Prolactin expression in mammary epithelium is indispensable for lactational development but not for redirecting testicular cells to mammary cell fates

Authors

• SM Rosenfield
• CA Boulanger
• AL George
• GH Smith

Abstract

Prolactin (Prl) expression by the mouse mammary epithelium has been reported but its function in mammary gland development is unclear. Transplantation studies where mammary Prolactin knockout (PrlKO) tissue fragments were inserted in the epithelium deprived mammary fat pads of wild type (WT) athymic female mice that were made pregnant and maintained until parturition demonstrated that mammary epithelium-derived Prl expression is indispensable for complete lactational development of the mouse mammary gland. Immuno-staining of PrlKO mammary outgrowths cross-sections for Estrogen Receptor alpha (ER-α), Progesterone Receptor (PR), and Ets domain transcription factor 5 (Elf5) and the proliferation marker Ki67 identified the function of mammary epithelium-derived Prl as a regulator of steroid hormone sensing and luminal secretory cell expansion. Incomplete lobulo-alveolar and lactational development of PrlKO mammary epithelium was rescued by PrlWT mammary epithelial cells (MEC) in studies where PrlKO and PrlWT MEC where pre-mixed before being injected in epithelium-cleared mammary fat pads of athymic mice. Complete lactational development was rescued in PrlKO mammary outgrowths at parturition after pre-mixing PrlKO MEC with seminiferous tubule cells isolated from adult WT mice. The PrlKO MEC redirected testicular cells to undertake mammary epithelial cell fates. Accordingly, the redirected testicular cells gave rise to MEC progeny that express Prl and Elf5 in the mammary outgrowths during pregnancy and lactation. These studies demonstrate that autocrine/paracrine Prl expression in the mammary epithelium is indispensable for the expansion and differentiation of secretory mammary alveolar cells during lactational development and not to redirect testicular cells towards mammary epithelial cell fates.

Scientific Focus Area: Molecular Biology and Biochemistry

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