In Vivo Assessment of the Regulation of Transforming Growth Factor Alpha, Epidermal Growth Factor (EGF), and EGF Receptor in the Human Endometrium by Medroxyprogesterone Acetate

Abstract

Purpose : The present study evaluated the in vivo effect of medroxyprogesterone acetate (MPA) on the localization of immunoreactive transforming growth factor alpha (TGFα), epidermal growth factor (EGF), and their common receptor (EGF-R) in the human endometrium. Methods : The study design was a randomized clinical trial enrolling 36 healthy women with regular menstrual cycles. The participants were randomly assigned into three groups: groups 1 (n = 11) and 2 (n = 17) received placebo and were submitted to endometrial biopsy during the proliferative and secretory phases of menstrual cycle, respectively; group 3 (n = 8) received MPA (10 mg/day) for 10 days followed by endometrial biopsy, which was performed during the secretory phase. Immunohistochemistry was used to localize TGFα, EGF, and EGF-R in the endometrial tissue. Results : TGFα was present markedly in the luminal and glandular epithelia but also in the periglandular stroma, with a distribution pattern similar in the three experimental groups. EGF immunostaing was equally distributed in epithelial and stromal layers of the endometrium and remained unchanged in endometrial samples from women treated with MPA compared to placebo. EGF-R was expressed only in the epithelium. The intensity of EGF-R immunostaining was higher in secretory than in proliferative endometrium and was further increased by administration of MPA (p < 0.05, chi-square test). Conclusion : The present results suggest that the progestogen-induced in vivo differentiation of secretory endometrium does not require dramatic changes in the expression of EGF or TGFα, whereas EGF-R may be up regulated.

Bone Marrow-Derived Cells from Male Donors Do Not Contribute to the Endometrial Side Population of the Recipient

“…Patients with secondary amenorrhea after transplantation received hormone replacement therapy (HRT) using a Gonadotropin-releasing hormone agonist depot (GnRH-a) (Decapeptyl 3.75, IPSEN, France) injected on day 21 of the previous cycle. Estradiol valerate (EV) (Progynova; Schering Spain, Madrid, Spain), 6 mgr daily, was initiated on day 2 of the cycle for at least 10 days, while progesterone (Utrogestan, Corne, Mexico), 800 mg per day, was added as previously described [41] – [42] . An endometrial tissue specimen was obtained with a Pipelle catheter (Gynetics Medical Products N.V, #4164 probet, Belgium) under sterile conditions from the uterine fundus at a minimum of 4 months from starting HRT.…”

Estrogen receptor alpha (ERα) phospho-serine-118 is highly expressed in human uterine leiomyomas compared to matched myometrium

“…8, we propose a possible mechanism of interaction between the ERα and growth factor signaling pathways and the regulation of these pathways by estradiol (E 2 ) and progesterone (P 4 ), which is highly supported by the data reported in this paper. This schematic shows that activation of ERα via phosphorylation at serine 118 by phospho-p44/42 MAPK is regulated by E 2 (positively) and P 4 (positively or negatively) through the up- or down-regulation of local cytokines, growth factors, and growth factor receptors [17, 21, 29, 32]. Future studies are underway to test this hypothesis.…”

EGF, TGF-α and Amphiregulin Differently Regulate Endometrium-Derived Mesenchymal Stromal/Stem Cells

“…Different spatial expression patterns were reported for other members of the EGFR family. The data on the spatiotemporal expression of several EGFR ligands diverge significantly as well [9,[14][15][16]. EGFR and some of its ligands were also detected in isolated stromal enMSC lines [17].…”