Use of a PRL-Cre/ROSA-YFP transgenic mouse provides no evidence for lactotroph transdifferentiation after weaning, or increase in lactotroph/somatotroph proportion in lactation

In rats a shift from somatotroph dominance to lactotroph dominance during pregnancy and lactation is well reported. Somatotroph to lactotroph transdifferentiation and increased lactotroph mitotic activity are believed to account for this and associated pituitary hypertrophy. A combination of cell death and transdifferentiation away from the lactotroph phenotype has been reported to restore non-pregnant pituitary proportions after weaning. To attempt to confirm that a similar process occurs in mice, we generated and used a transgenic reporter mouse model (PRL-Cre/ROSA26-EYFP) in which prolactin promoter activity at any time resulted in permanent, stable and highly specific expression of yellow fluorescent protein (EYFP). Triple immunochemistry for GH, prolactin and EYFP was used to quantify EYFP+ve, prolactin-ve, and GH+ve cell populations during pregnancy, lactation and for up to three weeks after weaning, and concurrent changes in cell size estimated. At all stages, the EYFP reporter was expressed in 80% of lactotrophs, but fewer than 1% of other pituitary cell types, indicating that transdifferentiation from those lactotrophs where reporter expression was activated is extremely rare. Contrary to expectations, no increase in the lactotrophs/somatotroph ratio was seen during pregnancy and lactation, whether assessed by immunochemistry for the reporter or prolactin: findings confirmed by prolactin immunochemistry in non-transgenic mice. Mammosomatotrophs were rarely encountered at the age group studied. Individual EYFP+ve cell volumes increased significantly by mid-lactation compared to virgin animals. This, in combination with a modest and non cell type-specific estrogen-induced increase in mitotic activity, could account for pregnancy-induced changes in overall pituitary size.