Thread by @astuebe

Last talk of the day: Prolactin: Pleiotropic actions in pregnancy and lactation #ABM2022

Prolactin's role:
- Required for milk production
- Acts on secretory epithelial cells to promote synthesis of milk proteins
- Mammary gland development during pregnancy #ABM2022

Prolactin secretion outside of lactation:
- Dopamine inhibits prolactin secretion
- Prolactin stimulates dopamine release
- Low basal prolactin levels, with some variation in menstrual cycle
#ABM2022

Prolactin levels rise during pregnancy... #ABM2022 pubmed.ncbi.nlm.nih.gov/31843563/

What's the mechanism for reduced dopamine secretion during pregnancy & lactation? #ABM2022

Hypothesis: is gene transcription & protein translation altered? #ABM2022

Implication of animal study: during pregnancy, TIDA neurons secrete enkephalin instead of dopamine... #ABM2022 cell.com/cell-reports/f…

Feedback is not lost, but rather changed in the
maternal brain... #ABM2022

Knockout mouse model -> deleted prolactin receptors from brain... without prolactin receptor, neuron phenotypic change doesn't happen pubmed.ncbi.nlm.nih.gov/30759390/ ncbi.nlm.nih.gov/pmc/articles/P… #ABM2022

Trangenic mouse model -> slower weight gain - finding persists even when KO mother feeds wild-type pups #ABM2022

What happens for a feeding session? PRL knock-out -> reduced weight gain from 90 to 270 minutes - and removal of pups doesn't affect PRL levels as would be expected #AM2022

Working hypothesis: chronic prolactin / HPL activation during pregnancy is needed to "set up" prolactin secretion & lactation after birth #ABM2022

Implications for breastfeeding medicine: might maternal obesity be affecting breastfeeding via placental lactogen? pubmed.ncbi.nlm.nih.gov/29763375/ #ABM2022

The prolactin receptor is widely expressed in the mouse - what else is it doing? #ABM2022 pubmed.ncbi.nlm.nih.gov/31373638/

Disruption of prolactin -> GDM phenotype in mouse model... also relevant for nursing behavior, food intake, and supressing voluntary physical activity in pregnancy... #ABM2022 pubmed.ncbi.nlm.nih.gov/35131854/

Such a great talk! I wish I had the patience to do basic science! #ABM2022

Knockout animals have chronically high prolactin - w/o the appropriate changes needed to drive supply and demand - they produce milk, but not in a supply & demand way... #ABM2022

Working hypothesis: some prolactin receptor pathways are "turned off" in pregnancy... perhaps this one? #ABM2022

So many questions! Why do reglan / domperidone work if dopamine is down-regulated in pregnancy/lactation? What might enkephalin have to do w/ DMER? How do partial opiate antagonists affect enkephalin?