Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Normal development of the mammary gland is fundamental for lactation and requires exquisite cellular coordination. The gap junction proteins Cx26, Cx32 and Cx30 have been reported in luminal epithelial cells of the mammary gland while Cx43 is expressed in myoepithelial cells and in the stroma. This project aimed to determine the role of Cx43 in mammary gland development and function by employing a mouse model (Gja1(Jrt/+)) that harbors an autosomal dominant Cx43 mutation, and wild-type (WT) littermates. The highly phosphorylated species of Cx43, the total gap junction plaque number and gap junctional intercellular communication were reduced in mammary glands from Gja1(Jrt/+) mice, resulting in delayed development of the ducts. At parturition, Cx43 levels and gap junction plaque numbers were still reduced in Gja1(Jrt/+) mice, yet the morphology of the gland did not differ from WT mice. Interestingly, while higher than WT levels of beta-casein and WAP were present in the gland of Gja1(Jrt/+) mice, oxytocin failed to stimulate milk delivery to the ducts. Together, these data revealed that decreased levels of Cx43 result in delayed development of the mammary gland and a full complement of Cx43 is necessary for the expulsion of milk.
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PMID:Decreased levels of connexin43 result in impaired development of the mammary gland in a mouse model of oculodentodigital dysplasia. 1845 14

Intercellular communication is essential for glandular functions and tissue homeostasis. Gap junctions couple cells homotypically and heterotypically and co-ordinate reciprocal responses between the different cell types. Connexins (Cxs) are the main mammalian gap junction proteins, and the distribution of some Cx subtypes in the heterotypic gap junctions is not symmetrical; in the murine mammary gland, Cx26, Cx30 and Cx32 are expressed only in the luminal epithelial cells and Cx43 is expressed only in myoepithelial cells. Expression of all four Cxs peaks during late pregnancy and throughout lactation suggesting essential roles for these proteins in the functional secretory activity of the gland. Transgenic (Tg) mice over-expressing Cx26 driven by keratin 5 promoter had an unexpected mammary phenotype: the mothers were unable to feed their pups to weaning age leading to litter starvation and demise in early to mid-lactation. The mammary gland of K5-Cx26 female mice developed normally and produced normal levels of milk protein, suggesting a defect in delivery rather than milk production. Because the mammary gland of K5-Cx26 mothers contained excessive milk, we hypothesized that the defect may be in an inability to eject the milk. Using ex vivo three-dimensional mammary organoid cultures, we showed that tissues isolated from wild-type FVB females contracted upon treatment with oxytocin, whereas, organoids from Tg mice failed to do so. Unexpectedly, we found that ectopic expression of Cx26 in myoepithelial cells altered the expression of endogenous Cx43 resulting in impaired gap junction communication, demonstrated by defective dye coupling in mammary epithelial cells of Tg mice. Inhibition of gap junction communication or knock-down of Cx43 in organoids from wild-type mice impaired contraction in response to oxytocin, recapitulating the observations from the mammary glands of Tg mice. We conclude that Cx26 acts as a trans-dominant negative for Cx43 function in myoepithelial cells, highlighting the importance of cell type-specific expression of Cxs for optimal contractile function of the mammary myoepithelium.
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PMID:Asymmetric expression of connexins between luminal epithelial- and myoepithelial- cells is essential for contractile function of the mammary gland. 2550 Jun 15