Endocrine Abstracts

Lactation promotes infant development and confers long-term health benefits to mothers and infants. However, the endocrine and paracrine mechanisms mediating milk synthesis remain to be fully elucidated. Hormones such as prolactin and progesterone trigger the onset of lactation, whereas local mammary factors are considered to play a greater role in the maintenance of milk synthesis. We hypothesised that mammary epithelial cytokines are required for established lactation, and utilised in silico and ex vivo approaches to identify candidate paracrine factors. In silico expression analysis was performed using a publicly available mammary epithelial cell RNA-seq dataset obtained from age-matched virgin, pregnant, and lactating mice (n=2 mice per group). An analysis of >250 genes encoding paracrine factors demonstrated that 6 genes (Il15, Apln, Cxcl3, Egf, Pdgfd, and Nrg1) had a greater than 2-fold increase in expression in mammary epithelial cells from lactating mice compared to cells from pregnant or virgin mice. Of these genes, Il15 which encodes interleukin-15, showed the greatest increase in expression (>8-fold increase) during lactation. Moreover, interleukin-15, a cytokine with immune and metabolic roles, is reported to signal via the signal transducer and activator of transcription 5 (STAT5) protein, which is the major intracellular mediator of milk synthesis. We therefore validated expression of interleukin-15 ex vivo by quantitative reverse transcriptase-PCR (qRT-PCR) using mammary glands obtained from n=5 virgin mice, n=5 mice in early lactation (lactation day 1), and n=5 mice in established lactation (lactation day 7). This showed that mammary gland interleukin-15 expression was not significantly increased during early lactation, but markedly increased, by around 40-fold in mice during established lactation compared to virgin mice (P<0.001). In summary, these findings highlight a potential role for mammary-expressed interleukin-15 during lactation. Further studies are warranted to determine whether this cytokine promotes milk synthesis.