title: Glutathione secretion into rat milk and its subsequent gamma-glutamyltranspeptidase-mediated catabolism.
abstract: Reduced glutathione (GSH) is a critical cellular antioxidant and a cofactor for enzymes that detoxify carcinogens. GSH is present at high concentrations in all mammalian tissues, including mammary gland tissue (1- 2 mM), and recent studies indicate that the tripeptide may also be present in milk. The present study examined the hypothesis that GSH is secreted into rat milk, and that some of the secreted GSH is degraded by the ectoenzyme gamma-glutamyltranspeptidase (GGT) within the milk space. To test this possibility, milk was collected over a 4-hour period in anesthetized, 9- to 11-day postpartum Wistar rats, as well as in similar rats treated with the GGT inhibitor acivicin. GGT enzymatic activity was relatively high in rat mammary tissue, and acivicin was able to inhibit most ( approximately 80%), but not all of this activity. In control animals, GSH was present in milk, although at a relatively low concentration of approximately 20-25 microM. However, after treatment with acivicin, milk GSH concentration increased 3- to 4-fold. Most of the glutathione was in the reduced form, as no GSSG was detected (<2 microM) in any of the milk samples. These results demonstrate that GSH is secreted into rat milk, but that a large fraction of the secreted GSH is degraded by the ectoenzyme GGT. Taken together with previous studies indicating the presence of GSH synthetic and catabolic enzymes in mammary tissue, these data suggest that the mammary gland has a functional gamma-glutamyl cycle. This cycle may contribute to the secretion of cysteine into milk, which is a rate-limiting amino acid for neonatal growth and development.
authors.affiliation: Development Research Laboratories, Banyu Pharmaceutical Company, Osatogun, Saitama, Japan.
authors.forename: Noboru
authors.initials: N
authors.lastname: Fujikake
authors.forename: Nazzareno
authors.initials: N
authors.lastname: Ballatori
mesh_terms: D000818:Animals; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D007555:Isoxazoles / Q000494:pharmacology; D008321:Mammary Glands, Animal / Q000201:enzymology; D008892:Milk / Q000187:drug effects / Q000378:metabolism*; D009994:Osmolar Concentration; D051381:Rats; D017208:Rats, Wistar; D005723:gamma-Glutamyltransferase / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D007555:Isoxazoles; D005723:gamma-Glutamyltransferase; D005978:Glutathione; C006303:acivicin