Endocrine Abstracts

The onset of lactation after childbirth is a key determinant of successful breastfeeding. Copious milk secretion occurs by postpartum day 4 and is mediated by a decline in serum progesterone and high serum prolactin. However, the threshold prolactin concentration required is unclear. It is also unknown if changes in mammary prolactin sensitivity contribute to the initiation of lactation. To investigate this, we recruited 52 healthy pregnant women aged 26-42 years following informed consent. Serum prolactin was measured before and 45min after a breastfeed on postpartum days 1-4. Mammary prolactin receptor gene (PRLR) expression, an index of prolactin sensitivity, was assessed by reverse transcriptase-quantitative PCR using lactating cell RNA isolated from breastmilk samples on postpartum days 1-7, and compared to RNA obtained from non-lactating mammary cells isolated from breast reduction tissue. All participants reported onset of copious milk secretion by postpartum day 4. The mean serum prolactin after childbirth was elevated at 5208 mU/l (range 1686-8400) compared to the normal pre-pregnancy range of <560 mU/l. All women had postpartum serum prolactin values >3-fold above the upper limit of the pre-pregnancy range. Serum prolactin concentrations did not significantly change during postpartum days 1-4 and showed no acute increase during a breastfeed. However, PRLR expression significantly increased by >90-fold in lactating cells isolated from breastmilk compared to non-lactating mammary cells (n =4 biological replicates, P<0.001). Furthermore, mammary PRLR expression positively correlated with postpartum duration during the first 7 days after childbirth (R²=0.9, P=0.001). In summary, this study demonstrates that lactation onset after childbirth is associated with threshold prolactin concentrations >3-fold above the pre-pregnant normal range and is characterised by a marked increase in mammary PRLR expression during the early postpartum period. These findings highlight the importance of high serum prolactin combined with an acute rise in mammary PRLR for initiating human lactation.