ZBTB20 Regulates Prolactin Expression and Lactotrope Function in Adult Mice

Abstract Lactotropes are prolactin (PRL)-secreting endocrine cells in the anterior pituitary. We have established the zinc finger protein ZBTB20 as an essential transcription factor for lactotrope specification, the disruption of which results in complete loss of lactotropes in mice. However, the potential role of ZBTB20 in mature lactotropes remains unclear. Here we demonstrate that ZBTB20 acts as a critical cell-autonomous regulator for PRL expression in mature lactotropes in adult mice. Via a CRISPR/Cas9 approach, we first generated a tamoxifen-inducible Prl-CreER knockin mouse line that could efficiently mediate gene recombination specifically in lactotropes. Conditional deletion of the Zbtb20 gene specifically in mature lactotropes at adulthood led to a substantial decrease in PRL levels both in the pituitary and in plasma, without significant alterations of lactotrope relative density in the pituitary from male or female mice. Furthermore, conditional disruption of Zbtb20 in adult female mice did not significantly change pregnancy-elicited lactotrope expansion, but caused an impaired mammary gland expansion and lactation due to the PRL defect. Thus, our data point to an important role of ZBTB20 in regulating PRL expression and lactotrope function at adulthood.