Open AccessRegulation of bcl-2 gene family members in human endometrium by antiprogestin administration in vivo
Author(s) -
Hilary O. D. Critchley,
Ting Sun,
Sharon Cameron,
T. A. Drudy,
Regis B. Kelly,
D. T. Baird
Publication year - 1999
Publication title -
reproduction
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.208
H-Index - 136
eISSN - 1741-7899
pISSN - 1470-1626
DOI - 10.1530/jrf.0.1150389
Subject(s) - endometrium , mifepristone , stromal cell , endocrinology , medicine , follicular phase , progesterone receptor , biology , decidua , immunostaining , receptor , andrology , estrogen receptor , immunohistochemistry , pregnancy , placenta , fetus , cancer , breast cancer , genetics
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.