Apoptosis and PCNA Expression Induced by Prolactin in Structural Involution of the Rat Corpus Luteum

There are two stages of luteal regression. The first stage is functional regression that is characterized by a decreased production of progesterone secretion; the second stage of structural involution is referred to as a structural luteolysis. In rodents, prolactin has a biphasic action on the corpus luteum. It is luteotrophic, but when exposed to functionally regressed corpora lutea it causes luteolysis. The objective of the present studies was to examine mechanisms of prolactin action in structural luteolysis, whether apoptosis is involved in this process, and to examine the possible association of cell proliferation signals as mediators of structural luteolysis. Prolactin-induced structural luteolysis was associated with apoptosis verified by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL). Apoptotic cells made up about 3% of the cells 24 hours after the first injection of prolactin, a level that remained constant at all stages of structural luteolysis. Total ovarian weight and DNA content were decreased about 50% in 72 hours after induction of structural luteolysis by prolactin, The finding of about 3% of cells in apoptosis indicates apoptosis is a rapid process. Proliferating cell nuclear antigens (PCNA) of luteal cells were significantly decreased during functional luteal regression, but were conversely increased in structural luteolysis as shown by western blotting and immunohistochemistry. In general PCNA expression is reported to be decreased during structural involution, and there are no reports that have linked excess expression of PCNA with apoptosis and structural luteolysis. We speculate that an excessive increase in expression of PCNA which signals activation of cell proliferation creates a disorder in the signals involved with DNA synthesis. This disorder results in mitotic catastrophe and in the induction of apoptosis. Therefore the disorder of cell cycle signals in luteal cells are associated with prolactin induced apoptosis in structural luteolysis.