Effect of exogenous bovine growth hormone and ovariectomy on prepubertal mammary growth, serum hormones and acute in-vitro proliferative response of mammary explants from Holstein heifers

Purup, Stig; Sejrsen, K.; Foldager, J.; Akers, R.M.

doi:10.1677/joe.0.1390019

Cited by 75 publications

(86 citation statements)

References 20 publications

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“…However, the reduction in circulating concentration of estradiol in response to ovariectomy in prepubertal heifers was only 0.1 pg/ml (Purup et al, 1993), which appears inadequate to elicit the dramatic reduction in parenchymal growth that was noted in that study. Moreover, literature shows that a daily dose of , 0.1 mg/kg body weight (BW) estradiol is required to elicit positive responses in mammary epithelial cell (MEC) proliferation (Woodward et al, 1993;Capuco et al, 2002;Meyer et al, 2006a).…”

Section: Introductioncontrasting

confidence: 54%

Effect of staged ovariectomy on measures of mammary growth and development in prepubertal dairy heifers

Velayudhan

Huderson

McGilliard

et al. 2012

Animal

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Previous studies in prepubertal heifers suggest that the magnitude of reduction in mammary parenchymal growth in response to ovariectomy varies with the age at which surgery is performed. We hypothesized that ovarian secretions are essential for initiating mammary development but not required to maintain allometric mammary growth in prepubertal dairy heifers. The objectives of this study were to determine the effect of staged ovariectomy during the prepubertal period on mammary growth and tissue composition and the expression of selected genes. Prepubertal Holstein heifers at 2, 3 or 4 months of age were randomly assigned to one of two treatments, ovariectomized (OVX; n 5 12) or sham operated (INT; n 5 12). Mammary parenchyma (PAR) and fat pad (MFP) were harvested 30 days after surgery. Proximate composition of PAR and MFP (DNA, protein and lipid) as well as expression of the selected estrogen-responsive genes stanniocalcin1 (STC1), tissue factor pathway inhibitor precursor (TFPI) and proliferating cell nuclear antigen (PCNA) were determined in PAR and MFP by quantitative real-time PCR. The relative amount of epithelium and proportion of epithelia cell nuclei expressing the proliferation marker Ki67 were determined by histological and immunohistochemical analyses, respectively. MFP mass was not impacted by treatment but was decreased with age as was lipid content and concentration (P < 0.01). The mass of mammary PAR was reduced in OVX and increased with age (P < 0.01). Parenchymal tissue tended to have less total DNA, protein and lipid in OVX heifers. Parenchymal tissue concentrations of protein and DNA were increased with age and there was an age 3 treatment interaction. Treatment had no effect on either the Ki67 labeling index or percent epithelial area. The relative abundances of STC1, TFPI and PCNA mRNA in PAR were reduced in OVX. We did not find a significant impact of ovariectomy on mRNA expression when surgery was performed at 2 months compared with surgery at 3 or 4 months of age. However, having nearly undetectable PAR in two heifers ovariectomized at the earliest period (2 months of age) suggests that early ovariectomy is especially detrimental to subsequent parenchymal development.

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Section: Introductioncontrasting

confidence: 54%

Effect of staged ovariectomy on measures of mammary growth and development in prepubertal dairy heifers

Velayudhan

Huderson

McGilliard

et al. 2012

Animal

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“…This observation is indicative of reduced circulating estrogen (Hipkin 1969). In a previous study, estrogen was significantly reduced in 6-month-old ovariectomized heifers (Purup et al 1993). The reduction was approximately 0·1 pg/ml (representing about a 50% decrease), thus raising the question of whether such a small reduction could be responsible for such large changes in mammary development.…”

Section: Discussionmentioning

confidence: 78%

“…Because we were focused on rapid tissue collection, total mammary weights were the only gross measurements made at the time of slaughter. However, we believe that the total weight of mammary gland and fat pad were representative of parenchymal development based on our visual observations of parenchymal tissue available for sampling at the time of slaughter and the data of Purup et al (1993) showing that ovariectomy reduced both parenchymal tissue weight and total gland weight.…”

Section: Experimental Design and Samplingmentioning

confidence: 84%

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Interactions between the ovary and the local IGF-I axis modulate mammary development in prepubertal heifers

Berry

Howard²,

Jobst³

et al. 2003

Journal of Endocrinology

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The objective was to determine the effects of ovariectomy and epithelial-stromal interactions on mammary development and local expression of IGF-I and IGF-binding protein (IGFBP) mRNA in prepubertal heifers. An epithelium-free ('cleared') fat pad (CFP) was prepared in two glands in each of 14 Holstein heifers, aged 1-3 months. Eight of the calves were also ovariectomized. Serum concentrations of GH, IGF-I and prolactin were not affected by ovariectomy. At 6 months of age, calves were killed to provide mammary samples of parenchyma, CFP and intact fat pad (MFP). Total mammary mass was reduced in ovariectomized calves (130 21 g vs 304 25 g; P<0·001), and in several cases parenchymal tissue was essentially absent. Uterus weight was also reduced by ovariectomy (14·5 3·8 g vs 30·4 4·5 g; P<0·05). In support of our hypothesis that local IGF-I mediates prepubertal mammary development, mRNA expression of IGF-I was lower in ovariectomized than in control calves (62·1 7·8 vs 91·6 7·8 arbitrary units; P<0·05). Specific binding of IGF-I to mammary parenchymal microsomes was also reduced by ovariectomy (377 142 vs 868 82 c.p.m.; P<0·01), suggesting decreased sensitivity to IGF-I. Expression of IGFBP-3 and IGFBP-5 mRNA were not influenced by ovariectomy. Expression of IGF-I, IGFBP-3 and IGFBP-5 mRNA did not differ between CFP and MFP, suggesting that expression of these factors was not influenced by interactions between stroma and developing epithelium. Overall, the data suggested that interactions between the ovary and the local IGF-I axis act to optimize the availability and effectiveness of IGF-I within the gland to stimulate mammary growth.

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“…As mentioned above, the choice of model is essential for the outcome when milk bioactives are tested in cell cultures. To illustrate this point, it has proved difficult to demonstrate a direct mitogenic effect of 17b-estradiol on cell lines of bovine mammary epithelial cells in vitro , although oestrogen overall is known to play an important role in the development of the bovine mammary gland (Purup et al, 1993b;Capuco et al, 2002). As seen in Figure 1, we showed mitogenic effects of very low concentrations of 17b-oestradiol (E2) in heifer mammary gland explants.…”

Section: Choosing An Appropriate Cell-based Modelmentioning

confidence: 99%

Cell-based models to test the effects of milk-derived bioactives

Purup

Nielsen²

2012

Animal

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The life science industries have a strong interest in screening for novel bioactives in complex mixtures like milk and dairy products. Food bioactives are not only important for public health in general, but also have potential therapeutic applications for the treatment of a number of diseases. To identify these novel bioactives, establishment of robust screening assays is essential. The use of in vitro cell-based models for screening and testing have the advantage that several concentrations of mixtures or specific compounds can be assayed at the same time in cells from specific tissues. Primary cell cultures from target organs or established cell lines can be used to identify the most sensitive cells. In addition, a large number of transfected cell lines with very specific sensitivities have been developed. Different endpoints inherent to basal or more sophisticated cellular functions can be investigated, such as cell viability, apoptosis, migration, intracellular signalling, regulation of gene expression, morphology and metabolic alterations. The gastrointestinal tract is an obvious target for bioactive molecules delivered through milk and dairy products, because it lies at the interface between dietary components in the lumen and the internal processes of the host. Identification of bioactive factors that affects proliferation or migration of epithelial cells may have potential applications in promoting gastrointestinal health in both humans and animals. The mammary gland is another target organ of considerable interest since it has been estimated that up to 50% of all newly diagnosed breast cancers may be related to dietary factors. A large number of gastrointestinal and mammary epithelial cell lines are commercially available, but in order to study some cellular functions, primary cultures of freshly isolated cells are often preferred, as established cell lines do not always express specialised properties in culture.

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Effect of exogenous bovine growth hormone and ovariectomy on prepubertal mammary growth, serum hormones and acute in-vitro proliferative response of mammary explants from Holstein heifers

Cited by 75 publications

References 20 publications

Effect of staged ovariectomy on measures of mammary growth and development in prepubertal dairy heifers

Effect of staged ovariectomy on measures of mammary growth and development in prepubertal dairy heifers

Interactions between the ovary and the local IGF-I axis modulate mammary development in prepubertal heifers

Cell-based models to test the effects of milk-derived bioactives

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