The ascorbic acid (AA) concentration in anterior pituitary and blood plasma was measured by the Roe-Kuether method in control rats and rats treated with oestradiol benzoate alone, methylene blue alone and with both oestradiol and methylene blue. We have found that methylene blue alone caused a significant drop in hypophyseal both AA and plasma AA concentrations. Methylene blue treatment prevented the increase in plasma AA concentration in oestradiol benzoate-treated rats.
Male rats received estradiol benzoate in a long acting microcrystalline suspension (1 mg/rat i.m., twice a week), methylene blue (MB) 0.5 % in the food and the combination of estradiol and MB. After three weeks, MB partially inhibited the growth response of the anterior pituitary to estradiol and it partially inhibited the increase of cAMP content in anterior pituitary. The increase of anterior pituitary cGMP content was not modified by MB, neither the ratio cAMP/cGMP in the anterior pituitary which, however, decreased after estradiol. This decrease was not modified by MB. On the other hand, the prolactin (PRL) increase in the blood after estradiol was inhibited by MB, although the prolactin content in the anterior pituitary was not. Methylene blue alone did not change blood prolactin concentration, but it unexpectedly elevated blood thyroxine levels and this effect was partially inhibited by simultaneous estradiol treatment.
The administration of oestrogens increases the hepatic synthesis and plasma level of ceruloplasmin both in man and laboratory animals. Methylene blue, an oxidizing agent and inhibitor of soluble guanylate cyclase, is widely used to block the effects of endothelium-derived relaxing factor (nitric oxide). We describe the inhibitory effect of methylene blue on the increase of ceruloplasmin plasma level in rats during oestradiol treatment.