EXPRESSION OF SEX HORMONE-BINDING GLOBULIN EXON-VII SPLICING VARIANT MESSENGER-RNA IN HUMAN UTERINE MYOMETRIUM AND LEIOMYOMA

We have explored the mechanism of estrogen-induced growth in human ute rine leiomyomas from the aspect of sex hormone-binding globulin (SHBG) exon VII splicing variant mRNA expression using the reverse transcrip tion-polymerase chain reaction-Southern blot and DNA sequencing analys es. The results were obtained by analysis of the missing base pairs co rresponding to the entire exon VII, which are considered to encode a p ortion of the steroid-binding site. This absence replaces 118 amino ac ids from the carboxy-terminus of SHBG with nine different amino acid r esidues due to the formation of a new stop codon at residue 334. The r atio of the SHBG variant to its wild-type mRNA levels in uterine leiom yomas was reduced, compared with that in the corresponding myometria i n individual cases, while the SHBG wild-type and variant mRNA levels s howed no significant difference during the menstrual phase. These stud ies demonstrate coexpression of SHBG exon VII splicing variant mRNA wi th its wild-type in human uterine myometria and leiomyomas. The reduce d expression of the SHBG variant to wild-type mRNA levels in leiomyoma might be involved in the intracellular estrogen-predominant milieu, p lausibly assisting in the development and growth of the leiomyoma. (C) 1997 Elsevier Science Ltd. All rights reserved.