TY - JOUR
T1 - Potential role of hCG in apoptosis of human luteinized granulosa cells
AU - Hirata, Rei
AU - Hojo, Takuo
AU - Sano, Masahiro
AU - Hayashi, Nobuyoshi
AU - Okuda, Kiyoshi
N1 - Publisher Copyright:
© 2015 by the Society for Reproduction and Development.
PY - 2015
Y1 - 2015
N2 - The corpus luteum (CL) forms after ovulation and acts as a temporary endocrine gland that produces progesterone (P4), a hormone that is essential for implantation and maintenance of pregnancy in mammals. In pregnant women, human chorionic gonadotropin (hCG) secreted by the conceptus prevents luteolysis. hCG also increases the survival of cultured human luteinized granulosa cells (hLGCs). To clarify the maintenance mechanism of the human CL, we investigated the effects of hCG and P4 receptor antagonists, onapristone (OP) and RU486, on the viability of hLGCs. With the patients’ consent, hLGCs were isolated from follicular aspirates for in vitro fertilization. The cells were cultured with hCG (0.1, 1, 10, 100 IU/ml), OP (10, 25, 50, 100 μM), RU486 (100 μM), P4 (1, 10, 25, 50 μM) or some combination of the four for 24 h. Cell viability was significantly increased by hCG (100 IU/ml) and significantly decreased by OP (100 μM) compared with the control. Cells treated with hCG and OP together were significantly less viable than the control and OP-treated cells. The combined treatment also significantly increased CASP3 activity and cleaved CASP3 protein expression. Furthermore, P4 addition reversed the reduction in cell viability caused by the combination of hCG and OP treatment. The overall findings suggest that hCG cooperates with P4 to increase survival of hLGCs and to induce apoptosis when P4 action supported by hCG is attenuated in the human CL.
AB - The corpus luteum (CL) forms after ovulation and acts as a temporary endocrine gland that produces progesterone (P4), a hormone that is essential for implantation and maintenance of pregnancy in mammals. In pregnant women, human chorionic gonadotropin (hCG) secreted by the conceptus prevents luteolysis. hCG also increases the survival of cultured human luteinized granulosa cells (hLGCs). To clarify the maintenance mechanism of the human CL, we investigated the effects of hCG and P4 receptor antagonists, onapristone (OP) and RU486, on the viability of hLGCs. With the patients’ consent, hLGCs were isolated from follicular aspirates for in vitro fertilization. The cells were cultured with hCG (0.1, 1, 10, 100 IU/ml), OP (10, 25, 50, 100 μM), RU486 (100 μM), P4 (1, 10, 25, 50 μM) or some combination of the four for 24 h. Cell viability was significantly increased by hCG (100 IU/ml) and significantly decreased by OP (100 μM) compared with the control. Cells treated with hCG and OP together were significantly less viable than the control and OP-treated cells. The combined treatment also significantly increased CASP3 activity and cleaved CASP3 protein expression. Furthermore, P4 addition reversed the reduction in cell viability caused by the combination of hCG and OP treatment. The overall findings suggest that hCG cooperates with P4 to increase survival of hLGCs and to induce apoptosis when P4 action supported by hCG is attenuated in the human CL.
KW - Human chorionic gonadotropin
KW - Human luteinized granulosa cell
KW - Progesterone
KW - Survival factor
UR - http://www.scopus.com/inward/record.url?scp=84923382701&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84923382701&partnerID=8YFLogxK
U2 - 10.1262/jrd.2014-115
DO - 10.1262/jrd.2014-115
M3 - Article
C2 - 25451535
AN - SCOPUS:84923382701
VL - 61
SP - 67
EP - 73
JO - Journal of Reproduction and Development
JF - Journal of Reproduction and Development
SN - 0916-8818
IS - 1
ER -