Lack of Effect of Norethindrone and Mestranol on Folacin Depletion and Repletion in Rats

The study investigated whether folacin deficiency could be produced in rats through treatment with contraceptive hormones, and whether hormonal treatment interfered with the utilization of folic acid glutamates. Folacin-depleted and folacin-sufficient rats were implanted subcutaneously with silastic capsules containing either norethindrone or mestranol, or a mixture of both, or cholesterol, or were sham operated. Three weeks after treatment, the rats received a single IP dose of [2-14C]folic acid ([14C]PteGlu) and were killed 24 hours later. Microbiological assay determinations with Lactobacillus casei showed that the rats fed the deficient diet had lower tissue folacin values, but neither hormone singly nor their combination had any effect on folacin tissue levels in either the folacin-depleted or the folacin-sufficient rats. Radioactivity retention in the kidney, but not in the liver, of folacin-depleted rats reflected the dietary depletion, but no substantial effect of the hormonal treatments on this variable was evident in either of these organs. In a second experiment, folacin-depleted rats received the same hormonal treatments that have been described above. Partial repletion of tissue folacin was achieved with equimolar doses of synthetic folic acid glutamate 7 (PteGlu7) and folic acid (PteGlu) administered by gavage. Tissue folacin determinations showed that the levels of repletion were identical in all rats regardless of hormonal treatment or whether repletion had been accomplished with PteGlu or PteGlu7. It was concluded that the rat was not susceptible to the folacin deficiency associated with the use of oral contraceptive hormones (specifically norethindrone and mestranol), and that these hormones do not affect the availability of conjugated folacin (specifically PteGlu7).