Introduction: Hormonal Regulation of Mammary Development and Milk Protein Gene Expression at the Whole Animal and Molecular Levels

Forsyth, Isabel A.; Neville, Margaret C.

doi:10.1007/s10911-009-9146-4

Cited by 9 publications

(7 citation statements)

References 27 publications

(24 reference statements)

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“…GTPases are known to be involved in secretion of milk fat gobule 34 . The insulin pathway is reported to be involved in initiation of lactogenesis and regulation of milk secretion in humans 35 . These pathways are important for maintaining the high rate of protein biosynthesis in the mammary gland.…”

Section: Discussionmentioning

confidence: 99%

Buffalo milk transcriptome: A comparative analysis of early, mid and late lactation

Arora

Sharma

et al. 2019

Sci Rep

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The expression of genes and their regulation during lactation in buffaloes remains less understood. To understand the interplay of various genes and pathways, the milk transcriptome from three lactation stages of Murrah buffalo was analyzed by RNA sequencing. The filtered reads were mapped to the Bubalus bubalis as well as Bos taurus reference assemblies. The average mapping rate to water buffalo and Btau 4.6 reference sequence, was 75.5% and 75.7% respectively. Highly expressed genes (RPKM > 3000), throughout lactation included CSN2, CSN1S1, CSN3, LALBA, SPP1 and TPT1. A total of 12833 transcripts were common across all the stages, while 271, 205 and 418 were unique to early, mid and late lactation respectively. Majority of the genes throughout lactation were linked to biological functions like protein metabolism, transport and immune response. A discernible shift from metabolism in early stage to metabolism and immune response in mid stage, and an increase in immune response functions in late lactation was observed. The results provide information of candidate genes and pathways involved in the different stages of lactation in buffalo. The study also identified 14 differentially expressed and highly connected genes across the three lactation stages, which can be used as candidates for future research.

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Section: Discussionmentioning

confidence: 99%

Buffalo milk transcriptome: A comparative analysis of early, mid and late lactation

Arora

Sharma

et al. 2019

Sci Rep

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“…We conclude that insulin fosters differentiation and may inhibit cell proliferation in the mammary gland of the midpregnant mouse. mammary development; acinar culture THE HORMONAL REGULATION OF mammary development and milk secretion has received extensive research attention in the last half-century (14), and the roles of the major sex steroid hormones, estrogen and progesterone (P4), as well as the lactogenic hormones prolactin (PRL) and hydrocortisone (HC) are quite well understood (26,28). Insulin is another story.…”

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confidence: 99%

The insulin receptor plays an important role in secretory differentiation in the mammary gland

Neville

Webb

Ramanathan

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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Insulin is known to be an important regulator of milk secretion in the lactating mammary gland. Here we examine the role of insulin signaling in mammary development in pregnancy using a mouse with a floxed insulin receptor (IR) crossed with a mouse expressing Cre specifically in the mammary gland. In the mammary glands of these IR fl/fl Cre ϩ mice, expression of IR is significantly diminished throughout development. Glands from these mice had 50% fewer alveoli at midpregnancy; casein and lipid droplets were diminished by 60 and 75%, respectively, indicating a role for IR both in alveolar development and differentiation. In an acinar preparation from mammary epithelial cells (MEC) isolated from pregnant mice, insulin stimulated lumen formation, mammary cell size, acinar size, acinar casein content, and the formation of lipid droplets with a Km of ϳ1.7 nM. IGF-I and IGF-II had no effect at concentrations below 50 nM, and a function blocking antibody to the IGF type 1 receptor did not alter the response to insulin. We conclude that insulin interacting with IR is essential for mammary differentiation during murine pregnancy. Using array analysis, we then examined the expression of genes up-or downregulated Ͼ1.5-fold in the IR fl/fl Cre ϩ MECs, finding significant downregulation of differentiation specific genes and upregulation of cell cycle and extracellular matrix genes. We conclude that insulin fosters differentiation and may inhibit cell proliferation in the mammary gland of the midpregnant mouse. mammary development; acinar culture THE HORMONAL REGULATION OF mammary development and milk secretion has received extensive research attention in the last half-century (14), and the roles of the major sex steroid hormones, estrogen and progesterone (P4), as well as the lactogenic hormones prolactin (PRL) and hydrocortisone (HC) are quite well understood (26,28). Insulin is another story. It is difficult to ablate the insulin-secreting pancreatic islets, or to increase plasma insulin, without seriously impairing the metabolism of the whole animal; for this reason, alternative approaches have been necessary to elucidate the role of insulin in mammary gland development. The same concern extends to the use of transgenic and knockout mice that have been used to great effect to study steroid hormones. Although genetically modified mice can be used for studying the insulin system, as we will see the experimental design is crucial if complicating systemic effects are to be avoided.Much early data demonstrated a role for insulin in maintenance of milk secretion in the lactating animal (1,3,15,18,19,22,25,33,35). The earliest studies showed that insulin stimulated lipid synthesis in mammary slices from lactating ruminants (13). However, in these experiments, effects on mammary epithelial and adipose tissues were not distinguished. Furthermore, in the dairy cow, raising insulin levels from 0.25 to 1.3 nM in the context of glucose clamp experiments had no effect on milk production (21), suggesting that the lactating gland of the ...

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“…The MEC transformation across pregnancy and lactation is a multipart process that is dictated by a diverse group of hormones and growth factors (25,65). At the time of parturition MEC have become specialized and acquired the necessary enzymatic activity, biosynthetic capability and ultrastructural attributes to synthesize milk for the neonate (26,54,55,73).…”

Section: Introductionmentioning

confidence: 99%

“…The mammary gland synthesizes over 90% of the polypeptides found in milk de novo, and the major limitation to peptide biosynthesis is the availability of its blood-procured building blocks, specifically amino acids (10,26,95). Casein and whey proteins are the two major types of proteins found in milk (84,95).…”

Section: Introductionmentioning

confidence: 99%

Profiling solute-carrier transporters in key metabolic tissues during the postpartum evolution of mammary epithelial cells from nonsecretory to secretory

Patel

Casey

Plaut

2019

Physiological Genomics

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Modifications in the abundance of solute-carrier (SLC) transcripts in tandem with adjustments in genes-associated with energy homeostasis during the postpartum transition of the mammary epithelial cells (MEC) from nonsecretory to secretory is pivotal for supporting milk synthesis. The goal of this study was to identify differentially expressed SLC genes across key metabolic tissues between late pregnancy and onset of lactation. Total RNA was isolated from the mammary, liver, and adipose tissues collected from rat dams on day 20 of pregnancy (P20) and day 1 of lactation (L1) and gene expression was measured with Rat 230 2.0 Affymetrix GeneChips. LIMMA was utilized to identify the differential gene expression patterns between P20 and L1 tissues. Transcripts engaged in conveying anions, cations, carboxylates, sugars, amino acids, metals, nucleosides, vitamins, and fatty acids were significantly increased ( P < 0.05) in MEC during the P20 to L1 shift. Downregulated ( P < 0.05) genes in the mammary during the physiological transition included GLUT8 and SLC45a3. In the liver, SLC genes encoding for anion, carbonyl, and nucleotide sugar transporters were upregulated ( P < 0.05) at L1. while genes facilitating transportation of anions and hexose were increased ( P < 0.05), from P20 to L1 in the adipose tissue. GLUT1 and GLUT4 in the liver, along with GLUT4 and SGLT2 in the adipose tissue, were repressed ( P < 0.05) at L1. Our results illustrate that MEC exhibit dynamic molecular plasticity during the nonsecretory to secretory transition and increase biosynthetic capacity through a coordinated tissue specific SLC transcriptome modification to facilitate substrate transfer.

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Introduction: Hormonal Regulation of Mammary Development and Milk Protein Gene Expression at the Whole Animal and Molecular Levels

Cited by 9 publications

References 27 publications

Buffalo milk transcriptome: A comparative analysis of early, mid and late lactation

Buffalo milk transcriptome: A comparative analysis of early, mid and late lactation

The insulin receptor plays an important role in secretory differentiation in the mammary gland

Profiling solute-carrier transporters in key metabolic tissues during the postpartum evolution of mammary epithelial cells from nonsecretory to secretory

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