Endocrine Abstracts

CCN family member 3 (CCN3) is reported in mice to be an osteoanabolic peptide secreted by hypothalamic kisspeptin-expressing neurons, and protects the maternal skeleton from excess resorption during lactation. However, its role in breastfeeding women is unknown. We investigated whether maternal CCN3 concentrations increase after childbirth and are associated with: 1) changes in prolactin, which regulates kisspeptin-expressing neuronal activity; and 2) bone formation, measured using pro-collagen type 1 N-terminal pro-peptide (P1NP). This study included n = 30 healthy pregnant women intending to breastfeed and aged >18 years. Blood samples were obtained following informed consent at 36 weeks’ gestation (baseline), postpartum day 4 (start of lactation), and during postpartum days 14-28 (established lactation). Biochemical values were compared with n = 22 age-matched healthy female volunteers who were neither pregnant or lactating. Mean+/-SEM plasma CCN3 concentrations were significantly higher during pregnancy (12.0+/-1.2 ng/mL) compared with healthy volunteers (5.9+/-0.6 ng/mL, P < 0.001). However, CCN3 values decreased to 7.3+/-0.7 ng/mL by postpartum day 4 and then significantly increased to 13.0+/-1.0 ng/mL, P < 0.001) by postpartum days 14-28. Serum prolactin showed a significant increase from 36 weeks’ gestation (3897+/-292 mU/l) to postpartum day 4 (4984+/-279 mU/l, P < 0.05) and this rise significantly correlated with the postpartum increase in CCN3 (r = 0.45, P < 0.05). Plasma P1NP concentrations were significantly higher at postpartum days 14-28 (80+/-5.5 ng/mL) compared with healthy volunteers (50+/-2.6 ng/mL, P < 0.001). Moreover, plasma P1NP correlated with CCN3 during pregnancy (r = 0.71, P < 0.001) and at postpartum days 14-28 once lactation was established (r = 0.48, P < 0.01). In summary, maternal plasma CCN3 shows a biphasic longitudinal pattern with an increase during pregnancy, decreased concentrations following childbirth and subsequent postpartum increase once lactation is established. Furthermore, the significant associations with prolactin and P1NP indicate possible regulation by prolactin and highlight CCN3 as a potential novel osteoanabolic hormone in breastfeeding women.