Regulation of bcl-2 gene family members in human endometrium by antiprogestin administration in vivo

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, Bar and oestrogen receptor proteins in secretory endometrium collected from ten patients with normal o vulatory cycles 4 or 6 days after the LH surge, and on the same days in a s ubsequent cycle in which the formation of secretory changes was inhibited b y the administration of the antiprogestin mifepristone (RU486) 2 days after the onset of the LH surge. Since some stromal cells display positive immun oreactivity, leucocyte subpopulations of macrophages (CD68-positive) and la rge granular lymphocytes (CD56-positive) were identified in serial sections . After administration of mifepristone on day 2 after the LH surge, a signi ficant increase in bcl2 immunoreactivity was observed in glandular and surf ace epithelium. A positive correlation (0.874) with nuclear oestrogen recep tor immunoreactivity in endometrial glands was demonstrated. Subsets of str omal cells, identified as CD68-positive macrophages and CD56-positive large granular lymphocytes displayed positive immunoreactivity for the bcl-2 epi tope, which was unaffected by mifepristone administration. Bar immunostaini ng was similar in control and antiprogestin-treated endometrium. These data indicate that antiprogestin administration inhibits progesterone downregul ation of steroid receptors in endometrial glands, resulting in persistence of a proliferative endometrium and accompanying bcl-2 secretion.