Korean J Obstet Gynecol.  2005 Mar;48(3):628-637.

Increased expression of dopamine receptors and transporter and hypomethylation of dopamine transporter gene in uterine leiomyoma

• Kim JH
• Kim MJ
• Choo YA
• Choi YS
• Lee TS
• Kim HT

Abstract

OBJECTIVE
Dopamine plays a key role in the proliferation regulation of the smooth muscle cells. The purpose of this study was to observe the degree of expression of dopamine D1 and D2 receptors and dopamine transporter (DAT) and to evaluate the influence of methylation about control of expression of DAT in uterine leiomyoma and normal myometrial tissue.
METHODS
In 20 patients who underwent hysterectomy due to uterine leiomyoma, normal myometrial and leiomyoma specimens were obtained. The expression of dopamine D1 and D2 receptors and DAT was demonstrated by using RT-PCR and immunohistochemistry in each normal myometrium and leiomyoma. Analysis of the DNA methylation status of DAT was conducted using HpaII digestion and the methylation-sensitive PCR.
RESULTS
The mRNA level of dopamine D1 receptor was relatively higher in normal myometrium than D2 receptor and it was also unchanged in leiomyomas. However, the mRNA levels of dopamine D2 receptor and DAT in leiomyomas were much higher than normal myometrium. Consistent with elevated mRNA levels, high levels of dopamine receptors protein expression were detected by immunohistochemistry in leiomyomas. The degree of methylation at CpG sites of the area intron 1 of DAT (genomic position, +377 - +888) was decreased in leiomyomas.
CONCLUSION
These results suggest that overexpressed dopamine D2 receptor and DAT would be associated with proliferation of human uterine leiomyomas and the methylation status of the CpG island of DAT determines its expression.

Keyword

Dopamine D1 receptor; Dopamine D2 receptor; Dopamine transporter (DAT); Methylation; Leiomyoma

MeSH Terms

Animals
CpG Islands
Digestion
DNA Methylation
Dopamine Plasma Membrane Transport Proteins*
Dopamine*
Female
Humans
Hysterectomy
Immunohistochemistry
Introns
Leiomyoma*
Methylation
Mice
Myocytes, Smooth Muscle
Myometrium
Polymerase Chain Reaction
Receptors, Dopamine D1
Receptors, Dopamine D2
Receptors, Dopamine*
RNA, Messenger
Dopamine
Dopamine Plasma Membrane Transport Proteins
RNA, Messenger
Receptors, Dopamine
Receptors, Dopamine D1
Receptors, Dopamine D2