Influence of Sex Hormones on Tolerance to Aminopterin. ∗

Abstract

Folic acid as a dietary essential for proper biological activity of estrogen has been demonstrated by the reduction of feathering (1) and oviduct response(2) in stilbestrol-treated chicks, absence of normal estrogen response in immature monkeys (3) and ovariectomized rats (4) on folic acid deficient diets. Impairment of reproductive performance of rats (5) results from a pregestational folic acid deficient diet which is further accentuated by the addition of an antifolic acid chemical. The folic acid antagonist, aminopterin (4-amino-pteroylglutamic acid) used to induce a deficiency, decreases (6) the oviduct response to estrogen in newly metamorphosed frogs and interferes (7) with the depressive influence of estradiol on the rat prostate. A quantitative relationship exists between folic acid and estrogen(2); the frog's oviduct response is increased by folic acid(6). Aminopterin possesses no androgenic activity(7) itself and does not interfere with androgen stimulation. However, a folic acid deficiency produces a more effective comb growth response to androsterone in chicks (4).

Folic acid, therefore, might be instrumental in inhibiting testosterone induced tissue hypertrophy and a deficiency may be the instrument for inhibition of estrogen induced tissue hypertrophy. Since a quantitative relationship between folic acid and estrogen has been established, indicating a higher estrogen response with greater folic acid intake(2), it might be conceivable that the folic acid requirement is increased in estrogen administration. Hertz(2) has pointed out the destruction of bone marrow by prolonged administration of stilbestrol, which might represent an increased folic acid requirement for bone marrow protection. If the sex hormones influence the folic acid requirement of the body, the measurement of tolerance to an induced folic acid deficiency in the presence and absence of these hormones should demonstrate an appreciable difference. Tolerance to aminopterin, a competitive vitamer, serves as a means of quantitatively determining this factor.