Endocrine Abstracts

The onset of lactation, termed ‘secretory activation’, occurs within 96 hours after childbirth and is mediated by physiological hyperprolactinaemia, which stimulates the mammary prolactin receptor (PRLR) to induce milk synthesis. However, the precise serum prolactin concentration required and effect of maternal factors such as age, parity, body mass index (BMI) and type of delivery remain to be elucidated. Moreover, the contribution of different mammary PRLR isoforms, which include the full-length PRLR and several shorter isoforms, to secretory activation is unknown. We investigated this in n = 226 healthy breastfeeding women (mean age=35 years, range 24-46) recruited following informed consent at 36 weeks’ gestation and followed up during postpartum days 1-5. All participants initiated milk secretion by postpartum day 4. Serum was obtained for prolactin measurements and mammary RNA isolated from milk samples for PRLR isoform analysis. Our findings showed that mean±SEM serum prolactin increased from 4082±102 mU/l at 36 weeks’ gestation to 5113±183 mU/l on postpartum day 1 (P < 0.0001) with prolactin values peaking at 5359±169 on postpartum day 2 and decreasing thereafter. However, delivery involving the use of forceps, suction or emergency c-section, all of which may delay secretory activation, abrogated the rise in prolactin; whilst maternal age, parity and BMI were not associated with serum prolactin. In addition, RNA-sequencing conducted in n = 56 participants showed that the full-length isoform is the most abundant type of mammary PRLR with its expression >40-fold higher than other shorter isoforms. Furthermore, mammary full-length PRLR expression significantly increased by >8-fold during postpartum days 1-5 (P < 0.0001). In summary, this study demonstrates that secretory activation is associated with a significant peripartum increase in serum prolactin and marked increase in mammary full-length PRLR expression. Moreover, assisted deliveries and emergency c-section impaired the prolactin rise, which may explain why these factors cause delayed secretory activation.