Document Detail

The Role of Glucocorticoids in Pregnancy, Parturition, Lactation, and Nurturing in Melanocortin Receptor 2-Deficient Mice.
MedLine Citation:
PMID:  21303938     Owner:  NLM     Status:  Publisher    
Maternal glucocorticoids are critical for fetal development, but overexpression can be deleterious. Previously we established a mouse line deficient in melanocortin receptor 2 (MC2R). MC2R(-/-) mice have undetectable levels of corticosterone despite high levels of ACTH and defects resembling those in patients with familial glucocorticoid deficiency. Here we analyzed the role of glucocorticoids in pregnancy, parturition, lactation, and nurturing in MC2R(-/-) mice. MC2R(-/-) mice were fertile and produced normal litters when crossed with MC2R(+/+) mice. However, MC2R(-/-) females crossed with MC2R(-/-) males had no live births, and approximately 20 of the embryos at d 18.5 of pregnancy were of normal body size but were dead when born. MC2R(-/-) pregnant females crossed with MC2R(+/+) males had detectable serum corticosterone levels, suggesting the transplacental passage of corticosterone from fetus to mother. MC2R(+/-) pups delivered from MC2R(-/-) females crossed with MC2R(+/+) males mice thrived poorly with MC2R(-/-) mothers but grew to adulthood when transferred to foster mothers after birth, suggesting that MC2R(-/-) females are poor mothers or cannot nurse. MC2R(-/-) females had normal alveoli, but penetration of mammary epithelium into fat pads and expression of milk proteins were reduced. Myoepithelial cells, which force milk out of the alveoli, were fully developed and differentiated. Pup retrieval behavior was normal in MC2R(-/-) mice. Exogenous corticosterone rescued expression of milk proteins in MC2R(-/-) mothers, and the pups of treated mothers grew to adulthood. Our results reveal the importance of glucocorticoids for fetal survival late in pregnancy, mammary gland development, and milk protein gene expression.
Dai Chida; Keiko Miyoshi; Tsuyoshi Sato; Tetsuya Yoda; Takefumi Kikusui; Yoichiro Iwakura
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-2-8
Journal Detail:
Title:  Endocrinology     Volume:  -     ISSN:  1945-7170     ISO Abbreviation:  -     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-2-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Immunology and Pathology (D.C.), Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan; Division of Molecular Pathogenesis (D.C., Y.I.), Center for Experimental Medicine and Systems Biology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan; Department of Molecular Biology (K.M.), Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima 770-8504, Japan; Department of Oral and Maxillofacial Surgery (T.S., T.Y.), Saitama Medical University, Saitama Medical University, Saitama 350-0495, Japan; and Department of Companion Animal Research (T.K.), Azabu University, Kanagawa 229-8501, Japan.
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