scholarly journals The Role of Glucocorticoids in Pregnancy, Parturition, Lactation, and Nurturing in Melanocortin Receptor 2-Deficient Mice

Endocrinology ◽  
2011 ◽  
Vol 152 (4) ◽  
pp. 1652-1660 ◽  
Author(s):  
Dai Chida ◽  
Keiko Miyoshi ◽  
Tsuyoshi Sato ◽  
Tetsuya Yoda ◽  
Takefumi Kikusui ◽  
...  

Abstract 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.

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Pengbo Wang ◽  
Jian Wu ◽  
Amber Wood ◽  
Matthew Jones ◽  
Robert Pedley ◽  
...  

AbstractVinculin is an essential component of cell adhesion complexes, where it regulates the strength and stability of adhesions. Whilst the role of vinculin in cell motility is well established, it remains unclear how vinculin contributes to other aspects of tissue function. Here we examine the role of vinculin in mammary epithelial cell phenotype. In these cells, correct adhesion to the extracellular matrix is essential for both the formation of polarised secretory acini and for the transcription of tissue-specific milk protein genes. We show that vinculin, through its interaction with talin, controls milk protein gene expression. However, vinculin is not required for the formation of polarised acini. This work reveals new roles for vinculin that are central to cellular differentiation, and for the ability of cells to interpret their extracellular microenvironment.


1981 ◽  
Vol 194 (3) ◽  
pp. 999-1006 ◽  
Author(s):  
L J Burditt ◽  
D Parker ◽  
R K Craig ◽  
T Getova ◽  
P N Campbell

1. The expression of alpha-lactalbumin and casein genes was examined in guinea-pig mammary tissue taken from animals both pre- and post-partum. 2. Analysis of total RNA by RNA excess hybridization with sequence-specific complementary DNA probes demonstrated that alpha-lactalbumin mRNA was present late in pregnancy, and that maximum concentrations were present at parturition. Casein gene transcripts were absent late in pregnancy (62 days), but by parturition were present at concentrations identical to those found at all time points examined throughout lactation. 3. Studies using mammary explants in organ culture showed that tissue from pregnant animals, or animals at parturition, synthesized and secreted only alpha-lactalbumin. After parturition, at the onset of casein synthesis, differential rates of secretion of alpha-lactalbumin and the caseins were observed. 4. The results are discussed in terms of the multiple intracellular mechanisms involved in the regulation of milk protein gene expression in the guinea-pig mammary gland.


2001 ◽  
Vol 155 (4) ◽  
pp. 531-542 ◽  
Author(s):  
Keiko Miyoshi ◽  
Jonathan M. Shillingford ◽  
Gilbert H. Smith ◽  
Sandra L. Grimm ◽  
Kay-Uwe Wagner ◽  
...  

Functional development of mammary epithelium during pregnancy depends on prolactin signaling. However, the underlying molecular and cellular events are not fully understood. We examined the specific contributions of the prolactin receptor (PrlR) and the signal transducers and activators of transcription 5a and 5b (referred to as Stat5) in the formation and differentiation of mammary alveolar epithelium. PrlR- and Stat5-null mammary epithelia were transplanted into wild-type hosts, and pregnancy-mediated development was investigated at a histological and molecular level. Stat5-null mammary epithelium developed ducts but failed to form alveoli, and no milk protein gene expression was observed. In contrast, PrlR-null epithelium formed alveoli-like structures with small open lumina. Electron microscopy revealed undifferentiated features of organelles and a perturbation of cell–cell contacts in PrlR- and Stat5-null epithelia. Expression of NKCC1, an Na-K-Cl cotransporter characteristic for ductal epithelia, and ZO-1, a protein associated with tight junction, were maintained in the alveoli-like structures of PrlR- and Stat5-null epithelia. In contrast, the Na-Pi cotransporter Npt2b, and the gap junction component connexin 32, usually expressed in secretory epithelia, were undetectable in PrlR- and Stat5-null mice. These data demonstrate that signaling via the PrlR and Stat5 is critical for the proliferation and differentiation of mammary alveoli during pregnancy.


1983 ◽  
Vol 96 (5) ◽  
pp. 1435-1442 ◽  
Author(s):  
YML Suard ◽  
M Haeuptle ◽  
E Farinon ◽  
J Kraehenbuhl

We analyzed the synthesis of DNA, the rate of cell proliferation, and the expression of milk protein genes in mammary cells grown as primary cultures on or in collagen gels in chemically defined media. We assessed DNA synthesis and cell growth, measured by [(3) H]- thymidine incorporation into acid-insoluble material, DNA content, and cell counts, in a progesterone- and prolactin-containing medium. In some experiments, cultures were pulsed for 1 h with [(3)H]thymidine and dissociated into individual cells which were cytocentrifuged and processed for immunocytochemistry and autoradiography. We analyzed expression of milk protein genes at the transcriptional, translation and posttranslational levels in progesterone-depleted medium in the presence or absence of prolactin. We measured protein secretion by radioimmunoassays with antisera directed against caseins, α-lactalbumin and milk transferrin1. We determined protein synthesis by incorporating radio-labeled amino acids into acid-precipitable material and by immunoprecipitating biosynthetically labeled milk proteins. We assessed the accumulation of casein mRNA by hybridizing total cellular RNA extracted from cultured cells with (32)P-labeled casein cDNA probes. On attached collagen gels, the cells synthesized DNA and replicated until they became confluent. The overall protein synthetic activity was low, and no milk proteins were synthesized or secreted even in the presence of prolactin. The block in milk protein gene expression was not restricted to translational or posttranslational events but also included transcription, since no casein mRNA accumulated in these cells. On floating gels, protein synthesis was threefold higher than in cells from attached gels. Overall protein synthesis as well as casein and α-lactalbumin synthesis and secretion were prolactin-dependent with maximal stimulation at around 10(-9) M. A marked inhibition occurred at higher hormone concentrations. Casein mRNA accumulated in these cells, provided prolactin was present in the medium. In contrast, these cells did not synthesize DNA, nor did they replicate. In embedding gels, the rate of cell proliferation was exponential over 25 d with a doubling time of approximately 70 h. The overall protein synthesis increase was parallel in time with the increase in cell number. Caseins and α-lactalbumin (in contrast to transferrin) were synthesized only in the presence of prolactin. We observed the same hormone dependency as with cells growing on floating gels. The number of casein- and transferring-positive cells was measured after dissociating the cell cultures. At day 12, 60 percent of the total cells stored transferring in small cytoplasmic vesicles, whereas only 25 percent of the cells accumulated casein. Differences in the organization and in the shape of mammary cells depending on cell surface conditions suggest that the geometry of the cells, their interaction with extracellular matrix constituents, and cell-to-cell interactions play a role in the expression of two mammary functions: DNA synthesis and growth, as well as milk protein gene expression.


2015 ◽  
Vol 4 (3) ◽  
pp. 205 ◽  
Author(s):  
Shikha Saxena ◽  
KV Thimmaraju ◽  
PremC Srivastava ◽  
AyazK Mallick ◽  
Biswajit Das ◽  
...  

2019 ◽  
Vol 15 (3) ◽  
pp. 156-158
Author(s):  
Aditi Priyamvara ◽  
Amit K. Dey ◽  
Antara Bagchi ◽  
Raveena Kelkar ◽  
Rajaram Sharma

Background: It is known that hormonal imbalances during pregnancy make women more susceptible to dental problems. High levels of progesterone and estrogen during pregnancy, lead to an increased inflammatory response to dental plaque thus causing predisposing to gum diseases such as gingivitis. If untreated, gingivitis leads to chronic periodontitis which may manifest systemically in form of cardiovascular, endocrine or even respiratory disorders. Also, hyperacidity in the oral cavity due to gastric reflux and vomiting leads to decreased pH thus damaging the tooth enamel making the oral cavity more prone to tooth decay and tooth loss. Studies also show that periodontal disease can also lead to adverse pregnancy outcomes such as pre-term and low birth weight babies. Objectives: We sought to understand the role of oral health in pregnancy. Methods: We identified major articles of interest in the field of oral health in pregnancy and drafted a mini-symposium based on relevant information. Conclusion: Regular dental visits and cognizant efforts to sustain a healthy oral environment can help women in the prevention and treatment of dental issues during pregnancy. The paper highlights the common oral manifestations during pregnancy and their local and systemic impact on the body during pregnancy. Furthermore, it also emphasizes the importance of good oral health practices to counteract the oral complications and the significance of oral health awareness in pregnant women.


2011 ◽  
Vol 18 (5) ◽  
pp. 255-258 ◽  
Author(s):  
Maria Makrides
Keyword(s):  

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