Limits...
Key stages in mammary gland development. Secretory activation in the mammary gland: it's not just about milk protein synthesis!

Anderson SM, Rudolph MC, McManaman JL, Neville MC - Breast Cancer Res. (2007)

Bottom Line: Much of the research to date on mammary epithelial differentiation has focused upon expression of milk protein genes, providing a somewhat distorted view of alveolar differentiation and secretory activation.While expression of milk protein genes increases during pregnancy and at secretory activation, the genes whose expression is more tightly regulated at this transition are those that regulate lipid biosynthesis.The sterol regulatory element binding protein (SREBP) family of transcription factors is recognized as regulating fatty acid and cholesterol biosynthesis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, University of Colorado Health Sciences Center, East 17th Avenue, Aurora, CO 80045, USA. Steve.Anderson@uchsc.edu

ABSTRACT
The transition from pregnancy to lactation is a critical event in the survival of the newborn since all the nutrient requirements of the infant are provided by milk. While milk contains numerous components, including proteins, that aid in maintaining the health of the infant, lactose and milk fat represent the critical energy providing elements of milk. Much of the research to date on mammary epithelial differentiation has focused upon expression of milk protein genes, providing a somewhat distorted view of alveolar differentiation and secretory activation. While expression of milk protein genes increases during pregnancy and at secretory activation, the genes whose expression is more tightly regulated at this transition are those that regulate lipid biosynthesis. The sterol regulatory element binding protein (SREBP) family of transcription factors is recognized as regulating fatty acid and cholesterol biosynthesis. We propose that SREBP1 is a critical regulator of secretory activation with regard to lipid biosynthesis, in a manner that responds to diet, and that the serine/threonine protein kinase Akt influences this process, resulting in a highly efficient lipid synthetic organ that is able to support the nutritional needs of the newborn.

Show MeSH
Summary of gene expression during pregnancy and lactation by functional class. Adipocyte specific genes decline throughout pregnancy and early lactation while milk protein genes as a class increase over the same time period. The expression of other classes is stable during pregnancy, possibly representing expression in both the adipose and epithelial compartment and increases two- to three-fold (fatty acid and cholesterol synthesis) or decreases about two-fold (fatty acid and protein degradation) at parturition. Adipocyte genes, red; β-oxidation genes, navy blue; proteosome genes, teal; milk protein genes, brown; fatty acid biosynthesis genes, light brown; cholesterol biosynthetic genes, pink.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC1851396&req=5

Figure 3: Summary of gene expression during pregnancy and lactation by functional class. Adipocyte specific genes decline throughout pregnancy and early lactation while milk protein genes as a class increase over the same time period. The expression of other classes is stable during pregnancy, possibly representing expression in both the adipose and epithelial compartment and increases two- to three-fold (fatty acid and cholesterol synthesis) or decreases about two-fold (fatty acid and protein degradation) at parturition. Adipocyte genes, red; β-oxidation genes, navy blue; proteosome genes, teal; milk protein genes, brown; fatty acid biosynthesis genes, light brown; cholesterol biosynthetic genes, pink.

Mentions: Microarray studies have allowed us to examine temporal changes in mammary gene expression during secretory differentiation and activation in some detail [33]. The results are summarized in Figure 3, which shows mean relative expression levels for a number of classes of proteins through pregnancy and lactation to involution. During pregnancy, adipocyte genes decline about seven-fold, representing dilution by the growing alveoli, with a two-fold drop at the onset of lactation as the alveoli expand further. The overall expression level of milk protein genes increases about fivefold during pregnancy, with a further three- to four-fold increase at parturition. However, these mean values hide a good deal of variation in individual genes within these groups, as discussed in the next section. The other categories shown in Figure 3 remain relatively constant during pregnancy, with a sharp increase (genes for fatty acid and cholesterol synthesis) or decrease (genes for fatty acid degradation and the proteasome) at secretory activation. Examination of numerous mouse models that exhibit lactation failure tends to suggest that, if secretory activation does not occur properly, the mammary gland rapidly undergoes involution [54].


Key stages in mammary gland development. Secretory activation in the mammary gland: it's not just about milk protein synthesis!

Anderson SM, Rudolph MC, McManaman JL, Neville MC - Breast Cancer Res. (2007)

Summary of gene expression during pregnancy and lactation by functional class. Adipocyte specific genes decline throughout pregnancy and early lactation while milk protein genes as a class increase over the same time period. The expression of other classes is stable during pregnancy, possibly representing expression in both the adipose and epithelial compartment and increases two- to three-fold (fatty acid and cholesterol synthesis) or decreases about two-fold (fatty acid and protein degradation) at parturition. Adipocyte genes, red; β-oxidation genes, navy blue; proteosome genes, teal; milk protein genes, brown; fatty acid biosynthesis genes, light brown; cholesterol biosynthetic genes, pink.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1851396&req=5

Figure 3: Summary of gene expression during pregnancy and lactation by functional class. Adipocyte specific genes decline throughout pregnancy and early lactation while milk protein genes as a class increase over the same time period. The expression of other classes is stable during pregnancy, possibly representing expression in both the adipose and epithelial compartment and increases two- to three-fold (fatty acid and cholesterol synthesis) or decreases about two-fold (fatty acid and protein degradation) at parturition. Adipocyte genes, red; β-oxidation genes, navy blue; proteosome genes, teal; milk protein genes, brown; fatty acid biosynthesis genes, light brown; cholesterol biosynthetic genes, pink.
Mentions: Microarray studies have allowed us to examine temporal changes in mammary gene expression during secretory differentiation and activation in some detail [33]. The results are summarized in Figure 3, which shows mean relative expression levels for a number of classes of proteins through pregnancy and lactation to involution. During pregnancy, adipocyte genes decline about seven-fold, representing dilution by the growing alveoli, with a two-fold drop at the onset of lactation as the alveoli expand further. The overall expression level of milk protein genes increases about fivefold during pregnancy, with a further three- to four-fold increase at parturition. However, these mean values hide a good deal of variation in individual genes within these groups, as discussed in the next section. The other categories shown in Figure 3 remain relatively constant during pregnancy, with a sharp increase (genes for fatty acid and cholesterol synthesis) or decrease (genes for fatty acid degradation and the proteasome) at secretory activation. Examination of numerous mouse models that exhibit lactation failure tends to suggest that, if secretory activation does not occur properly, the mammary gland rapidly undergoes involution [54].

Bottom Line: Much of the research to date on mammary epithelial differentiation has focused upon expression of milk protein genes, providing a somewhat distorted view of alveolar differentiation and secretory activation.While expression of milk protein genes increases during pregnancy and at secretory activation, the genes whose expression is more tightly regulated at this transition are those that regulate lipid biosynthesis.The sterol regulatory element binding protein (SREBP) family of transcription factors is recognized as regulating fatty acid and cholesterol biosynthesis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, University of Colorado Health Sciences Center, East 17th Avenue, Aurora, CO 80045, USA. Steve.Anderson@uchsc.edu

ABSTRACT
The transition from pregnancy to lactation is a critical event in the survival of the newborn since all the nutrient requirements of the infant are provided by milk. While milk contains numerous components, including proteins, that aid in maintaining the health of the infant, lactose and milk fat represent the critical energy providing elements of milk. Much of the research to date on mammary epithelial differentiation has focused upon expression of milk protein genes, providing a somewhat distorted view of alveolar differentiation and secretory activation. While expression of milk protein genes increases during pregnancy and at secretory activation, the genes whose expression is more tightly regulated at this transition are those that regulate lipid biosynthesis. The sterol regulatory element binding protein (SREBP) family of transcription factors is recognized as regulating fatty acid and cholesterol biosynthesis. We propose that SREBP1 is a critical regulator of secretory activation with regard to lipid biosynthesis, in a manner that responds to diet, and that the serine/threonine protein kinase Akt influences this process, resulting in a highly efficient lipid synthetic organ that is able to support the nutritional needs of the newborn.

Show MeSH