Endocrine Abstracts

Increased mammary metabolism after child-birth supports the synthesis of milk components and is critical for initiating lactation during postpartum days 1-4. We utilised clinical and cellular approaches to investigate whether growth hormone (GH), which is reported to increase milk yield in breastfeeding women, may play a role in initiating lactation and promoting mammary metabolism. We recruited n=30 pregnant women (age range 24-41 years) following informed consent and measured serum GH at 36 weeks’ gestation and on postpartum day-4. All women had term births and initiated lactation by postpartum day-4. Serum GH significantly increased at the onset of lactation (0.5±0.1 mIU/l on postpartum day-4 vs. 0.2±0.02 mIU/l at 36 weeks’ gestation, P<0.05). We next assessed the effects of GH in cultured primary human mammary cells (HMECs). Recombinant human GH (rhGH) caused a dose-dependent increase in the phosphorylation of Akt, which is a key signalling protein required for initiating lactation. Thus, 50 ng/mL and 500 ng/ml rhGH caused ~1.5-fold and ~2-fold increases in Akt phosphorylation, respectively (P<0.05, n=4 experiments). Phosphorylated Akt also influences oxidative phosphorylation and glycolysis, and we assessed these processes by measuring extracellular O₂ and pH, respectively, in HMECs treated with rhGH. Administration of 50 ng/mL rhGH did not affect pH, but after 30min caused a significant increase in the rate of O₂ consumed by these cells (579±28 vs. 456±14 pmol O₂/min/10 ⁶ cells for control HMECs, P<0.01, n=4 experiments), consistent with an upregulation of oxidative phosphorylation. Reverse transcription-quantitative PCR (RT-qPCR) of HMECs treated with 50 ng/mL rhGH for 24hrs demonstrated a significant increase in the expression of the ATP5A1, ATP5C1 and ATP5F1 genes (P<0.05, n=4 experiments), which all encode subunits of the mitochondrial ATP synthase. In summary, these clinical and cellular studies highlight a pivotal role for GH in promoting mammary cellular metabolism at the onset of lactation.