Adenomyosis is an oestrogen-dependent uterine disease where ectopic, non-neoplastic endometrium is histologically observed within the myometrium. Its incidence ranges between 5 and 70% and although presenting symptoms; menorrhagia (4050%), dysmenorrhoea (1030%) and metrorrhagia (1012%) are well known, its aetiopathology remains unclear. The neurotrophin, nerve growth factor (NGF), has been implicated in the aetiopathology of adenomyosis, especially in the tamoxifen-dosed neonatal CD-1 mouse, which develops severe adenomyosis through increased NGF expression. Preliminary data indicates that the neurotrophin system (ligands and receptors) are present in the human uterus, but have not been examined in adenomyosis.
In this study, immunohistochemistry and quantitative RT-PCR were used to examine NGF, BDNF, p75, trkA, trkB and trkC expression in human adenomyotic myometrium. The effect of oestradiol and tamoxifen on NGF mRNA levels measured in control and adenomyotic myometrial cell cultures.
Histomorphometric analyses of the immunohistochemical staining indicated an increase in NGF protein in the inner and outer myometrium of adenomyosis throughout the menstrual cycle, whilst trkC expression was unchanged. In the proliferative phase, trkB was significantly decreased throughout the myometrium and significantly increased in the secretory phase, whilst trkA showed a significant decrease only in the outer myometrium during the secretory phase; p75 was undetectable. NGF transcript levels were significantly increased in adenomyotic inner myometrium, (1.5-fold; P<0.05; Students t-test) and significantly decreased in the outer myometrium, whilst BDNF, p75, trkB and trkC transcript levels were significantly decreased by 60, 90, 50 and 35%, respectively. Furthermore, NGF transcript levels were significantly (P<0.001; one-way ANOVA; n=12) reduced in both normal (4.5-fold) and adenomyotic (1.25-fold) cultures in response to oestradiol and to a lesser extent in both normal (2.6-fold) and adenomyotic (1.36-fold) cultures by tamoxifen.
These differences suggest a possible role for the neurotrophins and their receptors in the adenomyotic myometrium and in the aetiopathology of this common disease.