Some Effects of Steroid Hormones and Kynurenine on Tryptophan and its Conversion to 5-Hydroxytryptamine

Abstract

The relationship of certain steroid hormones to mood state in humans and to biochemical parameters related to 5-hydroxytryptamine function in the brains of mice have been studied. Cortisol and "free" tryptophan showed significant relations with mood in puerperal women. Cortisol, oestradiol and mestranol failed to affect the binding of tryptophan to albumin in vitro whereas a very high concentration of norethisterone increased "free" tryptophan. Brain 5-HT turnover was measured in the mouse after cortisol, a combination of norethisterone and oestradiol, and in different stages of the oestrus cycle. A high dose of cortisol reduced turnover, after 24 hr. pretreatment whereas a lower dose, or repeated dosing with a low dose had no erfect. A low-dose combination of norethisterone and oestradiol had no effect on turnover, after 14 day pretreatment. A slight reduction in brain 5-HT levels and an increase in turnover were found in oestrus, compared with dicestrus animals. The effects of these hormones on plasma and brain levels of the tryptophan metabolite, kynurenine, were studied. A low-dose combination increased plasma kynurenine without affecting brain kynurenine. Cortisol was found to decrease plasma kynurenine levels after 24 hr. pretreatment, but had no effect on brain levels. The mechanism of uptake of kynurenine into brain was investigated. | There appear to be two mechanisms of uptake, one of which is active. Kynurenine failed to affect the in vitro uptake of 5-hydroxytryptamine. Di.-kynurenine was found to reduce plasma tryptophan after i2 hr. pretreatment, but increased brain tryptophan after 30 min. A biphasic effect of DL-kynurenine was found on brain 5-hydroxytryptamine turnover, a low dose reduced turnover, whereas higher doses had no effect on turnover.