Action of Merthiolate on Gonadotropic Effect of Anterior Pituitary Extract

Abstract

The germicide, “Merthiolate”∗ (C₂H₅H_gS C₆H₄COONa), should be included in the growing list of substances which may enhance the gonadotropic effect of anterior pituitary extract. In using merthiolate as a germicide in aqueous solutions of gonadotropic pituitary hormone, we discovered by accident that the gonadotropic changes were markedly potentiated because of the presence of low concentrations of the drug.

If a dose of anterior pituitary hormone in aqueous solution at a pH of about 7.4 is administered by; subcutaneous injections distributed over several days to immature female rats and causes a moderate but clear-cut increase in ovarian weight, the same solution containing 1-5000 merthiolate (total dose 0.8 mg.) causes twice to three times as great a change as judged by the increase in ovarian weight. The merthiolate is added each day just before injection; it causes no change in the appearance of the water-clear hormone solution. An increase in the effect, roughly proportional to the change in concentration, is produced by increasing the concentration of merthiolate. Maximal potentiation occurs in immature rats receiving toxic but sublethal doses of merthiolate (0.077% or 1-1300; total dose 3.08 mg.). Concentrations of 1-10,000 or lower are without effect.

The effect of anterior pituitary extract on the testis of the immature male rat (change in seminal-vesicle weight) is also clearly potentiated by merthiolate. However, the germicide increases neither the proportion of rabbits ovulating nor the number of ruptured follicles in individual rabbits if the effects of the intravenous injection of a solution of an anterior-pituitary extract with and without merthiolate (1-5000 or 1-3000) are compared. Moreover, it does not increase the effect of even crude preparations of prolan on the ovary or testis (seminal vesicles) of the immature rat.