Hormonal regulation of leucine catabolism in mammary epithelial cells

Abstract

Branched-chain amino acids (BCAA) are actively taken up and catabolized by the mammary gland during lactation for syntheses of glutamate, glutamine and aspartate. Available evidence shows that the onset of lactation is associated with increases in circulating levels of cortisol, prolactin and glucagon, but decreases in insulin and growth hormone. This study determined the effects of physiological concentrations of these hormones on the catabolism of leucine (a representative BCAA) in bovine mammary epithelial cells. Cells were incubated at 37 °C for 2 h in Krebs buffer containing 3 mM D-glucose, 0.5 mM L-leucine, L-[1-14C]leucine or L-[U-14C]leucine, and 0-50 μU/mL insulin, 0-20 ng/mL growth hormone 0-200 ng/mL prolactin, 0-150 nM cortisol or 0-300 pg/mL glucagon. Increasing extracellular concentrations of insulin did not affect leucine transamination or oxidative decarboxylation, but decreased the rate of oxidation of leucine carbons 2-6. Elevated levels of growth hormone dose dependently inhibited leucine catabolism, α-ketoisocaproate (KIC) production and the syntheses of glutamate plus glutamine. In contrast, cortisol and glucagon increased leucine transamination, leucine oxidative decarboxylation, KIC production, the oxidation of leucine 2-6 carbons and the syntheses of glutamate plus glutamine. Prolactin did not affect leucine catabolism in the cells. The changes in leucine degradation were consistent with alterations in abundances of BCAA transaminase and phosphorylated levels of branched-chain α-ketoacid dehydrogenase. Reductions in insulin and growth hormone but increases in cortisol and glucagon with lactation act in concert to stimulate BCAA catabolism for glutamate and glutamine syntheses. These coordinated changes in hormones may facilitate milk production in lactating mammals.

Dietary l-leucine supplementation enhances intestinal development in suckling piglets

“…Emerging evidence shows that l-leucine has a signaling role in the small intestine to activate the mammalian target of rapamycin (mTOR), thereby stimulating protein synthesis and inhibiting proteolysis (Rhoads and Wu 2009). Similar functions of l-leucine have also been reported for other tissues, including skeletal muscle (Columbus et al 2015;Davis et al 2010;Escobar et al 2006) and mammary gland tissue (Lei et al 2011(Lei et al , 2013. Thus, either dietary supplementation with l-leucine or provision of leucine-rich meal leads to increased protein accretion in tissues (Li et al 2011a;Yin et al 2010).…”

“…The intestinal development of neonates depends on the supplies of nutrients, growth factors, and hormones (Lei et al 2013;Wu et al 2013;Zabielski et al 2008). Glutamate, glutamine and aspartate are major metabolic fuels for the small intestine to maintain its digestive function and to protect the integrity of the intestinal mucosa in piglets (Wu 2009).…”

Correlations between Milk and Plasma Levels of Amino and Carboxylic Acids in Dairy Cows

“…It is known that these amino acids are of great importance for neonatal health, growth and development. 47 …”

Production of free glutamate in milk requires the leucine transporter LAT1

“…This expression pattern for LAT1 is similar to the one reported previously by Aleman et al (3) in rats and Manjarin et al (20) in pigs and probably respond to the specific hormonal changes that occur during pregnancy and lactation. Recent studies have shown that Leu transamination and decarboxylation are stimulated by cortisol in rat mammary tissue and the glucocorticoid receptor NR3C1 curiously overlaps with the expression of the major milk proteins ␣-lactalbumin and ␤-casein in the porcine mammary gland (15,19). In contrast, the expression of the growth hormone receptor (growth hormone inhibits Leu transamination) tended to decreases with lactation.…”

“…The transamination reaction results in the net transfer of nitrogen from BCAA to dispensable amino acids such as Glu, and this process is hormonally regulated. Insulin and growth hormone inhibit BCAA transamination, whereas cortisol and glucagon increase it (9,15,17). This high BCAA demand suggests active BCAA transport in mammary cells.…”