Identical changes in Bax expression, but not Fas ligand expression, occur in structural luteolysis in gonadotropin releasing hormone agonist- and prolactin-treated superovulated rats.
Structural luteolysis induced by gonadotropin releasing hormone agonist (GnRHa) or prolactin (PRL) is defined as histological involution of the corpus luteum. We reported that one of the mechanisms of structural luteolysis induced by PRL was tissue remodeling by matrix metalloproteinase (MMP) and also apoptosis in superovulated rats. We also reported that GnRHa induced structural luteolysis with elevation of MMP. In this study, we investigated whether GnRHa caused apoptosis in mature corpus luteum of superovulated rats and also examined the expression of apoptosis-related molecules (Fas, Fas ligand (FasL), Bcl-2, Bax). We gave 4-day GnRHa treatment 5 days after hCG injection to immature female rats treated with pregnant mare surum gonadotrophin (PMSG) and hCG to induce structural involution of mature corpus luteum. PMSG-hCG-treated rats without GnRHa treatment, rats treated with bromocryptine (Brom) to induce functional luteolysis and rats treated with Brom followed by PRL (Brom+PRL) to mimic the PRL surge to induce structural luteolysis as we previously reported were used for comparison. GnRHa treatment caused structural luteolysis characterized by structural involution, a decrease in the serum progestin level, and apoptotic bodies as well as structural luteolysis induced by Brom+PRL. FasL expression in corpora lutea was elevated after Brom treatment, but there was no elevation of FasL after GnRHa treatment started. FasL expression decreased and Bax expression increased in structural luteolysis induced by GnRHa as well as Brom+PRL treatment, although Fas and Bcl-2 expression did not change throughout the luteal phase. In summary, both GnRHa and Brom+PRL caused structural luteolysis, one of whose mechanisms was apoptosis with an increase in Bax expression, but not with an identical change in FasL expression. It is speculated that the significance in alteration of FasL may involve some mechanism other than apoptosis.
Endo
Toshiaki
T
Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, South 1 West 16, Chuo-ku, Sapporo 060-8543, Japan. endot@sapmed.ac.jp
Kiya
Tamotsu
T
Kitajima
Yoshimitsu
Y
Honnma
Hiroyuki
H
Chida
Manabu
M
Hayashi
Takumi
T
Henmi
Hirofumi
H
Yamazaki
Kiyohiro
K
Hayashi
Takuhiro
T
Manase
Kengo
K
Kudo
Ryuichi
R
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001971:Bromocriptine / Q000494:pharmacology; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D053222:Fas Ligand Protein; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D019254:Genes, bcl-2 / Q000235:genetics; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D006064:Gonadotropins, Equine / Q000494:pharmacology; D006801:Humans; D003341:Luteolysis / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D011372:Progestins / Q000097:blood; D011388:Prolactin / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D051381:Rats; D013480:Superovulation / Q000502:physiology*; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; C494828:Bax protein, rat; D006063:Chorionic Gonadotropin; D018491:Dopamine Agonists; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D006064:Gonadotropins, Equine; D008562:Membrane Glycoproteins; D011372:Progestins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D007987:Gonadotropin-Releasing Hormone; D001971:Bromocriptine; D011388:Prolactin