Prolactin regulation of insulin-like growth factor 2 gene expression in the adult mouse choroid plexus

Abstract

There is clear evidence for carrier-mediated transport of prolactin into the brain, and it has been widely assumed that prolactin receptors (PRLRs) in the choroid plexus (ChP) might mediate this transport. Using PRLR knockout mice, we recently showed that PRLRs in ChP are not required for prolactin transport into the brain. Hence, the function of PRLR in the ChP remains unknown. PRLR expression is increased in the ChP during lactation, suggesting a possible role in adaptive function of prolactin at this time. To gain insight into prolactin function in the ChP, we have utilized RNA sequencing and NanoString techniques to characterize transcriptional changes in response to differing levels of prolactin at diestrus, during pregnancy, and in lactation. We have observed opposing transcriptional effects of prolactin on the ChP in different physiologic states, being primarily inhibitory during diestrus but stimulatory in lactation. Insulin-like growth factor 2 (Igf2), a highly expressing transcript found in the ChP, showed a 6-fold increase at lactation that returned to baseline on suppression of prolactin levels. These results indicate that Igf2 may be an important downstream mediator of prolactin-induced signaling in the ChP.—Phillipps, H. R., Rand, C. J., Brown, R. S. E., Kokay, I. C., Stanton, J.-A., Grattan, D. R. Prolactin regulation of insulin-like growth factor 2 gene expression in the adult mouse choroid plexus. FASEB J. 33, 6115–6128 (2019). www.fasebj.org.