Endocrine Abstracts

The onset of lactation occurs during postpartum days 1-4 and is associated with altered mammary metabolism leading to increased milk component synthesis. We hypothesised that increases in metabolic hormones or cytokines after childbirth may support these processes. To investigate this, we recruited n=12 pregnant women following informed consent and measured: prolactin; thyroid-stimulating hormone; insulin; cortisol; insulin-like growth factor-1; and interleukin-6 (IL-6) in serial blood samples obtained in pregnancy (36 weeks’ gestation) and during postpartum days 1-4. Of these circulating factors, only IL-6 showed a significant increase after childbirth (plasma IL-6 =61±34pg/mL on postpartum day 1 vs. 1.1±0.4pg/mL at 36 weeks’ gestation, P<0.01) with levels normalising by postpartum day 4. We assessed the metabolic effects of IL-6 in human mammary cells (HMECs). IL-6 administered as a 100ng/mL dose caused a >90-fold increase (P<0.0001, n=4) in the phosphorylation of signal transducer and activator of transcription-3 (STAT3), which is the major IL-6 signalling protein. Phosphorylated STAT3 influences oxidative phosphorylation and glycolysis, and we assessed these processes by measuring extracellular O₂ and pH, respectively. HMECs treated with 100ng/mL of IL-6 for ≤48hrs showed no alterations in extracellular O₂ compared to control cells. However, IL-6-treated HMECs showed a significant increase in the extracellular acidification rate (0.44±0.004 vs. 0.37±0.007mpH/min/10⁶ cells for control HMECs, P<0.001, n=4), consistent with increased glycolysis. IL-6 also influences mitochondrial function, and we evaluated this by incubating HMECs with tetramethylrhodamine methyl ester (TMRM), a fluorescent dye sequestered in active mitochondria. HMECs treated with 100ng/mL IL-6 for ≤8hrs showed a >20% decrease in TMRM fluorescence (P<0.01, n=4) consistent with reduced mitochondrial activity. In summary, these findings demonstrate that circulating concentrations of the IL-6 metabolic cytokine transiently increase at the onset of lactation. Moreover, IL-6 may promote mammary glycolysis, which is a pathway generating substrates for milk synthesis.