Biologically Active Steroids Activate Receptor-Bound Human Sex Hormone-Binding Globulin to Cause LNCaP Cells to Accumulate Adenosine 3′,5′-Monophosphate*

Publisher Website
Google Scholar
Abstract
The binding of human sex hormone-binding globulin (SHBG) to a human prostatic cancer cell line (LNCaP) and the results of that binding were examined. Membranes derived from LNCaP cells bound unliganded SHBG on two sets of sites whose affinities were: Kal = 3.1 .+-. 1.6 .times. 1010 M-1 and Ka2 = 8.7 .+-. 4.3 .times. 106 M-1. Intact cells also bound SHBG, but even after 6 h, less than 10% of specifically bound SHBG was internalized. This observation speaks against a role for the membrane binding of SHBG in steroid transport across cell membranes. When LNCaP cells were prebound with SHBG, addition of dihydrotestosterone or estradiol resulted in a dose-dependent increase in intracellular cAMP. SHBG in the absence of steroids or dihydrotestosterone in the absence of SHBG was without effect. 2-Methoxyestradiol, a steroid metabolite without biological activity, but which binds to SHBG more tightly than dose estradiol, was also without effect. These observations demonstrate a potentially important role for SHBG as a regulator of cell function of steroid hormones, one that does not require that the steroid interact with a steroid receptor.

This publication has 19 references indexed in Scilit: