Inmaculada R. Puertes

Role of prolactin in amino acid uptake by the lactating mammary gland of the rat

The rn~rn~y gland is under hormone control during lactation. We reported that y-glutamyl trans- ferase and glutathione are involved in amino acid uptake by the lactating mammary gland [ 11. In [2,3] it was shown that ~-~ut~yi transferase activity in the mammary gland is subject to hormonal control. Thus, we investigated the hormone regula- tion of ammo acid uptake by the mammary gland of the rat and the evolution of arteriovenous differences of amino acids across the mammary gland during lac- tation. Here we report that changes in arteriovenous dif- ferences of amino acids across the mammary gland parallel those of y-glutamyl transferase activity and that prolactin plays an ~portant role in the regula- tion of ammo acid uptake by the mammary gland. 2.

Impairment of cysteine synthesis from methionine in rats exposed to surgical stress.

The activity of liver cystathionase (EC 4.4.1.1) was decreased after 3 d of stress induced by surgery. The rate of L-cysteine synthesis from L-methionine was significantly higher in isolated hepatocytes from controls than in hepatocytes from rats suffering from surgical stress. The half-life of L-[2(n)-3H]methionine was significantly higher in rats submitted to surgical stress than in controls. Plasma L-methionine:L-cystine ratio was higher in stressed rats than in controls. L-cystine uptake was significantly increased in the surgically-stressed rats when compared with the controls. All these facts are consistent with the hypothesis that the observed inhibition of cystathionase is physiologically important and that L-cysteine might be considered as an essential amino acid in cases of surgical stress.

Gamma-Glutamyl-Amino Acids as Signals for the Hormonal Regulation of Amino Acid Uptake by the Mammary Gland of the Lactating Rat

The mammary gland is a good model to study the hormonal regulation of amino acid uptake. Danazol, which decreases gonadotrophin release, causes a fall in gamma-glutamyltranspeptidase (GGT) and in amino acid uptake by the gland. Treatment of the rats with estrogens and progesterone partially reverts this effect. Treatment with gonadotrophins completely reverts it. gamma-Glutamyl-amino acids (GAA) increase the uptake of amino acids by the mammary gland in rats previously treated with bromocriptine. We suggest that GAA may act as signals to stimulate amino acid uptake and that the role of GGT may be to generate that signal.

Effect of specific inhibition of gamma-glutamyl transpeptidase on amino acid uptake by mammary gland of the lactating rat.

We showed [Biochem. J. (1981) 194, 99–102] that inhibition of γ‐glutamyl transpeptidase in vivo with serine‐borate decreases amino acid uptake by mammary gland. However, doubts arose about the validity of this inhibitor in metabolic studies because it must be used in very large amounts. New Inhibitors have been isolated, like anthglutin and acivicin, which are effective at low concentrations in vivo. Here, we show that treatment of lactating rats with these substances decreases the transpeptidase activity and the amino acid uptake by the gland. These results support the hypothesis that the γ‐glutamyl cycle functions as an amino acid transport system in mammary gland.

Effect of nitrous oxide and propofol on amino acid metabolism in neoplasic patients

In a randomized controlled clinical trial, 14 patients requiring resection of tumors were divided in two groups: one group was anesthetized with nitrous oxide [67% N2O-33% O2 (vol/vol)] and the other with propofol. Two other groups of subjects were studied: a group of patients that was undergoing orthopedic procedures and was anesthetized with nitrous oxide [67% N2O-33% O2 (vol/vol)] and a control group (fasted for 10 hrs and no anesthesia). In patients requiring resection of tumors, the blood L-methionine concentration was significantly lower and the blood amino acid pattern was significantly affected after the administration of nitrous oxide (120-310 mins) compared with values after the induction of anesthesia and before surgery. The administration of propofol (120-240 mins) did not produce any of these changes. No patients required blood transfusion during surgery, and the patients had not previously been treated with cancer chemotherapeutic agents. The administration of nitrous oxide (60-150 mins) to patients undergoing orthopedic procedures did not affect blood L-methionine. It is concluded that the administration of nitrous oxide to cancer-bearing patients, but not to those undergoing orthopedic surgery, produced major changes in amino acid metabolism; therefore, consideration should be given to the avoidance of exposure of cancer patients to nitrous oxide.