Human efflux transport of testosterone, epitestosterone and other androgen glucuronides

Abstract

Androgens are conjugated in the liver to glucuronides that are excreted in urine  Basolaterally located MRP3 is a high affinity transporter for androgen glucuronides  Apically located MRP2 is a low affinity transporter for androgen glucuronides  Apically located BCRP does not transport androgen glucuronides  High MRP3-mediated transport agrees with urinary excretion of androgen glucuronides

Novel inhibitors of breast cancer resistance protein (BCRP, ABCG2) among marketed drugs

“…In addition, it is found on the apical side of brain capillary endothelial cells in the blood-brain barrier (Uchida et al, 2011), and to a smaller extent, in the apical membranes of hepatocytes (Burt et al, 2016) and kidney proximal tubule cells (Cheung et al, 2019). BCRP transports a wide range of compounds, ranging from drugs such as sulfasalazine (Sáfár et al, 2021), various antineoplastics (Mao and Unadkat, 2015) and statins (Deng et al, 2021), to natural products (Enokizono et al, 2007;Sesink et al, 2005), carcinogens (Ebert et al, 2005;Pavek et al, 2005;van Herwaarden et al, 2006) and endogenous compounds, such as steroid metabolites (Järvinen et al, 2018(Järvinen et al, , 2020, urate (Woodward et al, 2009) and porphyrins (Jonker et al, 2002).…”

Testosterone amendment alters metabolite profiles of the soil microbial community

“…The steroid hormones are phylogenetically conserved but are newly prevalent in the environment (Alon et al, 2007;Kolpin et al, 2002). Human and animal wastes are a major source of hormones in the environments (Casey et al, 2004;Jarvinen et al, 2020). Naturally produced hormones are found in human and livestock waste, and synthetic hormones are found in manure (Casey et al, 2004).…”

Normalized Testosterone Glucuronide as a Potential Urinary Biomarker for Highly Variable UGT2B17 in Children 7–18 Years

“…TG/AG is more indicative of hepatic UGT2B17 expression, considering the sites of androgen synthesis and the relative systemic blood flow to the liver vs. the intestine. However, up to 10% of TG also undergoes enterohepatic recycling, so systemic TG/AG also incorporates intestinal UGT2B17, although more studies are needed on co‐regulation of hepatic and intestinal UGT2B17. Numerous enzymes are involved in steroidogenesis and pubertal development .…”

“…TG/AG also cannot be used when UGT2B7 expression is significantly affected, such as cirrhosis . Moreover, efflux transporters multidrug resistance‐associated protein 2 and multidrug resistance‐associated protein 3 contribute to the apical and basolateral transport, respectively, of both TG and AG in the liver, intestine, and kidneys . Both transporters show low interindividual variability as well as insignificant ontogeny in the kidneys and liver .…”