Lactation Flashcards
What are the effects of OT on the lactating alveolus?
OT binds to receptors on the myoepithelial cells and causes them to contract, pushing the milk out of the nipple
What are the effects of PRL on the lactating alveolus?
PRL acts on the epithelial cells and causes production of the constituents of milk.
What 2 hormones are involved in the growth of ducts at puberty?
estrogens and progesterone. They also require PRL, GH, IGF-1, and cortisol
What hormones are required by the pre-lactating mammary cell to get it ready for milk secretion?
prolactin, estrogen and progesterone, insulin, cortisol and GH.
What are the effects of progesterone and estrogen during pregnancy?
The high levels of P and E characteristic during pregnancy overall prevent the synthesis and secretion of milk proteins. However, E also stimulates PRL production in the pituitary by causing the lactotrphe cells to proliferate. But overall, doesn’t allow for milk production and secretion during pregnancy
What is the effect of prolactin on the lactating cell?
Causes the synthesis of milk constituents as well as maintaining the growth and differentiation of the mammary gland so that it can continue to produce milk
What family do the PRL receptors bind to?
PRL is similar to GH receptor and belongs to the cytokine receptor super family.
What are the effects of progesterone on the expression of the PRL receptor?
Progesterone inhibits expression of the PRL receptor in the breast
What are the effects of estrogen and progesterone on milk production?
interfere with synthesis of milk proteins
How does PRL interact with its receptor?
PRL binds to receptor which dimerizes and interacts with JAK (a tyrosine kinase). JAK phosphorylates STAT5a which then can dimerize and translocate into the nucleus to change transcription. STAT5a is a transcription factor.
How does cortisol and estrogen receptor affect the actions of STAT5a?
- cortisol enhances STAT5a
2. ER suppresses STAT5a
How does progesterone affect the actions of cortisol on STAT5a?
cortisol usually enhances STAT5a, but progesterone suppresses the effects of cortisol and thus doesn’t allow STAT5a to be enhanced
What proteins does STAT5a have an affect on?
casein
How and where is casein made and what is its role?
Casein is made in the RER and in the golgi, phosphate groups are added by casein-kinase. These negatively charged phosphates allow casein to complex calcium. The casein-Ca complexes aggregate into micelles and this is what creates the curds in milk.
How is lactose made in the body?
Glucose gets converted to UDP-galactose. In the golgi the galactose can combine with lipids and proteins by the actions of the galactosyl transferase.
What allows galactosyl transferase to bind glucose?
PRL causes synthesis of alpha lactalbumin which complexes with galactosyl transferase so that it now has a Km that allows it to bind glucose and add it to galactose, making lactose
What are the 2 ways that the lipids of milk can be generated?
- chylomicrons are taken up into epithelial cells where they are then degraded to glycerol and FA, then eventually reform TG
- Can be made de novo from glucose, this step requires INSULIN
What are the 5 different ways that milk constituents can be secreted into the alveolus of the mammary gland?
- membrane route (K, Na, Cl, H2O)
- Golgi Route (casein, lactose, Ca)
- Milk fat route
- Transcytosis (transcellular, IgA)
- Paracelleular route (leukocytes, ions when no tight junctions)
What molecules are released via milk protein secretion?
casein, alpha lactalbumin, lactose, all are packaged into secretory vesicles and released by exocytosis.
How are Na, K, and Cl transported into milk via membrane route?
- ICF membrane has NaK pump that maintains low Na ICF and high K ICF.
- on the luminal membrane there are epithelial Na and K channels that allow the Na and K to freely permeate
- Cl in the lumen is less than Cl in the ICF maybe due to Cl pump
How is calcium transported into milk?
complexed to casein or via CaATPase which pumps Calcium into vesicles against concentration gradient. Calcium gets trapped in the vesicles when it complexes with phosphates and citrate
Since women are loosing a lot of Calcium from their bones for milk production, how are calcium plasma and milk levels controlled?
The mammary glands secrete PTHrP which is not normally secreted in the blood. PTHrP binds to osteoblasts and activates them to express RANKL and make MCSF thus leading to activation of osteoclasts and leading to bone breakdown.
What is the birth control effect of PRL?
PRL inhibits release of GnRH thus leading to lower levels of FSH/LH and low estradiol. If low estradiol, then the granulosa cells will not proliferate and we will not get a LH spike for ovulation
When lactating, are regular PTH levels high or low?
low-PTHrP inhibits PTH because plasma Ca levels are increased thus the parathyroids are not activated
