Dr. Joseph et al., THE ALTERNATE N-TERMINAL SEQUENCE OF RAT ANDROGEN-BINDING PROTEIN SEXHORMONE-BINDING GLOBULIN CONTAINS A NUCLEAR TARGETING SIGNAL/, Endocrinology, 137(3), 1996, pp. 1138-1143
Androgen-binding protein/sex hormone-binding globulin (ABP/SHBG) is an
extracellular earlier protein of androgens and estrogens. The protein
regulates the bioavailability of sex steroids, and expanding evidence
suggests that it also acts as a hormone. ABP/SHBG is secreted by Sert
oli cells and hepatocytes using a signal peptide. An alternate messeng
er RNA encodes a nonsecreted form of ABP/SHBG (Alt-ABP/SHBG) that has
a unique N-terminal amino acid sequence. In this study, we report that
the alternate N-terminal sequence targets Alt-ABP/SHBG to the nucleus
instead of the endoplasmic reticulum. The recombinant Alt-ABP/SHBG ex
pressed in COS-7 cells was located in the nucleus, whereas recombinant
cellular ABP/SHBG was primarily cytoplasmic. Neither dihydrotestoster
one nor estradiol had any detectable effect on the ABP/SHBG or Alt-ABP
/SHBG cellular location. Although the function of the nuclear Alt-ABP/
SHBG is unknown, it may act as a modulator of androgen receptor- and/o
r estrogen receptor-mediated gene regulation.