Role of Prostaglandin E in Modulating Immune Response in Lymph Nodes Draining the Uterus during the Implantation Period in Rats

조혜성,유경자,김창미,Cho, Hye-Seong,Ryu, Kyung-Za,Kim, Chang-Mee The Korean Society of Pharmacology 1989 대한약리학잡지 Vol.25 No.1

본 교실의 연구결과에 의하면 토끼와 흰쥐에서 수정란 착상시기에 peripheral lymphocyte와 thymocyte의 활성도가 저하될 뿐만 아니라 착상기간중 생성되는 prostaglandin E(PGE)의 생리적인 농도로도 peripheral lymphocyte와 thymocyte의 활성도가 억제되었다. 그러므로 본 연구에서는 흰쥐의 착상시기에 전신적인 면역기능 뿐만 아니라 국소적으로 DLN lymphocyte의 활성도가 억제되는지를 관찰하고 PGE가 어떠한 기전으로 모체의 면역기능을 억제하는가를 관찰하여 다음과 같은 결과를 얻었다. 1. 흰쥐의 착상시기에 DLN lymphocyte의 활성도가 임신하기 않은 흰쥐의 DLN lymphocyte에 비하여 통계적으로 유의하지는 않으나 저하되었으며 이러한 저하현상은 100% 흰쥐에서 관찰되었다. 2. 착상시기의 DLN lymphocyte에 prostaglandin 합성억제제인 indomethacin(ID)를 처리하면 DLN lymphocyte의 활성도가 통계적으로 유의하게 증가하였다. 그러나 임신하지 않은 흰쥐의 DLN lymphocyte의 활성도는 증가되어 있으나 $PGE_2$를 전처리하면 DLN lymphocyte의 활성도가 유의하게 억제되며 $PGE_2$를 전처치한 후 ID를 처리하면 DLN lymphocyte의 활성도가 $PGE_2$로 전처치하지 않고 ID를 처리한 경우에 비하여 유의하게 증가하였다. 그러나 $PGE_2$ 대신estradiol, progesterone 및 hCG를 전처치하였을 경우에는 ID 처리로 DLN lymphocyte의 활성도가 증가하지 않았다. 3. 임신하지 많은 흰쥐의 DLN lymphocyte에 $PGE_2$를 전처리하면 PGE-producing cell이 유도되어 PGE 생성이 증가하는지를 확인하기 위하여 $PGE_2$를 전처리하고 Con A를 처리한 후 배양액의 PGE를 정량한 결과 PGE를 전처리하지 않은 DLN lymphocyte에 비하여 유의하게 PGE 생성이 증가하였다. 이상의 결과로 보아 흰쥐의 착상시기에는 모체의 DLN lymphocyte의 활성도가 저하되며, 특히 PCE는 PGE-producing cell을 유도함으로써 착상시기의 모체의 면역기능에 영향을 주는 것으로 생각된다. In our previous studies, it was found that activities of maternal peripheral lymphocytes and thymocytes were depressed during the implantation period in rats and rabbits. This study was therefore attempted to clarify further this immunosuppression locally by determining lymphocyte response in lymph nodes draining the uterus (DLN) and to elucidate the mechanism by which prostaglandin E (PGE) modulates immune response during the implantation process in rats. As compared with non-pregnant rats, the response of DLN lymphocytes to concanavalin A (Con A) was depressed during the implantation period in 100% of rats studied. The activity of DLN lymphocytes depressed on day 8 of pregnancy was, however, restored partially by the treatment of indomethacin (ID), indicating that prostaglandin (PG) might be one of factors responsible for immunomodulation during the process of implantation. DLN lymphocyte activity in non-pregnant rats was suppressed if PGE was pre-treated prior to Con A and this suppression was partially restored by the treatment of ID. Furthermore, DLN lymphocytes pre-treated with PGE produced PGE in vitro and this PGE production was blocked by the treatment of ID, suggesting that PGE induced PGE-producing cells. However, the pretreatment of estradiol, progesterone, and hCG at doses enough to suppress lymphocyte activity was ineffective in inducing PGE-producing cells. From these results, it is suggested that PGE induces PGE-producing suppressor cells, thereby increasing PGE concentration and PGE in turn depresses maternal local immune response as well as systemic immune response during the implantation period in rats.

Depression of Maternal Immune Response during the Period of Implantation in Rabbits

조혜성,유경자,홍사석,Cho, Hye-Seong,Ryu, Kyung-Za,Hong, Sa-Suk The Korean Society of Pharmacology 1987 대한약리학잡지 Vol.23 No.2

본 실험에서는 가토에서 배반포가 자궁내막에 착상할 때, 모체의 면역기능의 변화를 알아보고, 착상시 관여하는 호르몬과 모체의 면역기능과의 연관성을 관찰하여 다음과 같은 결과를 얻었다. 1. 임신 7일째 가토의 말초혈관 림프구에 concanavalin A를 처리하면, 임신하지 않은 가토의 림프구보다 훨씬 낮은 자극지수를 나타냄으로써 면역억제 현상이 나타나는 것을 관찰할 수 있었다. 2. 임신 7일 때의 혈청 progesterone농도인 11.56 ng/ml을 임신하지 않는 가토의 말초혈관 림프구에 처리하면, 억제현상을 나타내지 않았으나, Progesterone의 농도가 1000 ng/ml 이상에서는 농도에 비례하여 림프구의 활성도가 감소되었다. 3. 4.5 ng/ml${\sim}$4,500 ng/ml의 $PGF_{2{\alpha}}$는 concanavalin A처리시 림프구의 활성도에 별다른 영향을 끼치지 않았으나, PGE는 4.5 ng/ml${\sim}$4,500 ng/ml에서 농도에 비례하여 림프구의 활성도를 유의하게 감소시켰다. 그러나 임신 제 8일째의 말초혈관 림프구에 prostaglandin 합성 억제제인 indomethacin 0.1 또는 $1\;{\mu}g/ml$을 처리하면 억제되었던 림프구 활성도가 각각28%, 23% 증가되었다. 이상의 결과로 보아 토끼의 착상기간중 모체의 면역기능이 저하되며 PGE가 착상기간중 면역기능을 저하시키는 요소중 하나인 것으로 생각된다. We determined the maternal peripheral lymphocyte response to mitogen during the period of implantation and evaluated the effects of hormones, which are known to be involved in the process of implantation, on the lymphocyte activity in rabbits. As compared with peripheral lymphocyte activity in non-pregnant rabbits, lymphocyte activity was significantly depressed on days 6, 7 and 9 of pregnancy. Although concentrations of serum progesterone were gradually increased during the implantation period, progesterone did not inhibit lymphocyte activity at physiological concentration. Serum $PGF_{2{\alpha}}$ was significantly increased on day 7 while PGE was slightly increased. $PGF_{2{\alpha}}$ did not modify lymphocyte activity even with greater concentrations than physiological level. However, lymphocyte activity was significantly inhibited by PGE even with physiological doses. The treatment of indomethacin at doses of 0.1 or $1.0\;{\mu}g/ml$ tended to enhance lymphocyte response, which was depressed on day 8 of pregnancy, 28% or 23% respectively. Although in non-pregnant rabbit, enhancement of lymphocyte response was also shown after the treatment of indomethacin, this enhancement was much less than that in pregnant rabbits. These results strongly suggest that maternal immune response was depressed during the process of implantation and PGE might be one of factors for immunomodulation during this period.

토끼의 착상기간 중 모체의 면역 억제 현상에 관한 연구

조혜성(Hye-seong Cho),유경자(Kyung-za Ryu),홍사석(Sa-Suk Hong) 대한약리학회 1987 대한약리학잡지 Vol.23 No.2

본 실험에서는 가토에서 배반포가 자궁내막에 착상할 때, 모체의 면역기능의 변화를 알아보고, 착상시 관여하는 호르몬과 모체의 면역기능과의 연관성을 관찰하여 다음과 같은 결과를 얻었다. 1. 임신 7일째 가토의 말초혈관 림프구에 concanavalin A를 처리하면, 임신하지 않은 가토의 림프구보다 훨씬 낮은 자극지수를 나타냄으로써 면역억제 현상이 나타나는 것을 관찰할 수 있었다. 2. 임신 7일 때의 혈청 progesterone농도인 11.56 ng/ml을 임신하지 않는 가토의 말초혈관 림프구에 처리하면, 억제현상을 나타내지 않았으나, Progesterone의 농도가 1000 ng/ml 이상에서는 농도에 비례하여 림프구의 활성도가 감소되었다. 3. 4.5 ng/ml~4,500 ng/ml의 PGE_2α는 concanavalin A처리시 림프구의 활성도에 별다른 영향을 끼치지 않았으나, PGE는 4.5 ng/ml~4,500 ng/ml에서 농도에 비례하여 림프구의 활성도를 유의하게 감소시켰다. 그러나 임신 제 8일째의 말초혈관 림프구에 prostaglandin 합성 억제제인 indomethacin 0.1 또는 1μg/ml을 처리하면 억제되었던 림프구 활성도가 각각28%, 23% 증가되었다. 이상의 결과로 보아 토끼의 착상기간중 모체의 면역기능이 저하되며 PGE가 착상기간중 면역기능을 저하시키는 요소중 하나인 것으로 생각된다. We determined the maternal peripheral lymphocyte response to mitogen during the period of implantation and evaluated the effects of hormones, which are known to be involved in the process of implantation, on the lymphocyte activity in rabbits. As compared with peripheral lymphocyte activity in non-pregnant rabbits, lymphocyte activity was significantly depressed on days 6, 7 and 9 of pregnancy. Although concentrations of serum progesterone were gradually increased during the implantation period, progesterone did not inhibit lymphocyte activity at physiological concentration. Serum PGE_2α was significantly increased on day 7 while PGE was slightly increased. PGE_2α did not modify lymphocyte activity even with greater concentrations than physiological level. However, lymphocyte activity was significantly inhibited by PGE even with physiological doses. The treatment of indomethacin at doses of 0.1 or 1.0μg/ml tended to enhance lymphocyte response, which was depressed on day 8 of pregnancy, 28% or 23% respectively. Although in non-pregnant rabbit, enhancement of lymphocyte response was also shown after the treatment of indomethacin, this enhancement was much less than that in pregnant rabbits. These results strongly suggest that maternal immune response was depressed during the process of implantation and PGE might be one of factors for immunomodulation during this period.

흰쥐의 착상기간 중 DLN(lymph nodes draining the uterus) Lymphocyte의 활성도에 미치는 Prostaglandin E의 영향

조혜성(Hye-seong Cho),유경자(Kyung-za Ryu),김창미(Chang-mee Kim) 대한약리학회 1989 대한약리학잡지 Vol.25 No.1

본 교실의 연구결과에 의하면 토끼와 흰쥐에서 수정란 착상시기에 peripheral lymphocyte와 thymocyte의 활성도가 저하될 뿐만 아니라 착상기간중 생성되는 prostaglandin E(PGE)의 생리적인 농도로도 peripheral lymphocyte와 thymocyte의 활성도가 억제되었다. 그러므로 본 연구에서는 흰쥐의 착상시기에 전신적인 면역기능 뿐만 아니라 국소적으로 DLN lymphocyte의 활성도가 억제되는지를 관찰하고 PGE가 어떠한 기전으로 모체의 면역기능을 억제하는가를 관찰하여 다음과 같은 결과를 얻었다. 1. 흰쥐의 착상시기에 DLN lymphocyte의 활성도가 임신하기 않은 흰쥐의 DLN lymphocyte에 비하여 통계적으로 유의하지는 않으나 저하되었으며 이러한 저하현상은 100% 흰쥐에서 관찰되었다. 2. 착상시기의 DLN lymphocyte에 prostaglandin 합성억제제인 indomethacin(ID)를 처리하면 DLN lymphocyte의 활성도가 통계적으로 유의하게 증가하였다. 그러나 임신하지 않은 흰쥐의 DLN lymphocyte의 활성도는 증가되어 있으나 PGE₂를 전처리하면 DLN lymphocyte의 활성도가 유의하게 억제되며 PGE₂를 전처치한 후 ID를 처리하면 DLN lymphocyte의 활성도가 PGE₂로 전처치하지 않고 ID를 처리한 경우에 비하여 유의하게 증가하였다. 그러나 PGE₂ 대신estradiol, progesterone 및 hCG를 전처치하였을 경우에는 ID 처리로 DLN lymphocyte의 활성도가 증가하지 않았다. 3. 임신하지 많은 흰쥐의 DLN lymphocyte에 PGE₂를 전처리하면 PGE-producing cell이 유도되어 PGE 생성이 증가하는지를 확인하기 위하여 PGE₂를 전처리하고 Con A를 처리한 후 배양액의 PGE를 정량한 결과 PGE를 전처리하지 않은 DLN lymphocyte에 비하여 유의하게 PGE 생성이 증가하였다. 이상의 결과로 보아 흰쥐의 착상시기에는 모체의 DLN lymphocyte의 활성도가 저하되며, 특히 PCE는 PGE-producing cell을 유도함으로써 착상시기의 모체의 면역기능에 영향을 주는 것으로 생각된다. In our previous studies, it was found that activities of maternal peripheral lymphocytes and thymocytes were depressed during the implantation period in rats and rabbits. This study was therefore attempted to clarify further this immunosuppression locally by determining lymphocyte response in lymph nodes draining the uterus (DLN) and to elucidate the mechanism by which prostaglandin E (PGE) modulates immune response during the implantation process in rats. As compared with non-pregnant rats, the response of DLN lymphocytes to concanavalin A (Con A) was depressed during the implantation period in 100% of rats studied. The activity of DLN lymphocytes depressed on day 8 of pregnancy was, however, restored partially by the treatment of indomethacin (ID), indicating that prostaglandin (PG) might be one of factors responsible for immunomodulation during the process of implantation. DLN lymphocyte activity in non-pregnant rats was suppressed if PGE was pre-treated prior to Con A and this suppression was partially restored by the treatment of ID. Furthermore, DLN lymphocytes pre-treated with PGE produced PGE in vitro and this PGE production was blocked by the treatment of ID, suggesting that PGE induced PGE-producing cells. However, the pretreatment of estradiol, progesterone, and hCG at doses enough to suppress lymphocyte activity was ineffective in inducing PGE-producing cells. From these results, it is suggested that PGE induces PGE-producing suppressor cells, thereby increasing PGE concentration and PGE in turn depresses maternal local immune response as well as systemic immune response during the implantation period in rats.

노지 및 무가온하우스에서 몇가지 비파품종의 수확시기 및 과실특성

박문영(Moon Young Park),조윤섭(Youn Seop Jo),박재옥(Jae Ok Park),조혜성(Hye Seong Cho),방극필(Geuk Pil Bang),고갑천(Gab Cheon Koh) 한국원예학회 2007 한국원예학회 학술발표요지 Vol.2007 No.6

비파의 적과시기 및 방법

박문영(Moon Young Park),조윤섭(Youn Seop Jo),박재옥(Jae Ok Park),조혜성(Hye Seong Cho),방극필(Geuk Pil Bang),박용서(Yong Seo Park) 한국원예학회 2007 한국원예학회 학술발표요지 Vol.2007 No.6

토끼의 착상기간중 난소홀몬과 난소홀몬 수용체에 관한 연구

윤미정,유경자,조혜성 대한내분비학회 1987 Endocrinology and metabolism Vol.2 No.2

The present study was undertaken to understand the mechanism by which implantation takes place by determining progesterone and estradiol concentrations in serum and their receptors in uterine tissues, thereby correlating hormone levels with their receptor numbers, during the implantation period in rabbits. The results obtained were as follows. 1) Serum estradiol concentrations were not changed from days 1 to 12 whereas progesterone levels were gradually increased, reachingg the maximum on day 7. 2) Kds for cytosolic and nuclear estrogen receptors were 0.41 nM and 0.26 nM while Kds for cytosolic and nuclear progesterone receptors were 1.23 nM and 0.63 nM in uterine tissues on days 6-8. 3) Concentrations of cytosolic and nuclear estrogen receptors and cytosolic progesterone receptor were decreased on days 6-8 compared to those from nonpregnant rabbits whereas nuclear progesterone receptor levels were slightly increased. 4) Cytosolic estrogen receptor levels in the implant sites were lower than those in the non-implant sites whereas nuclear estrogen receptor levels in the implant sites were greater than those in the non-implant sites. It is, therefore, concluded that concentrations of steroid receptors in uterine tissues as well as estradiol and progesterone in serum were changed during the implantation period in rabbits.

흰쥐 자궁의 Estrogen 수용체에 관한 연구

박찬규,최동희,유경자,조혜성,이건수 대한내분비학회 1986 Endocrinology and metabolism Vol.1 No.2

Estrogen receptor is a very unstable regulatory protein and can be easily influenced by various assay conditions. This study was attempted to determine optimal conditions for the ligand and receptor interaction, thereby establishing a stable and reliable estrogen assay system with rat uterus. 1) For the separation of bound and free forms after incubation of cytosolic ER and radioligand, it was found to be optimal that reaction mixture was incubated sith dextran-coated charcoal for 20 min. 2) Specific binding of cytosolic ER was stable when cytosolic ER was incubated with radioligand at 4℃ for 24 hrs while maximum specific bining was prominent when incubated at 30℃ for 1 hr. 3) Suitable cytosolic protein conc. For incubation was between 2 and 3 mg/ml. 4) By employing above assay conditions, Kd of uterine cytosolic ER in vitro was 0.12 nM. 5) Concentrations of endogenous estradiol during estrus cycle of rats did not interfere with specific binding of cytosolic ER. 6) 3 times-washing of nuclear ER incubates gaveise to best result in separationg bound and free forms. 7) Optimal binding was obtained when nuclear ER was incubated with ³H-estradiol at 30℃ for 1hr and Kd of nuclear ER was 0.9 nM.