Loss of alternately spliced messenger RNA of the luteinizing hormone receptor and stability of the follicle-stimulating hormone receptor messenger RNA in granulosa cell tumors of the human ovary

Abstract

Objectives: The expression of messenger RNA (mRNA) for the LH (LHR) and FSH receptors (FSHR) was examined in normal human corpora lutea and granulosa cell tumors.

Methods: Expression was examined by RT/PCR and DNA sequencing techniques.

Results: The full-length (FL) coding region and seven additional isoforms were identified for normal LHR mRNA. Isoform 1 had portions of exons II and III deleted, and isoform 2 had exon IX omitted. Isoform 3 also had portions of exons II and III deleted and all of exon IX deleted. Exons III through VI were missing in isoforms 4-7. Isoform 5 also had exon IX omitted, and isoform 6 also had part of exon XI missing. Isoform 7 also had exon IX and part of exon XI deleted. An aberrant migration pattern of the LHR mRNA isoforms was observed for granulosa cell tumors with FIGO Stage I-IV. Five tumor samples of Stage III-IV had many isoforms absent. Seven Stage I samples had aberrant migration patterns that depended on the size of the tumor. As the size of the tumor increased the aberrant migration pattern of the LHR mRNA isoforms was more pronounced and some isoforms were not detected. The FL and at least one additional isoform were identified for FSHR mRNA. Isoform 1 had regions of exons IV and V deleted. The FSHR mRNA isoforms had a similar migration pattern for the normal ovary and the granulosa cell tumors.

Conclusions: Alternately spliced forms of mRNA for the LHR and FSHR exist for normal human ovary and granulosa cell tumors. The aberrant migration and missing LHR mRNA isoforms in granulosa cell tumors do not appear to result from general genomic instability associated with tumor progression. These findings are important to understand the role of alternate splicing in the regulation of LHR and FSHR expression in different pathological states.