lactation

major components of mammary glands

• lobule: functional unit (collection of alveoli)

• alveoli: sac lined by 3 cellular layers (alveolar, myoepithelial, and vascular)

• milk duct: connect lobules to nipple

mammogenesis

development of the mammary gland & its components

mammogenesis in fetal development

establish rudimentary structure; mammary gland inactive

mammogenesis during puberty & cycling

• development of alveoli

  • progesterone

  • TGFβ limits alveolar growth

• elongation and branching of ducts

  • estrogen

  • glucocortioids

  • GH/IGFs

mammogenesis during pregnancy

• dramatic development of alveoli

  • progesterone (CL & placenta)

  • estrogens

  • prolactin (maternal pituitary & placental lactogens)

• major drivers of alveolar development both produced by placenta

lactogenesis

initiation of lactation

what hormone inhibits milk synthesis?

• progesterone

  • decreases around parturition → decreased inhibition of milk synthesis

  • time milk production with arrival of newborn

how is lactogenesis initiated?

• initiation of milk synthesis regulated by the same hormonal changes that initiate parturition

  • increase in estrogen:progesterone ratio

    • estrogen has a (+) effect on prolactin levels

  • glucocorticoid, prolactin peak

  • decreased progesterone

how do glucocorticoids affect lactogenesis?

increase transcription of genes encoding milk proteins

how does prolactin affect lactogenesis?

promotes formation of tight junction between alveolus cells

why can dopamine cause failure to initiate lactation?

dopamine inhibits prolactin secretion

galactopoiesis

maintenance/continued lactation after parturition

which hormones are involved in galactopoeisis?

• glucocorticoids & prolactin: maintain milk synthesis

• thyroxine & prolactin: control nutrient partitioning (direct nutrients to mammary gland)

  • thyroxine & growth hormones (ruminants)

why is suckling important for galactopoeisis?

• suckling causes neuroendocrine release of ACTH, prolactin, TSH, GH

• empties mammary gland

  • if pressure builds up, alveolar cells stop milk synthesis

what are the 3 major components of milk?

• lactose (glucose + galactose)

• proteins

  • caseins: group of phosphoproteins

  • “whey” proteins: e.g. globulins

• triglycerides (main source of energy)

• substrates are provided by blood

why is the antibody content high in colostrum vs. non-colostrum?

colostrum is formed before peaks of glucocorticoids and prolactin (i.e. before their formation of tight junctions) → antibodies trapped in alveolar cells after tight junctions form

how does suckling cause milk letdown?

suckling leads to neuroendocrine release of oxytocin → oxytocin causes contraction of myoepithelial cells → milk letdown

what hormones regulate nutrient partitioning?

• calcium: prolactin + parathyroid hormone related peptide

• glucose, protein, and lipids: thyroxine + prolactin (most species)/growth hormone (ruminants)

  • bovine GH/bovine somatotropin (bGH/bST)

how does prolactin regulate nutrient partitioning?

increases intestinal calcium absorption

how does parathyroid hormone related peptide regulate nutrient partitioning?

mobilizes bone calcium and kidney absorption of calcium

how can bST/bGH be used to promote further nutrient partitioning?

• mechanism is undefined

• wait until cow is back in positive energy balance (~10 weeks post parturition/lactogenesis)

• supplemental bST/bGH can increase milk production 10-20% over entire lactation period

why is bST/bGH use controversial?

• efficacy

  • need enough feed for cow

• effects on cow’s heath:

  • stress, mastitis, increased use of antibiotics

• effects on human health

  • antibiotics in milk, changes in milk composition

• social issues

  • milk without bST and organic milk more popular

involution (regression) of mammary gland

• death of alveolar cells; loss of tight junctions, macrophage infiltration

• important for health of mammary gland

• essential for accumulation of colostrum for new offspring

why does involution (of mammary gland) occur?

as offspring grow, suckle less → less galactopoietic stimuli + milk accumulation in alveoli → involution (regression) of mammary gland

lactational anestrus

• period of time following parturition in which the female’s HPG axis remains inactive → no ovarian activity

• occurs before the resumption of estrus cycle

• even after female restarts cycle, usually not effective

  • silent heats

  • anovulatory cycles

what causes lactational anestrus?

• prolactin: inhibits cycling

• environmental factors

  • nutrition

  • photoperiod

  • social cues

  • stress

silent heat

• follicle develops but no behavioral estrus

• possibly due to priming effects of P4 in brain during pregnancy

anovulatory cycle

follicle develops but no ovulation → become cystic follicles

female reproductive tract repair

• uterine involution: recovery process of uterus to return to original size. contraction down and loss of damaged tissues

• endometrial repair: regeneration

• cervix repair and remodel

how does progesterone affect milk synthesis in dairy cattle?

• lactation in dairy cows is less affected by high progesterone → can lactate and be pregnant at same time

• in most species, progesterone inhibits milk production