Expression of sex hormone-binding globulin exon VII splicing variant mRNA in human uterine myometrium and leiomyoma

We have explored the mechanism of estrogen-induced growth in human uterine leiomyomas from the aspect of sex hormone-binding globulin (SHBG) exon VII splicing variant mRNA expression using the reverse transcription-polymerase chain reaction-Southern blot and DNA sequencing analyses. The results were obtained by analysis of the missing base pairs corresponding to the entire exon VII, which are considered to encode a portion of the steroid-binding site. This absence replaces 118 amino acids from the carboxy-terminus of SHBG with nine different amino acid residues due to the formation of a new stop codon at residue 334. The ratio of the SHBG variant to its wild-type mRNA levels in uterine leiomyomas was reduced, compared with that in the corresponding myometria in individual cases, while the SHBG wild-type and variant mRNA levels showed no significant difference during the menstrual phase. These studies demonstrate coexpression of SHBG exon VII splicing variant mRNA with its wild-type in human uterine myometria and leiomyomas. The reduced expression of the SHBG variant to wild-type mRNA levels in leiomyoma might be involved in the intracellular estrogen-predominant milieu, plausibly assisting in the development and growth of the leiomyoma.