• Lactogenesis:
  
  • ​Milk synthesis and milk secretion
  • Mammary epithelial cells are converted from a non-secretory state to a secretory stat
• End of ​pregnancy to time of parturirion

Two stages:

1. ​Stage 1
   
   • Cytological and enzymatic differentiation of alveolar epithelial cells
   • Specific milk components (eg. fat droplets and proteins) make their first appearance in the mammary gland
   • Formation of colostrum (and immunological uptake)
     
     • P4 + E2 inhibit the real milk porduction in stage 1
   • Gradual chemical and morphological changes
2. Stage 2
   
   • _​_Copious secretion of all milk components
   • Copious milk secretion begins when:
     
     • Inhibitory effect of P4 on lactogenesis ↓
     • Prolactin ↑
   • Changes:
     
     • Cardiovascular
     • Metabolic
     • Secretory
   • Glucocorticoids ↑

Question 7

Hormonal effects in lactogenesis

Answer 7

• Progesterone
  
  • _​_Antilactogenic
• Prolactin
  
  • _​_Lactogenic
  • Milk protein synthesis ↑
• Glucocorticoids
  
  • _​_Lactogenic
• Estrogen
  
  • _​_Indirect lactogenic
  • Increases secretion of PRL and other hormones from the pituitary gland
  • Increase the number of PRL-receptors in mammary cells
  • Stimulates secretion of:
    
    • Casein
    • α-lactalbumin
• Local factors in lactogeneis
  
  • ​PGF_2α
    
    • ​Inhibits milk secretion

Question 8

Colostrum

1. In which phase is colostrum produced
2. Role of colostrum

Answer 8

1. Colostrum is produced in lactogenesis, stage 2
2. ​Role:
   
   • ​Maternal immunity
     
     • ​Immunoglobulins are transmitted from mother to fetus (passive immunity)
   • Nutritive role
     
     • ​More proteins, lipids and minerals compared to milke (ø eq)
     • Also present: water, fat soluble vitamins and essential amino acids
   • Laxative effect
     
     • ​Mucous components in colostrum help to remove the meconium (embryonal faeces)

Question 9

Galactopoesis

Answer 9

• Galactopoesis: Maintainance of milk production
• Regulated by:
  • Galctopoetic hormones
  • Local mammary factors
    
    • ​Milk removal

Question 10

Hormonal factors of galactopoesis

Answer 10

• The hormonal complex which maintains the galactopoesis:
  
  • Prolactin (most important, ø ru: GH)
  • Growth horomne
  • Thyroid hormones
  • Glucocorticoids

​​​

• Local factors
  
  • ​If milk removal is not maintained there is no stimulation for prolactin release
    
    • Acute accumulation of milk in the gland cause an increase in intra-mammary pressure
    • This pressure activates sympathetic nerves in the gland → decrease mammary blood flow → availability of hormones and nutrients to the gland is reduced

Question 11

Milk ejection

Answer 11

• Milk ejection: Transfer of milk from lobulo-alveolar space into the ducts
• Two-component neuro-hormonal reflex:
  • ​Neural afferent - CNS - hormonal efferent
  • Neural component = afferent component
  • Hormonal component = efferent component

Oxytocin

• Oxytocin can be released without mechanically stimulating the udder
  
  • Additional sensory stimuli: visual, auditory & olfactory → oxytocin secretion from neurohypophysis ↑