Human sex hormone-binding globulin gene expression- multiple promoters and complex alternative splicing

Area of Science:

• Molecular biology
• Genetics
• Endocrinology

Background:

• Human sex hormone-binding globulin (SHBG) regulates sex steroid levels and signaling.
• SHBG gene expression is primarily controlled by a downstream promoter (P(L)), with a second promoter (P(T)) also known.

Purpose of the Study:

• To investigate the complexity of human SHBG gene transcription.
• To identify novel SHBG transcripts and their regulatory mechanisms.
• To analyze SHBG transcript expression patterns in various human tissues and cell lines.

Main Methods:

• Mapping of transcriptional start sites.
• Analysis of alternative splicing events.
• Transcriptional profiling across human tissues (prostate, breast, testis, liver, brain) and cell lines (LNCaP, MCF-7, HepG2).

Main Results:

• Human SHBG gene transcription is highly complex, with at least three promoters (P(L), P(T), P(N)) identified.
• Each promoter directs the expression of multiple transcripts through alternative splicing of exons 4, 5, 6, and/or 7.
• A novel first exon (1N) is associated with transcripts regulated by the P(N) promoter.
• SHBG transcripts are expressed in all tested tissues and cell lines, with distinct patterns and increased alternative splicing in cancer cell lines.
• A smaller immunoreactive SHBG species was detected in cancer cell lines.

Conclusions:

• The human SHBG gene exhibits a more intricate transcriptional landscape than previously understood.
• Novel alternatively spliced SHBG transcripts warrant further investigation into their functions in hormonally responsive tissues.
• Aberrant SHBG gene expression may play a role in the development of cancers, particularly in the breast and prostate.