MENSTRUAL-CYCLE SPECIFIC EXPRESSION OF EPIDERMAL GROWTH-FACTOR RECEPTORS IN HUMAN FALLOPIAN-TUBE EPITHELIUM

We studied the expression of epidermal growth factor (EGF) receptor pr otein and messenger RNA (mRNA) in human fallopian tubes at three stage s of the menstrual cycle: early follicular (n=3), late follicular (n=3 ) and luteal (n=3). Immunohistochemical studies in the ampullary porti on of the tubes showed that specific staining was localized to the epi thelium and the vascular endothelium. Staining of the epithelium was i ntense at the late follicular and luteal stages, while it was weak at the early follicular stage. I-125-EGF binding study in the tubal plasm a membranes revealed a class of high-affinity EGF receptors. Although dissociation constants were similar between the stages, numbers of bin ding sites at the late follicular and luteal stages were significantly (P<0.01) greater than those at the early follicular stage. Western bl otting showed that tubal plasma membranes contain M(r) 170000 EGF rece ptor protein. The amounts were significantly (P<0.01, n=3) greater at the late follicular and luteal stages than those at the early follicul ar stage. Reverse transcription and polymerase chain reaction (RT-PCR) revealed that EGF receptor mRNA was expressed in all the 9 RNA sample s (n=3 for each stage) from the tubal ampullary portion. The amounts w ere significantly (P<0.01, n=3) greater at the late follicular and lut eal stages than those at the early follicular stage (by a competitive PCR). Increase in the amounts of EGF receptor protein and mRNA occurre d in association with an increase in serum oestradiol but not progeste rone levels. Next we examined whether EGF receptor and its ligands (EG F and transforming growth factor alpha) are directly induced by oestro gen. We found that specific staining for EGF receptor and its ligands in the tubal epithelium was detected (by immunohistochemistry) in post menopausal women with oestrogen replacement (n=3), but not in subjects without oestrogen replacement (n=3). These results suggested that EGF receptors in the human tubal epithelium are expressed in relation to specific stages of the menstrual cycle and that the expression may be induced by oestrogen.