Effect of cortisol on mammary tight junction (TJ) permeability in lactating dairy cows

Abstract

Intact mammary epithelial TJ are important for milk synthesis. Recent in vitro studies indicate that glucocorticoids are important for maintenance of mammary TJ. In the present study, we examined the effects of cortisol on mammary TJ integrity in vivo. In two experiments, endogenous levels of cortisol in plasma were manipulated by challenging cows with (0.05 mg, 40 IU; i.v.) adrenocorticotropic hormone (ACTH 1–24 ) or by inducing transport-related stress. In experiment 1, 20 cows were subjected to an ACTH challenge 4, 2, or 1 h before milking, or no challenge (control). In experiment 2, 2 h before milking, 15 cows were challenged with ACTH, transported for 2 h, or used as controls. Blood samples were collected at −5, 60, and 120 min following the start of treatments. Decreased plasma lactose and increased milk K content were used as indicators of TJ permeability. Both ACTH and transport caused a 6-fold increase (P < 0.01) in plasma cortisol at 60 min. Time of ACTH challenge (exp. 1) did not affect plasma lactose, allowing the data to be pooled. ACTH decreased plasma lactose in experiment 1 (−5 vs 60 vs 120 min: 28.0 a vs 26.9 a vs 24.9 b ± 0.8 M, a,b P < 0.05) and experiment 2 (26.1 a vs 24.6 a vs 23.6 b ± 0.8 M, a,b P < 0.01), whereas K content in milk increased (exp. 1, control vs 4 vs 2 vs 1 h: 31.8 a vs 32.1 a vs 32.0 a vs 33.5 b ±0.2 mmol l , a,b P < 0.01; exp. 2, control vs ACTH: 41.1 vs 42.1 ±0.4 mmol l , P < 0.01). These changes are consistent with decreased TJ permeability. Moreover, these changes occurred rapidly (≤ 1 h). Despite elevated cortisol levels with transport, no changes in plasma lactose were observed, but K in milk increased (control vs transport: 40.9 vs 42.1 ± 0.4 mmol l , P < 0.05). This variable response with stress may be due to increased secretion of epinephrine, overiding the beneficial effects of cortisol on TJ. In conclusion, our data, obtained in vivo, support the findings of recent in vitro studies that glucocorticoids play a role in maintaining the integrity of TJ in the epithelium of the mammary gland.