Muscle architecture in uterine leiomyomas and 5-hydroxytryptamine type 2A receptor

Abstract

Serotonin (5-HT) is a paracrine hormone which is active on tissues characterized by an elevated cellular turnover. The 5-hydroxytryptamine type2 receptor family (5-HT2) is involved in several physiological functions in smooth muscles, including stimulation of cellular mitosis, lysis of extracellular matrix, and contractility, which facilitates its participation in the maintenance of the normal organ architecture [1,2]. Previous studies have suggested the presence of 5-HT2 receptor mRNA in cultured uterine cells [3] and, in a comparison of the expression of the 5HT2 subgroup A receptor (5-HT2A) in smooth muscle myometrial cells of pregnant and nonpregnant rats, demonstrated a 5-HT-dependent remodeling process for reduction of postpartum uterine volume and restoration of the normal cytoarchitecture [4]. Biochemical evidence for the presence of 5-HT2A receptors in normal human myometrium and potential changes in their expression and functional architectural role remain to be seen. The aim of the present study was to explore how uterine leiomyomas (tissue that undergoes hyperplasia, disorganized cellular architecture, and loss of contractility) could represent a model for measuring 5-HT2A receptor mRNA in leiomyomatous and normal myometrial tissue. Biopsies of leiomyomatous and normal myometrial tissue were collected from 14 women who underwent simple hysterectomies for multiple uterine leiomyomas. Histologic analysis in 71.4% (10/14) of the cases confirmed the diagnosis of typical leiomyoma, while in 28.6% (4/10) it revealed the presence of a mitotic index up to 5 mitoses/highpower field and diagnosed hypercellular leiomyoma. The tissue samples were processed using real-time polymerase chain reaction (PCR), which was chosen as the method to quantify the genetic expression of 5-HT2A receptors within the tissues. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was used to evaluate each patient's cellular genetic expression and to calculate the normalization index for each tissue ([HTR2A-RNA]/[GAPDH-RNA]=K). The difference in 5-HT2A expression between normal myometrial and leiomyomatous tissue was evaluated by