DNA synthesis by ovine mammary alveolar epithelial cells: effects of heparin, epidermal growth factor-related peptides and interaction with stage of pregnancy

Forsyth, Isabel A.; Taylor, J. Andrew; Moorby, C D

doi:10.1677/joe.0.1560283

Cited by 6 publications

(9 citation statements)

References 31 publications

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“…This may be a direct effect of IGF-I or of synergistic actions with other growth factors. A synergistic interaction between IGF-I and transforming growth factor-(TGF-) has been suggested by Forsyth et al (1998), and significant expression of TGF-mRNA in the bovine mammary gland (Plath et al 1997) supports this notion.…”

Section: Discussionmentioning

confidence: 99%

The expression of the IGF family and GH receptor in the bovine mammary gland

Plath-Gabler¹,

Gabler²,

Sinowatz³

et al. 2001

Journal of Endocrinology

103

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To study the involvement of the IGFs in mammary development and lactation of the cow, the temporal expressions of IGF-I and -II, its receptor type 1 (IGFR-1), IGF-binding proteins (IGFBPs)-1 to -6 and GH receptor (GHR) mRNA were examined. This was carried out for different stages of mammogenesis, lactogenesis, galactopoiesis and involution in the bovine mammary gland of 26 animals. Furthermore, IGF-I was localised by immunohistochemistry. The highest mRNA concentrations for IGF-I were detected in the mammary tissue of late pregnant heifers (days 255-272) and significantly lower expression was detected during lactogenesis and galactopoiesis. Immunohistochemistry of IGF-I revealed only a weak staining in the epithelium of the ducts during mammogenesis. The epithelium of the alveoli were negative during mammogenesis, lactogenesis and galactopoiesis but displayed distinct IGF-I activity during involution. In the stroma a distinct staining of the cytoplasm of adipocytes and of vascular smooth muscle cells was observed. A certain percentage of fibroblasts (usually 20-30%) were also immunopositive. In contrast, highest expression for IGFR-1 was detected during galactopoiesis and involution. The lowest mRNA concentration for IGFR-1 was found during pregnancy (days 194-213). In general, the expression of IGF-II was not regulated during mammogenesis and lactation, but decreased during involution. The mRNA for the six binding proteins was detected in the bovine mammary gland. The dominant binding proteins were IGFBP-3 and -5. The highest expression of IGFBP-3 was observed during mid-pregnancy and the lowest during late lactation, involution and in nonpregnant heifers. The mRNA for IGFBP-5 increased during late mammogenesis and lactogenesis followed by a decrease thereafter. In general, the mRNA concentrations for IGFBP-2 , -4 and -6 were barely detectable during all stages. In contrast, the expression for IGFBP-1 was upregulated in the mammary gland of virgin heifers and increased around the onset of lactation. mRNA for GHR was found during all stages examined without outstanding fluctuations.In conclusion, locally produced IGF-I and -II may mediate mammogenesis. The high mammary IGFR-1 mRNA during lactation suggests a role for peripheral IGF-I in maintenance of lactation. The role of IGFBPs in the mammary gland needs further evaluation.

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Section: Discussionmentioning

confidence: 99%

The expression of the IGF family and GH receptor in the bovine mammary gland

Plath-Gabler¹,

Gabler²,

Sinowatz³

et al. 2001

Journal of Endocrinology

103

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“…Development of the mammary gland is probably influenced by multiple growth factors and their synergistic or antagonistic interactions (Oka et al 1991, Forsyth et al 1998. Many of these growth factors originate in the mammary gland and may act in an autocrine, juxtacrine or paracrine manner.…”

Section: Discussionmentioning

confidence: 99%

Contribution of insulin-like growth factor (IGF)-I and IGF-binding protein-3 to mitogenic activity in bovine mammary extracts and serum

Ms¹,

Purup²,

Vestergaard³

et al. 1999

Journal of Endocrinology

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Peripubertal development of the mammary gland is probably mediated by locally produced growth factors acting in concert with circulating mitogens. Our objective was to investigate the effect of recombinant human insulin-like growth factor-binding protein-3 (rhIGFBP-3) or insulin-like growth factor-I (IGF-I) antibodies on the IGF-I-related mitogenic activity of bovine serum and of mammary tissue extracts in primary mammary epithelial cell cultures. Cells were obtained from prepubertal female calf mammary tissue and cultured in three-dimensional collagen gels. An aqueous mammary parenchymal tissue extract (pooled from 20 prepubertal heifers) or serum (pooled from 3 heifers) at a concentration of 5% was added to the medium containing either rhIGFBP-3 or monoclonal or polyclonal antibodies to human IGF-I. Cell proliferation was evaluated using [methyl-3 H]thymidine incorporation as a measure of DNA synthesis. Addition of mammary extracts stimulated DNA synthesis 545% compared with basal medium. Addition of serum stimulated DNA synthesis by 28%. Mitogenic activity of serum and added IGF-I was abolished by addition of rhIGFBP-3 in equimolar concentrations with IGF-I. For mammary extracts, mitogenic activity was inhibited by 35%, 50%, and 82% by the addition of rhIGFBP-3 at, respectively, 1, 2 and 4 times the molar IGF-I concentration in the extract. Addition of rhIGFBP-3 to basal medium reduced DNA synthesis by 26%, whereas IGF-I antibodies had no consistent effect. These results indicate that circulating and mammary-synthesized IGF-I and IGFBPs probably play a critical role in prepubertal development of the bovine mammary gland.

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“…Synthesis of DNA was increased about 3.5 and 1.75 fold over basal medium by EGF and TGF-α at a concentration of 50 ng/ml. The previous studies with alveolar cells from pregnant sheep 25 also showed significant effects of both EGF and TGF-α but the effect of EGF was smaller and not clearly dose-related compared with TGF-α. Likewise, Collier et al 9 found that bovine mammary epithelial cells from pregnant heifers responded more to bovine TGF-α than to EGF.…”

Section: The Epidermal Growth Factor (Egf) Familymentioning

confidence: 75%

“…EGF and TGF-α both stimulated DNA synthesis in mammary tissue explants from midpregnant heifers 23 , in mammary epithelial cells from pregnant heifers and cows 9,24 and in alveolar cells prepared from pregnant sheep 25 . DNA synthesis was also stimulated by EGF in undifferentiated mammary epithelial cells from 4-6 mo old heifers 7 , by TGF-α in alveolar cells from non-pregnant, pregnant and lactating sheep 16 , and by amphiregulin in alveolar cells prepared from pregnant sheep 25 . Furthermore, EGF infused into the bovine mammary gland, caused an increase in DNA synthesis in the gland 26 .…”

Section: The Epidermal Growth Factor (Egf) Familymentioning

confidence: 94%

Involvement of Growth Factors in the Regulation of Pubertal Mammary Growth in Cattle

Purup¹,

Vestergaard²,

Sejrsen³

Biology of the Mammary Gland

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Pubertal mammary growth in heifers is dependent on interactions of many hormones and growth factors of which some are stimulatory while others are inhibitory. Although estrogen and growth hormone (GH) are of primary importance, more recent studies have suggested a role for both systemic and mammary tissue-specific growth factors. Growth factors may act as mediators of estrogen and GH or through specific effects of their own. These growth factors include insulin (INS), IGFs (IGF-I and IGF-II), epidermal growth factor (EGF), FGFs (FGF-1 and FGF-2), TGFs (TGF-alpha and TGF-beta's, amphiregulin (AR), platelets derived growth factor (PDGF), and mammary derived growth factor-1 (MDGF-1). Using mammary epithelial cells derived from prepubertal heifers and cultured in three-dimensional collagen gels as an in vitro model, we have investigated the mitogenic effects of a number of different growth factors (IGF-I, des(1-3) IGF-I, IGF-II, INS, EGF, TGF-alpha, AR, FGF-1, FGF-2, and TGF-beta 1). As expected, IGF-I, des(1-3)IGF-I, IGF-II and INS all stimulated proliferation of mammary cells with des(1-3)IGF-I being the most potent and INS the least potent. The mitogenic effect of IGF-I could be inhibited by both IGFBP-2 and IGFBP-3 showing that these binding proteins modulate the bioactivity of IGF-I in the mammary gland at the cellular level. Regulation of IGF availability by IGFBPs in the extracellular environment therefore is critical for IGF action in the mammary gland. Proliferation of mammary epithelial cells was also stimulated by growth factors of the EGF family, i.e. EGF, TGF-alpha and AR, however, not as much as growth factors from the IGF family. Members of the fibroblast growth factor family showed various mitogenic activities. FGF-1 stimulated DNA synthesis while FGF-2 in concentrations above 10 ng/ml inhibited DNA synthesis. TGF-beta 1 at very low concentrations stimulated proliferation slightly whereas higher concentrations strongly inhibited proliferation of mammary epithelial cells and inhibited mitogenesis induced by growth factors of both the EGF- and IGF family. This shows that TGF-beta 1 is a very potent regulator of pubertal mammary growth.

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DNA synthesis by ovine mammary alveolar epithelial cells: effects of heparin, epidermal growth factor-related peptides and interaction with stage of pregnancy

Cited by 6 publications

References 31 publications

The expression of the IGF family and GH receptor in the bovine mammary gland

The expression of the IGF family and GH receptor in the bovine mammary gland

Contribution of insulin-like growth factor (IGF)-I and IGF-binding protein-3 to mitogenic activity in bovine mammary extracts and serum

Involvement of Growth Factors in the Regulation of Pubertal Mammary Growth in Cattle

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