Interaction of steroids with the transport system of glucose in human erythrocytes

Abstract

Steroids inhibit the exchange transport of glucose in human erythrocytes. The extent of inhibition is roughly correlated to the affinity of the steroids to the membrane lipids. All C-21-steroids tested show a competitive inhibition while the C-19-steriods show different types of inhibition. 5Beta-androstane-3,17-dione acts as a competitive inhibitor. The inhibition by testosterone is of mixed type, while with androst-4-ene-3,17-dione and 5alpha-androstane-3,17-dione a non-competitive inhibition is observed. In this case two inhibitor molecules can be bound per transport molecule. The "non-competitive" inhibitors compete also to some extent with the glucose binding. This effect, however, is at high inhibitor concentrations masked by the more powerful non-competitive inhibition. Competitive and non-competitive inhibitors compete with each other. The structural requirements for the different types of inhibition are discussed.

Central Nervous System (CNS) Delivery of Glucocorticoids Is Fine-Tuned by Saturable Transporters at the Blood-CNS Barriers and Nonbarrier Regions

“…The broadly selective inhibitor probenecid used by Steffgen et al (41) may have effects on the oat, oatp, or multidrug resistance associated protein transporter families, also making these transporters candidates for those mechanisms seen here. Furthermore, GRs have been shown to modulate or inhibit the transport of known substrates of glucose transporters in rodent and human cells (9–12) and some OCT transporters in rat and human cells (42, 43). …”

“…It is now known that GCs also interact with glucose transporters in human cells (9–12) and also the efflux transporter, P-glycoprotein (P-gp) (13–15) in murine cells, and members of the organic anion transporter polypeptide (oatp) family in rat cells (16, 17). These transporters have been identified at the rodent and human BBB and choroid plexuses (18–24).…”

Increased heinz body formation and impaired erythrocyte pentose phosphate shunt function during pregnancy

“…Although hepatic function may be impaired during pregnancy when measured by bromsulphthalein excretion [28], the subclinical nature of this defect makes it an unlikely contributor to shunt dysfunction. The steroid sex hormones pregnenolone and progesterone have been shown to have inhibitory effects on red cell glucose transport [29] and G6PD activity [30]. Neither physiologic concentrations of these hormones [31,32] nor concentrations as high as 40 pM could be observed to inhibit pentose shunt activity in our assay system.…”

Resolution of the direct interaction with and inhibition of the human GLUT1 hexose transporter by resveratrol from its effect on glucose accumulation

“…Our data indicate that resveratrol interacts with sites on the transporter involved in the binding or transport of hexoses and that this interaction is also responsible for interfering with cytochalasin B binding. Several reports in the literature indicate that the endofacial cytochalasin B binding site can promiscuously interact with a variety of different chemical entities, including steroids and benzoic acid derivatives (19,31,32). There is room therefore for the possibility that binding to the same site may explain the inhibitory action of cytochalasin B, gossypol, tyrphostin A47, and resveratrol on glucose transport facilitated by GLUT1.…”