In vivo inhibition followed by exogenous supplementation demonstrates galactopoietic effects of prolactin on mammary tissue and milk production in dairy cows

Abstract

It has been previously shown that the long-term inhibition of milking-induced prolactin (PRL) release by quinagolide (QN), a dopamine agonist, reduces milk yield in dairy cows. To further demonstrate that PRL is galactopoietic in cows, we performed a short-term experiment that used PRL injections to restore the release of PRL at milking in QN-treated cows. Nine Holstein cows were assigned to treatments during three 5-d periods in a 3×3 Latin square design: 1) QN: twice-daily i.m. injections of 1mg of QN; 2) QN-PRL: twice-daily i.m. injections of 1mg of QN and twice-daily (at milking time) i.v. injections of PRL (2µg/kg body weight); and 3) control: twice-daily injections of the vehicles. Mammary epithelial cells (MEC) were purified from milk so that their viability could be assessed, and mammary biopsies were harvested for immunohistological analyses of cell proliferation using PCNA and STAT5 staining. In both milk-purified MEC and mammary tissue, the mRNA levels of milk proteins and BAX were determined using real-time reverse-transcription PCR. Daily QN injections reduced milking-induced PRL release. The area under the PRL curve was similar in the control and PRL injection treatments, but the shape was different. The QN treatment decreased milk, lactose, protein, and casein production. Injections of PRL did not restore milk yield but tended to increase milk protein yield. In mammary tissue, the percentage of STAT5-positive cells was reduced during QN but not during QN-PRL in comparison with the control treatment. The percentage of PCNA-positive cells was greater during QN-PRL injections than during the control or QN treatment and tended to be lower during QN than during the control treatment. In milk-purified MEC, κ-casein and α-lactalbumin mRNA levels were lower during QN than during the control treatment, but during QN-PRL, they were not different from the control treatment. In mammary tissue, the BAX mRNA level was lower during QN-PRL than during QN. The number of MEC exfoliated into milk was increased by QN injections but tended to be decreased by PRL injections. Injections of PRL also increased the viability of MEC harvested from milk. Although PRL injections at milking could not reverse the effect of QN treatment on milk production, their effects on cell survival and exfoliation and on gene expression suggest that the effect of QN treatment on the mammary gland is due to QN's inhibition of PRL secretion.

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

“…Collectively, these findings suggest that MEC become exfoliated when they lose contact with survival factors contained in the extracellular matrix as previously shown by others (Katz and Streuli, 2007). Thus, a single treatment with cabergoline can achieve similar effects on MMP2-mediated activities and MEC exfoliation as several treatments with quinagolide (Ollier et al, 2013;Lollivier et al, 2015).…”

“…In contrast, cabergoline treatment downregulated mRNA expression of genes involved in cell death (BAX and CAPN2) that are normally upregulated in mammary tissue following dry-off. These findings were unexpected because PRL is known to have a survival effect in mammary tissue (Boutinaud et al, 2012;Lollivier et al, 2015). Further research is needed to investigate if the effect of cabergoline on cell death could be due to sampling time or to more efficient removal of dead cells by enhanced milk SCC .…”

“…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).…”

Cabergoline inhibits prolactin secretion and accelerates involution in dairy cows after dry-off

“…The ability of dopamine agonists to inhibit PRL secretion is a factor in suppressing unwanted lactation in women and female dogs (de Groot et al, 1998). In cows, the inhibition of PRL secretion by the pituitary gland after daily injections of quinagolide, a dopamine agonist, was also shown to reduce milk yield during established lactation (Lacasse et al, 2011;Lollivier et al, 2015). This decrease in milk yield was associated with lower levels of milk protein mRNA, in conjunction with reduced mammary epithelial cell survival and proliferation (Boutinaud et al, 2012).…”

Prolactin-Responsive Circular RNA circHIPK3 Promotes Proliferation of Mammary Epithelial Cells from Dairy Cow

“…Chronic administration of the PRL-release inhibitor quinagolide can suppress cell proliferation and enhance apoptosis in the mammary tissue of lactating dairy cows [5], whereas PRL injections lead to a higher cell proliferation rate. Besides, treated with quinagolide injection can reduce the apoptosis of mammary epithelial cells in lactating dairy cows [6]. PRL acts to stimulate the proliferation of bovine mammary gland epithelial cells [7].…”