Mammary cell activity and turnover in dairy cows treated with the prolactin-release inhibitor quinagolide and milked once daily

Abstract

To assess the regulation of mammary cell activity, survival, and proliferation by prolactin (PRL), 5 Holstein cows in early lactation received daily i.m. injections of 1mg of quinagolide, a suppressor of PRL release, for 9 wk, whereas 4 control cows received the vehicle (water) only. During the last week of treatment, one udder half was milked once a day (1×) and the other twice a day (2×). Mammary biopsies were harvested 1 wk before and 4 and 8 wk after the start of quinagolide treatment. The quinagolide injections reduced milk yield and resulted in lower levels of κ-casein and α-lactalbumin mRNA in the mammary biopsies at wk 4 compared with the control cows. In the mammary tissue of the quinagolide-treated cows at wk 8 of treatment, cell proliferation (as determined by proliferating cell nuclear antigen labeling) was lower and apoptosis (as determined by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay) was higher than in the mammary tissue of the control cows. During differential milking, mammary epithelial cells (MEC) were extracted from the milk by centrifugation and purified by immunocytochemical binding to allow variations in the levels of mammary transcripts to be observed. After 9 wk of treatment, levels of α-lactalbumin and κ-casein mRNA were lower in the MEC isolated from milk of the quinagolide-treated cows. This effect was associated with lower PRL receptor mRNA levels and a tendency toward lower viability in the milk-isolated MEC from the 2×-milked glands. The decrease from 2× milking to 1× milking also downregulated α-lactalbumin and κ-casein transcripts in the milk-isolated MEC. Viability was higher for the MEC collected from the 1×-milked udder halves compared with the 2×-milked halves. In conclusion, the reduction in milk yield after chronic administration of the PRL-release inhibitor quinagolide is associated with a reduction in mammary cell activity, survival, and proliferation in lactating dairy cows. Reduced milking frequency was also associated with a decrease in MEC activity.

Unilateral once daily milking locally induces differential gene expression in both mammary tissue and milk epithelial cells revealing mammary remodeling

“…These results suggest that milk-purified MEC may be representative of mammary tissue MEC, in which transcription of genes controlling cell proliferation is downregulated when milk production is decreased. However, a significant downregulation of LALBA transcripts in milk-purified MEC, which was consistent with previous studies in cows (10,12) and goats (4, 5), was observed in mammary tissue only with the less stringent FDR microarray analyses. The analyses of milk-purified MEC may prevent any interference between the quantification of MEC gene expression and that of other cell types (myoepithelial cells, endothelial cells, and adipocytes) present in the biopsies.…”

“…Nevertheless, the inhibition/activation of PRL release in cows have similar cellular targets. Indeed, the inhibition of milking-induced PRL release, already described in dairy cows (30), can also modify cell turnover and cell activity (12). Moreover, transcriptome analyses performed on mouse mammary glands and HC11 cells after PRL treatments revealed that a certain number of modulated genes are similar to those described in our study [SCL34A2, ALDO3, CTSC, SLC35A2, ERRB2, SQLE, CEBPD, SCD, ANGPT14 (37)].…”

“…The analyses of milk-purified MEC may prevent any interference between the quantification of MEC gene expression and that of other cell types (myoepithelial cells, endothelial cells, and adipocytes) present in the biopsies. Such interferences have recently been observed in dairy cows, where the effects of inhibiting milking-induced PRL release were more significant in milk-purified MEC than in mammary biopsies (12). By contrast, biopsy sampling enabled the performance of other analyses (e.g., immunohistological) that were useful to further characterize mammary cell remodeling during unilateral ODM in cows.…”

Effects of polyunsaturated fatty acids from plant oils and algae on milk fat yield and composition are associated with mammary lipogenic and SREBF1 gene expression

“…However, we did not observe any modification of Bax mRNA abundance neither in milk purified MEC nor in mammary tissue (data not shown). A better indicator of changes in cell proliferation and apoptosis would have been immunohistochemical analyses (Boutinaud et al, 2012), but mammary tissue sections could not be prepared in the current study. In our study, linseed oil plus algae increased the loss of MEC in the milk, but the differences were not significant (49% higher than SAT and 48% higher than SUNA).…”

Inhibiting prolactin by cabergoline accelerates mammary gland remodeling during the early dry period in dairy cows

“…The cessation of milking, however, also is induced by changes in systemic factors such as the galactopoietic hormones that are released at milking. Milking-induced prolactin (PRL) release, for example, was demonstrated to have a role in regulating MEC activity and turnover (Boutinaud et al, 2012;Lollivier et al, 2015). The inhibition of PRL by quinagolide, a dopamine agonist, was shown to hasten bovine mammary involution (Ollier et al, 2013).…”