Use of a prolactin-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 (prolactin (PRL)-Cre/ROSA26-expression of yellow fluorescent protein (EYFP)) in which PRL promoter activity at any time resulted in permanent, stable, and highly specific EYFP. Triple immunochemistry for GH, PRL, and EYFP was used to quantify EYFP+ve, PRL-ve, and GH+ve cell populations during pregnancy and lactation, and for up to 3 weeks after weaning, and concurrent changes in cell size were estimated. At all stages, the EYFP reporter was expressed in 80% of the lactotrophs, but in 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 lactotroph/somatotroph ratio was seen during pregnancy and lactation, whether assessed by immunochemistry for the reporter or PRL: findings confirmed by PRL 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 with 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.
Castrique
Emma
E
Henry Wellcome Labs for Integrative Neuroscience and Endocrinology, University of Bristol, Dorothy Hodgkin Building, Bristol, UK.
Fernandez-Fuente
Marta
M
Le Tissier
Paul
P
Herman
Andy
A
Levy
Andy
A
D000818:Animals; D016923:Cell Death; D002454:Cell Differentiation; D054338:Cell Transdifferentiation; D005260:Female; D013006:Growth Hormone / Q000378:metabolism; D019426:Integrases / Q000235:genetics / Q000378:metabolism*; D007774:Lactation / Q000378:metabolism*; D052682:Lactotrophs / Q000166:cytology / Q000378:metabolism*; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D023421:Models, Animal; D010641:Phenotype; D011247:Pregnancy; D011388:Prolactin / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D022661:RNA, Untranslated; D052683:Somatotrophs / Q000166:cytology / Q000378:metabolism*; D014886:Weaning
C110853:Gt(ROSA)26Sor non-coding RNA, mouse; D008164:Luminescent Proteins; D011506:Proteins; D022661:RNA, Untranslated; D011388:Prolactin; D013006:Growth Hormone; C045073:Cre recombinase; D019426:Integrases