TERMINATION OF LACTATION INDUCES APOPTOSIS AND ALTERS THE EXPRESSION OF THE BCL-2 FAMILY MEMBERS IN THE RAT ANTERIOR-PITUITARY

After lactation, there is a massive loss of pituitary lactotrophs. The aim of this study was to investigate the events and mechanisms involv ed in the remodeling of the anterior pituitary after termination of la ctation. Animals were analyzed at day 7 of lactation and at 4 and 7 da ys after pup removal. Field-inversion gel electrophoresis was used to detect high-molecular-weight DNA fragments, a characteristic feature o f apoptosis. Bar and Bcl-2, proteins involved in regulation of cell su rvival, were studied by immunohistochemistry and Western blot analysis . In addition, the expression of Bar, Bcl-2, Bcl-X-L, and p53 messenge r RNA (mRNA) was analyzed by in situ hybridization. Four days after te rmination of lactation, a peak in high-molecular-weight DNA fragments and an increase in Bar, along with a decrease in Bcl-2 proteins, were observed, in comparison with lactation and with 7 days post lactation. The mRNAs for Bar and p53 also were increased, whereas no changes wer e detected in Bcl-2 and Bcl-X-L mRNA levels. In summary, these finding s indicate that the cell remodeling of the anterior pituitary, after t he termination of lactation, occurs through the process of apoptosis a nd involves changes in Bar, Bcl-2, and p53.