MEK/ERK signaling pathway regulates the expression of Bcl-2, Bcl-XL, and Mcl-1 and promotes survival of human pancreatic cancer cells

Abstract

In this study, we used a rat model to investigate the effects of gonad hormones and replacement therapy on bone structure and the immune system. In the first phase of the study, 3- and 11-month-old F344 rats underwent ovariectomy (OVX) or were sham operated. Three months later, severe osteopenia was histologically observed in OVX rats of both age groups. The changes in the bone marrow structure of OVX rats included deterioration of cancellous bone that was associated with a remarkable increase of adipocyte cells. Furthermore, differential analyses for the expression of cell surface antigens by lymph-myeloid cells was studied using flow cytometry (FACS). The number of myeloid cells expressing ED-9(+) or CD-44(+) was similar in both age groups, and unaffected by OVX. However, an augmentation of T-lymphoid cells expressing CD4(+), CD5(+), or both, were observed with age, as well as after OVX. In the second phase of the study, 11-month-old rats were divided into five experimental groups: sham-operated, OVX, and OVX treated with sustained-release pellets of 17beta-estradiol (OVX-E), progesterone (OVX-P), or both (OVX-E/P). Hormone replacement therapy maintained low physiological levels, and rats were tested 12 weeks after treatment initiation. Administration of 17beta-E, with or without the addition of progesterone, prevented the rise of T lymphoid cells observed in OVX rats, whereas progesterone alone had no effect. In agreement with findings from the first phase, neither OVX nor replacement therapy affected the myeloid cells expression of ED-9 or CD-44. In summary, the cellular changes in the bone marrow of OVX rats were associated with an increase in adipocytes that was correlated with bone atrophy. An augmentation of T-lymphopoiesis was noted with increase in age or after OVX. This increase was reversed to baseline levels by 17beta-E treatment.