In general, growth hormone acts as a factor promoting cell proliferation in
the positive direction and suppresses apoptosis. No report has described g
rowth hormone (GH)-induced structural luteolysis. The present studies showe
d that GH induced structural luteolysis in rats after the induction of func
tional luteolysis by treatment with bromocriptine, and that apoptotic cells
were present among luteal cells during structural luteolysis as shown by t
erminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling
. Zymography showed that the activity of matrix metalloproteinase (MMP)-2 i
ncreased during GH-induced structural luteolysis. The expression of c-myc p
rotein of luteal cells was significantly decreased, but proliferating cell
nuclear antigens (PCNA) were conversely increased during structural luteoly
sis, as shown by Western blot analysis. We propose that an excessive increa
se in PCNA and a marked decrease in c-myc protein of luteal cells lead to a
disorder in the signals concerned with DNA synthesis, causing mitotic cata
strophe and inducing apoptosis in luteal cells, and that structural luteoly
sis may be triggered. GH-induced apoptosis in structural luteolysis therefo
re highly depends on the cell cycle. There are thought to be two mechanisms
of GH-induced structural luteolysis. One is apoptosis, and the other is de
struction of extracellular matrix by MMP.