title: Regulation of bcl-2 gene family members in human endometrium by antiprogestin administration in vivo.
abstract: It is likely that the changes which occur in the endometrium throughout the menstrual cycle involve apoptosis, and that expression of associated genes, such as the bcl-2 family, are regulated by sex steroids. The aim of this study was to investigate the presence of bcl-2, Bax and oestrogen receptor proteins in secretory endometrium collected from ten patients with normal ovulatory cycles 4 or 6 days after the LH surge, and on the same days in a subsequent cycle in which the formation of secretory changes was inhibited by the administration of the antiprogestin mifepristone (RU486) 2 days after the onset of the LH surge. Since some stromal cells display positive immunoreactivity, leucocyte subpopulations of macrophages (CD68-positive) and large granular lymphocytes (CD56-positive) were identified in serial sections. After administration of mifepristone on day 2 after the LH surge, a significant increase in bcl-2 immunoreactivity was observed in glandular and surface epithelium. A positive correlation (0.874) with nuclear oestrogen receptor immunoreactivity in endometrial glands was demonstrated. Subsets of stromal cells, identified as CD68-positive macrophages and CD56-positive large granular lymphocytes displayed positive immunoreactivity for the bcl-2 epitope, which was unaffected by mifepristone administration. Bax immunostaining was similar in control and antiprogestin-treated endometrium. These data indicate that antiprogestin administration inhibits progesterone downregulation of steroid receptors in endometrial glands, resulting in persistence of a proliferative endometrium and accompanying bcl-2 secretion.
authors.affiliation: Department of Obstetrics and Gynaecology, University of Edinburgh, UK.
authors.forename: H O
authors.initials: HO
authors.lastname: Critchley
authors.forename: S
authors.initials: S
authors.lastname: Tong
authors.forename: S T
authors.initials: ST
authors.lastname: Cameron
authors.forename: T A
authors.initials: TA
authors.lastname: Drudy
authors.forename: R W
authors.initials: RW
authors.lastname: Kelly
authors.forename: D T
authors.initials: DT
authors.lastname: Baird
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D017209:Apoptosis / Q000235:genetics; D019002:CD56 Antigen / Q000032:analysis; D004717:Endometrium / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D019254:Genes, bcl-2; D006727:Hormone Antagonists / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D008183:Luteal Phase; D015735:Mifepristone / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000187:drug effects; D051028:bcl-2-Associated X Protein; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D019002:CD56 Antigen; D006727:Hormone Antagonists; D015735:Mifepristone; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D051028:bcl-2-Associated X Protein; C494826:BAX protein, human; C067980:CD68 antigen, human; D000097382:CD68 Molecule