Effects of inhibiting prolactin production with cabergoline on the physiology of the cow-dry period

Abstract Text:

Cabergoline is an ergot derivative with a high affinity for the D2 dopamine receptor whose dopaminergic effects cause inhibition of prolactin (PRL) secretion, and has been recently released as a dry-off facilitator (Velactis®, Ceva, France). A deep study of its effects along the dry period can help to understand the physiology of the mammary involution. Twenty-four Holstein cows (6 primiparous and 18 multiparous) were distributed in 2 treatments: i.m. injection of either 5 ml providing 5.6 mg of cabergolin (CAB) or 5 ml of saline solution (CTR) at the moment of dry-off.  Mammary gland biopsies of posterior quarters and tail blood samples were taken at -10, 9, and 23 d relative to dry-off and -9 and 21 d relative to calving to evaluate the effects of PRL inhibition on hormonal and tissue involution markers along the dry period and onset of the subsequent lactation.  Blood concentrations of insulin, PRL, IGF1, IGFBP5, GH, and progesterone were determined using immunoassays. Expression of genes coding for p16, ki67, igf, igfbp5, upa, mmp9, prlr, occludin, and caspase 3 was determined by qPRC. Lastly, immunohistochemical detection of Ki67, SIRT1 and P16 was performed and quantified by light microscopy. As expected, cows on CAB tended (P = 0.07) to have lower serum PLR concentrations (23.5±0.29 ng/mL) than cows on CTRL (36.4±0.25 ng/mL), and had a lesser (P < 0.001) expression of PRL receptor (prlr) in the mammary tissue (2.09±0.455 vs 1.77±0.423 relative expression units, respectively). Cabergolin increased (P < 0.05) blood insulin concentration (14.3±1.28 µU/mL) compared with CTR (10.7±1.14 µU/mL), but blood concentration of the remaining hormones were not affected although decreased (P < 0.05) as the dry period progressed. The expression of igf1 in the mammary gland increased (P < 0.05) in CAB cows in the dry period and decreased at the beginning of next lactation. Also, CAB cows had greater (P < 0.05) expression of mmp9 and occludin, which indicates a greater tissue involution and remodeling (P < 0.05). Also, immunohistochemical analyses showed an increase (P < 0.05) in sirt1 (a gene related with cell proliferation and insulin sensitivity) in CAB animals (75.9±12.02 relative units) compared with CTR (56.9±12.31 relative units) at the onset of the subsequent lactation. In conclusion, this study demonstrates that PRL inhibition by cabergoline at dry-off induces an increased proliferation and tissue remodeling of the mammary gland.

Keywords: dry period, prolactin, tissue remodeling