Prolactin-inhibitor cabergoline enhanced the mammary remodeling during drying-off in dairy cows

In ruminants, the early phase of drying-off is a period of intense mammary gland remodeling that has great consequences on the next lactation and that is marked by the cessation of prolactin (PRL) release. To assess the effect of PRL inhibition on mammary remodeling, 14 Holstein dairy cows were injected with a single i.m administration of 5.6 mg cabergoline (n = 7) or placebo (n = 7) just after the last milking before drying-off. Mammary biopsy samples were collected one week before drying-off (D-6), at D1 and D8 and used for zymography analyses. Mammary secretion samples (290 mL) were collected using a teat-cannula once during lactation (D-6) and at D1, D2, D3, D4, D8 and D14 after the drying-off. The mammary secretion samples were used for SCC, Na+, K+ and BSA determinations and zymography analyses. Mammary epithelial cells (MEC) were purified from mammary secretions after centrifugation and immunocytochemical binding. Blood samples were collected before and after the morning mammary secretion collection for PRL determination. Cabergoline treatment decreased the blood PRL level from D1 to D8 compared with control treatment (P < 0.001). SCCwas 2.4 fold higher in cabergoline treated cows than in control cows (P < 0.01). In addition, cabergoline induced an increase in MEC count (P = 0.04) with a reduction of their viability on D3 and D4. No significant cabergoline effect was observed on Na+ and BSA except a tendency for a higher K+ content in the mammary secretions of cabergoline treated cows (P = 0.06 at D1), suggesting a small increase in the tight junction opening in the mammary gland. In mammary tissue, cabergoline increased the activity of MMP-2 (matrix metalloproteinases) after drying-off (1.4 fold, P ≤ 0.01). In mammary secretion, cabergoline increased the activity of MMP9 (1.7 fold, P < 0.05). Cabergoline treatment was efficient to enhance the extracellular matrix mammary remodeling, the MEC exfoliation and the migration of somatic cells responsible for the mammary gland remodeling. The mammary gland remodeling induced by the lower plasmatic PRL concentration may only be in part explained by a higher tight junction opening.