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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.

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Histological features of the mammary gland of FVB mice during pregnancy and lactation. Mammary glands were isolated from FVB mice on (a,b) day 6 (P6), (c,d) day 12 (P12), and (e,f) day 18 (P18) of pregnancy, and (g,h) day 2 (L2) and (i,j) day 9 (L9) of lactation, fixed in neutral-buffered formalin, sectioned and stained with hematoxylin and eosin. Scale bars in (a, c, e, g and i) represent 100 μm, while those in (b, d, f, h and j) represent 10 μm.
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Figure 1: Histological features of the mammary gland of FVB mice during pregnancy and lactation. Mammary glands were isolated from FVB mice on (a,b) day 6 (P6), (c,d) day 12 (P12), and (e,f) day 18 (P18) of pregnancy, and (g,h) day 2 (L2) and (i,j) day 9 (L9) of lactation, fixed in neutral-buffered formalin, sectioned and stained with hematoxylin and eosin. Scale bars in (a, c, e, g and i) represent 100 μm, while those in (b, d, f, h and j) represent 10 μm.

Mentions: Histological changes in mammary gland morphology in the mouse during pregnancy and lactation are shown in Figure 1. Initial changes observed during pregnancy include an increase in ductal branching and the formation of alveolar buds (Figure 1a); this phase of differentiation is characterized by the largest increase in DNA synthesis and cellular proliferation during pregnancy [23]. The latter half of pregnancy is characterized by the expansion of alveolar buds to form clusters of lobuloalveolar units, followed by the differentiation of these structures into pre-secretory structures. By day 12 of pregnancy there is a readily apparent increase in the size of the epithelial compartment compared to the adipose compartment (Figure 1c), and expansion of the epithelium continues until the epithelial compartment predominates by late pregnancy (Figure 1e). The luminal space is clearly evident by late pregnancy, filled with a proteinaceous substance whose identity is not clear but may represent milk proteins, glycoproteins such as Muc1, lactoferrin, and possibily immunoglobulins (Figure 1f). Large lipid droplets are also present in the cytoplasm of the alveolar epithelial cells and, to some extent, in the luminal space (Figure 1f). Following parturition, the secretory lobuloalveolar structures become more apparent as the luminal space expands, and the epithelial cell layer becomes more prominent against the adipocytes (Figure 1g). The large lipid droplets, which were present at day 18 of pregnancy, are not present, having been replaced by small lipid droplets at the apical surface of the epithelial cells (Figure 1h), and although the luminal space may contain proteinaceous material when it has not been lost during fixation and sectioning, it stains much more lightly than during late pregnancy (Figure 1i versus 1b). By day nine of lactation in the mouse, the mammary gland is producing copious amounts of milk. Examination of the histology of the mammary gland at this stage reveals prominent luminal structures and ducts; however, few adipocytes are visible at this time (Figure 1i). This change is thought to reflect delipidation of adipocytes rather than a decrease in their number [24].


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)

Histological features of the mammary gland of FVB mice during pregnancy and lactation. Mammary glands were isolated from FVB mice on (a,b) day 6 (P6), (c,d) day 12 (P12), and (e,f) day 18 (P18) of pregnancy, and (g,h) day 2 (L2) and (i,j) day 9 (L9) of lactation, fixed in neutral-buffered formalin, sectioned and stained with hematoxylin and eosin. Scale bars in (a, c, e, g and i) represent 100 μm, while those in (b, d, f, h and j) represent 10 μm.
© Copyright Policy
Related In: Results  -  Collection

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Figure 1: Histological features of the mammary gland of FVB mice during pregnancy and lactation. Mammary glands were isolated from FVB mice on (a,b) day 6 (P6), (c,d) day 12 (P12), and (e,f) day 18 (P18) of pregnancy, and (g,h) day 2 (L2) and (i,j) day 9 (L9) of lactation, fixed in neutral-buffered formalin, sectioned and stained with hematoxylin and eosin. Scale bars in (a, c, e, g and i) represent 100 μm, while those in (b, d, f, h and j) represent 10 μm.
Mentions: Histological changes in mammary gland morphology in the mouse during pregnancy and lactation are shown in Figure 1. Initial changes observed during pregnancy include an increase in ductal branching and the formation of alveolar buds (Figure 1a); this phase of differentiation is characterized by the largest increase in DNA synthesis and cellular proliferation during pregnancy [23]. The latter half of pregnancy is characterized by the expansion of alveolar buds to form clusters of lobuloalveolar units, followed by the differentiation of these structures into pre-secretory structures. By day 12 of pregnancy there is a readily apparent increase in the size of the epithelial compartment compared to the adipose compartment (Figure 1c), and expansion of the epithelium continues until the epithelial compartment predominates by late pregnancy (Figure 1e). The luminal space is clearly evident by late pregnancy, filled with a proteinaceous substance whose identity is not clear but may represent milk proteins, glycoproteins such as Muc1, lactoferrin, and possibily immunoglobulins (Figure 1f). Large lipid droplets are also present in the cytoplasm of the alveolar epithelial cells and, to some extent, in the luminal space (Figure 1f). Following parturition, the secretory lobuloalveolar structures become more apparent as the luminal space expands, and the epithelial cell layer becomes more prominent against the adipocytes (Figure 1g). The large lipid droplets, which were present at day 18 of pregnancy, are not present, having been replaced by small lipid droplets at the apical surface of the epithelial cells (Figure 1h), and although the luminal space may contain proteinaceous material when it has not been lost during fixation and sectioning, it stains much more lightly than during late pregnancy (Figure 1i versus 1b). By day nine of lactation in the mouse, the mammary gland is producing copious amounts of milk. Examination of the histology of the mammary gland at this stage reveals prominent luminal structures and ducts; however, few adipocytes are visible at this time (Figure 1i). This change is thought to reflect delipidation of adipocytes rather than a decrease in their number [24].

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