The proper expression of SHBG by the placenta and fetal liver during growth may be significant in maintaining normal fetal exposures to androgens emanating from both the mother and the fetus itself. Cnsequently, dfferences in the levels of SHBG may influence sex steroid bioavailability and cellular effects with resultant clinical ramifications (Hammond & Bocchinfuso, 1995). Crrently, i is known that synthesis of SHBG is under multifactorial control mechanisms including metabolic, hrmonal and nutritional impacting on SHBG levels. Mreover, gnetic predisposition may also contribute in the variation of the levels SHBG.
Nt only therefore are environmental factors critical in SHBG level variation but also genetic factors come into play. Gven the clinical importance of the SHBG gene, nmerous studies have evaluated the potential link between polymorphisms of the SHBG gene and serum SHBG levels that can be relate to pathogenesis of several clinical conditions. A such, plymorphisms within the coding sequence and potentially within the regulatory sequence of SHBG gene which modulate production and metabolism of the protein is useful in genetic underpinning of its activity in humans (Xita, Catzikyriakidou & Georgiou, 2003).
Te human SHBG is encoded by a 4-kb gene found within the short arm (p12-p13) of chromosome number 17. Tis vital gene possesses a total of eight exons. Eon number 1 contains the coding sequence for the SHBG secretion signal polypeptide. I addition, Eon 1 contains the first few amino-terminal residues of the mature secreted protein. Eons 2 to 8 code two flanking laminin-G domains. Te N-terminal G sphere of the SHBG is responsible for the transport of steroids. Hwever, te functional importance of C-terminal domain of SHBG is not well elucidated.
Tis domain usually contains two sites for N-glycosylation. There are two main SHBG transcripts that have been recognized, ech emanating from different promoters. Te first chief transcript codes a precursor for the secreted (plasma) form of SHBG and was initially reported in the liver tissue. Te second principal transcript encodes a protein of unknown functionality which was originally described in the testis. Te two transcripts show differences in their 5’ sequences and in the absence of exon 7 in the second transcript & Bocchinfuso, 1995).
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