THE ROLE OF FOLIC ACID IN HORMONALLY-INDUCED TISSUE GROWTH

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Abstract
SUMMARY: The effect of the folic acid antagonist, aminopterin, on the response of the mammary gland and uterus to oestrogen in the rat, and the pigeon crop-gland to prolactin have been investigated. Using the paired-feeding technique, it was found that the growth of the mammary glands in the spayed female rat, in response to a maximal oestrogenic stimulus, was diminished during severe folic acid deficiency. The rate of increase of glandular area relative to body surface area in the animals treated with aminopterin was considerably lower than that of the pair-fed control rats. The type of glandular structure obtained after oestrogen treatment seemed to be independent of the presence of the vitamin. The five-fold increase in uterine weight which occurred in response to a maximal oestrogenic stimulus 48 hr after the onset of treatment, was diminished after high doses of antagonist. Complete inhibition of the response was never obtained, however, even with lethal doses of antagonist begun 2 days before the oestrogen injections. The rapid increase in water uptake of the uterus and enlargement of its epithelial lining, which are characteristic of oestrogenic stimulation in this organ, were barely affected by the aminopterin treatment. In the pigeon, although no typical folic acid deficiency symptoms developed, the growth of the crop-gland in response to prolactin was reduced by prior treatment with a high dose of aminopterin (1 mg/day). Since the normal response to prolactin was restored when either folic acid or citrovorum factor was given in conjunction with aminopterin, it was concluded that the latter was acting in the capacity of a folic acid antagonist. The mechanism of action of folic acid in hormonally-induced growth is discussed in the light of these findings.