Rapid and structure-specific cellular uptake of selected steroids

• DOI: 10.1371/journal.pone.0224081
• Publication Date: 2019-10-17T18:00:15Z
• Authors: Jeffrey M. McManus; Kelsey Bohn; Mohammad Alyamani; Yoon-Mi Chung; Eric A. Klein; Nima Sharifi
• Keywords: Lipophilicity; Steroid hormone

Steroid hormones and their respective nuclear receptors are essential mediators in numerous physiologic pathophysiologic processes, ranging from regulation of metabolism, immune function, reproductive processes to the development hormone-dependent cancers such as those breast prostate. Because steroids must enter cells before activating receptors, understanding mechanisms by which cellular uptake occurs is critical, yet a clear these has been elusive. It generally assumed that diffusion-driven similar across various whereas an elevated concentration thought reflect active uptake, but assumptions have not directly tested. Here we show intact rapidly accumulate free markedly concentrations. This effect varies widely depending on steroid structure; more lipophilic reach Strong preferences exist for 3β-OH, Δ5-steroids vs. 3-keto, Δ4-structural features progestogens androgens. Surprisingly, steroid-structure-specific do require cell viability, implying passive mechanism, occur derived multiple tissue types. Physiologic relevance suggested structure-specific human prostate compared with serum. On other hand, presence serum proteins vitro blocks much, all, accumulation, while still permitting substantial amount accumulation certain steroids. Our findings suggest both make important contributions process. The role passive, lipophilicity-driven previously largely unappreciated, its existence provides context studies transport action vivo.