Etude de l'expression et de la régulation de PGRMC1 dans l'endomètre humain

Details

Supervisors

Henriet, Patrick

Faculty

Faculté de pharmacie et des sciences biomédicales

Degree label

Master [120] en sciences biomédicales, à finalité approfondie

Abstract

Endometriosis is a chronic gynecological disease that causes pelvic pain and infertility. It affects 10% of women of childbearing age. Since the progression of the lesions is stimulated by estrogens and suppressed by progestogens, oral contraceptives are useful to inhibit it, but a significant proportion of patients are resistant to progesterone. The absence or inactivity of the nuclear progesterone receptor explains only part of these cases and alternative response mechanisms are likely to be involved, including a pathway involving the PGRMC1 protein which is under investigation in the host laboratory. Previous work in the laboratory has shown that endometrial PGRMC1 expression increases during the proliferative phase of the menstrual cycle and then decreases during the secretory phase, suggesting inductive control by estradiol and repressive control by progesterone. The first objective of this thesis was to complete the study of endometrial PGRMC1 expression on histological sections. My results confirmed that PGRMC1 expression follows a gradient suggesting a complex transcriptional control. Furthermore, the partial colocalization of PGMRC1 and Ki67 in human endometrium and the effects of siRNA targeting PGRMC1 mRNA on stromal cell proliferation in primary culture suggest that PGRMC1 contributes to the regulation of cell proliferation in the endometrium. Experiments in primary culture were continued in an attempt to demonstrate hormonal control of PGRMC1 expression. This objective was not achieved, despite attempts to modify the model for optimization. The high stability of PGRMC1 mRNA may in part contribute to its lack of response in cell culture. Surprisingly, PGRMC1 expression was increased by the decidualization-inducing stimulus (combination of ovarian steroids and cAMP) but also by cAMP alone. These results, coupled with hormone receptor immunostaining suggesting altered activity in primary cultured cells, call into question the adequacy of the isolated cell culture experimental model to address the question of endometrial regulation of PGRMC1.