Identification of an alternate promoter in the rat androgen-binding protein/sex hormone-binding globulin gene that regulates synthesis of a messenger RNA encoding a protein with altered function.

Published

Journal Article

Extracellular androgen-binding proteins (ABP) are thought to modulate the regulatory functions of androgens. These proteins, which are secreted by the testis (ABP) and liver [sex hormone-binding globulin (SHBG)], are encoded by the same gene. In a previous study, the rat ABP/SHBG gene was sequenced, and a promoter (P1) was identified by primer extension. This promoter regulates synthesis of the mRNA that encodes secreted testicular ABP and fetal liver SHBG. In this study, the P1 transcriptional start site in testis and fetal liver was confirmed by RNase protection assays. We also identified an alternate promoter (PA) in the ABP/SHBG gene located 15 kilobases up-stream from the previously characterized testicular promoter (P1). The PA region has the characteristics of a GC-rich housekeeping-type promoter. RNAase protection and primer walking experiments with RNA polymerase chain reaction identified a region where the major sites of transcription initiation occur. Promoter PA directs the synthesis of alternate ABP RNAs, which contain an alternate exon 1 (exon A) sequence. One alternate ABP RNA, which contains exons A and 2-8 sequences, is expressed in testis, fetal liver, and brain. This alternate ABP RNA encodes an ABP-like protein (46,000 daltons) with an altered N-terminal sequence without a secretory signal peptide. Expression of the ABP-like protein in COS cells revealed that it is not secreted and does not appear to bind dihydrotestosterone. Another similar alternate ABP RNA is missing exon 6 sequence and encodes a nonsecretory truncated protein (28,000 daltons) that does not bind androgen. The functions of the ABP-like proteins are not obvious, but their functions are clearly different from secreted ABP and SHBG.

Full Text

Duke Authors

Cited Authors

  • Sullivan, PM; Wang, YM; Joseph, DR

Published Date

  • May 1993

Published In

Volume / Issue

  • 7 / 5

Start / End Page

  • 702 - 715

PubMed ID

  • 7686253

Pubmed Central ID

  • 7686253

Electronic International Standard Serial Number (EISSN)

  • 1944-9917

International Standard Serial Number (ISSN)

  • 0888-8809

Digital Object Identifier (DOI)

  • 10.1210/mend.7.5.7686253

Language

  • eng