Excess androgen secretion in females results in hirsutism often accompanied by changes in glucose transport, e.g. diabetes. These symptoms improve with treatment of the anti-androgen Flutamide. Many actions of androgens are genomic via a nuclear androgen receptor, but non-genomic actions have also been identified, some of which are sensitive to Flutamide.
Recent studies have shown that green tea polyphenols reduce glycosuria in diabetics. They also reduce circulating levels of testosterone and benign prostatic enlargement. In the present study we investigated the non-genomic effects of androgens, the anti-androgen Flutamide and green tea catechins on glucose transport in human erythrocytes.
Fresh human red cells (obtained from R.J.N.) were pre-equilibrated with 100 mM glucose and resuspended in phosphate-buffered saline containing the ‘androgen’ under test. Following resuspension, the rate of glucose efflux was determined from light scattering changes at 650 nm.
Testosterone and 4-androstene-3,17-dione inhibited glucose exit from human erythrocytes with a Ki,test = 39.2 ± 8.9 µM and Ki,and = 44.0 ± 4.1 µM (mean ± S.E.M., n = 3-4 for each estimate). Flutamide competitively relieved the inhibitions of glucose transport by testosterone (Ki,test/Flut = 0.35 ± 0.10 µM) and androstenedione (Ki,and/Flut = 0.14 ± 0.05 µM). Flutamide also relieved phloretin-dependent inhibition of glucose exit (Ki(phloretin/Flut) = 1.75 ± 0.22 µM), suggesting that it binds exclusively to the external (sugar import site) site of GLUT1. This was confirmed as glucose binding to the external site of the glucose transporter was competitively inhibited by testosterone, K(ic ext test) = 42.8 ± 0.8 µM.
The green tea catechins also inhibited glucose exit. The catechin with the highest affinity was epicatechin 3 gallate (ECG), Ki(ECG) = 0.14 ± 0.01 µM. The major tea constituent, epigallocatechin 3-gallate (EGCG) had a Ki(EGCG) = 0.97 ± 0.13 µM. Flutamide competitively reversed both the inhibitions of EGC and EGCG. The high affinities of ECG and EGCG for the glucose transporter (GLUT1) suggest that this might be their physiological site of action.