The effects of growth hormone on corpus luteum of superovulated rats.
In general, growth hormone acts as a factor promoting cell proliferation in the positive direction and suppresses apoptosis. No report has described growth hormone (GH)-induced structural luteolysis. The present studies showed that GH induced structural luteolysis in rats after the induction of functional luteolysis by treatment with bromocriptine, and that apoptotic cells were present among luteal cells during structural luteolysis as shown by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling. Zymography showed that the activity of matrix metalloproteinase (MMP)-2 increased during GH-induced structural luteolysis. The expression of c-myc protein of luteal cells was significantly decreased, but proliferating cell nuclear antigens (PCNA) were conversely increased during structural luteolysis, as shown by Western blot analysis. We propose that an excessive increase 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 catastrophe and inducing apoptosis in luteal cells, and that structural luteolysis may be triggered. GH-induced apoptosis in structural luteolysis therefore 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 destruction of extracellular matrix by MMP.
Kiya
T
T
Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, Japan.
Endo
T
T
Henmi
H
H
Goto
T
T
Kitajima
Y
Y
Manase
K
K
Takahashi
S
S
Kudo
R
R
D004092:20-alpha-Dihydroprogesterone / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001971:Bromocriptine / Q000494:pharmacology; D003338:Corpus Luteum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D018093:Gelatinases / Q000378:metabolism; D019382:Human Growth Hormone / Q000494:pharmacology*; D006801:Humans; D003341:Luteolysis / Q000097:blood / Q000187:drug effects / Q000378:metabolism; D020778:Matrix Metalloproteinase 2; D008666:Metalloendopeptidases / Q000378:metabolism; D008970:Molecular Weight; D009929:Organ Size / Q000187:drug effects; D011374:Progesterone / Q000097:blood; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013480:Superovulation
D018809:Proliferating Cell Nuclear Antigen; D016271:Proto-Oncogene Proteins c-myc; D019382:Human Growth Hormone; D004092:20-alpha-Dihydroprogesterone; D001971:Bromocriptine; D011374:Progesterone; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2