성 hormone이 rat 자궁 발달에 미치는 영향에 대한 proliferating cell nuclear antigen 항체의 면역조직학적 응용

고필옥,곽수동,Koh, Phil-ok,Kwak, Soo-dong 대한수의학회 1997 大韓獸醫學會誌 Vol.37 No.2

The study was designed to investigate the effects of progesterone and estrogen on the uterus of rats by immunohistochemical methods using Proliferating Cell Nuclear Antigen (PCNA) antibody. Eighteen female rats(Wistar), weighing initially about 300g, were ovariectomized. These rats were divided into four groups, progesterone-treated group, estrogen-treated group, estrogen+progesterone-treated group, and control group, progesterone-treated group was injected with 1mg of progesterone per rat per day for 2 days and estrogen-treated group with $20{\mu}g$ of $17{\beta}-estradiol$ for 3 days and estrogen+progesterone-treated group with $17{\beta}-estrdiol$ for 3 days and then with progesterone for 2 days as above. In gross findings, the uteri were markedly hypertrophied by estrogen treatment but were not affect in size by progesterone treatment. Immunohistochemical investigation was performed on the cell types with higher appearance of PCNA positive reaction cells in four groups. The groups with higher appearance of the stromal cells were ordered as estrogen-treated group, progesterone-treated group, estrogen+progesterone-treated group, and control group. The muscle cells were ordered as progesterone-treated group, estrogen-treated group, estrogen+progesterone-treated group, and control group. Positive reaction cells of the stromal cells were total 4.6 times higher than those of muscle cells. Therefore, the affect of the hypertrophy on the uterus by estrogen was larger than those of progesterone and affect on the uterus by stromal cells were larger than those of muscle cells. The group with more PCNA positive reaction cells of luminal epithelial cells were ordered as control group, progesterone-treated group, estrogen+progesterone-treated group, and estrogen-treated group, and glandular epithelial cells were ordered as estrogen+progesterone-treated group, progesterone-treated group, control group, and estrogen-treated group. It was suggested that estrogen and progesterone did not affect on the proliferating cells of luminal epithelial cells and affection of progesterone on the development of glandular epithelial cell was larger than that of estrogen.

Reproductive Responses of Awassi Ewes Treated with either Naturally Occurring Progesterone or Synthetic Progestagen

Husein, Mustafa Q.,Kridli, Rami T. Asian Australasian Association of Animal Productio 2002 Animal Bioscience Vol.15 No.9

The objective was to identify the appropriate form of progesterone, which exhibits compact reproductive responses in Awassi ewes during mid to late seasonal anestrous period. Forty-eight Awassi ewes were randomly allocated into four groups to be treated with 60 mg medroxyprogesterone acetate (MAP), 30 mg fluorogestone acetate (FGA), 40 mg FGA, or 600 mg progesterone sponges. After a 12 day period, sponges were removed and ewes were administered i.m. with 600 IU PMSG (d 0, 0 h). Five harnessed Awassi rams were turned-in with the ewes to detect heat. Ewes were checked for breeding marks at 6 h intervals for 5 days. Blood samples were collected from all ewes for analysis of progesterone concentrations. Pretreatment (d -13 and -12) progesterone concentrations were ${\leq}0.2ng/mL$ among all ewes and were indicative of seasonal anestrous period. On d 0, progesterone concentrations were elevated to $1.4{\pm}0.1ng/mL$ in ewes received progesterone sponges only and were higher (p<0.0001) than those (${\leq}0.2ng/mL$) administered MAP or FGA sponges. Progesterone concentrations returned to their basal values of <0.2 ng/mL within 24 h of sponge removal and were similar (p>0.1) among all ewes. Incidence of estrus was similar (p>0.1) among the four groups and occurred in 75% (9/12), 82% (9/11), 67% (8/12) and 58% (7/12) of the ewes receiving MAP, 30 mg FGA, 40 mg FGA and progesterone sponges, respectively. Estrous responses occurred 14.7, 20 and 13.6 h earlier in progesterone-sponge-treated ewes than those of MAP- (p<0.04), 30 mg FGA- (p<0.01) and 40 mg FGA-treated (p=0.06) ewes, respectively. Induced estrus conception rates were 50% (6/12), 55% (6/11), 50% (6/12) and 42% (5/12), out of which 4/6, 4/6, 3/6 and 3/5 lambed 151 days following d 0, and were similar (p>0.1) among ewes of the four treatment groups. Ewes that returned to estrus 16 to 20 days following d 0 were 5/12, 5/11, 6/12 and 4/12 ewes treated with MAP, 30 mg FGA, 40 mg FGA and progesterone sponges, respectively, and all lambed 169 days later. Overall lambing rates were 75% (9/12), 82% (9/11), 75% (9/12) and 58% (7/12) ewes treated with MAP, 30 mg FGA, 40 mg FGA and progesterone sponges, respectively. Results demonstrate that applications of MAP, 30 mg FGA, 40 mg FGA and progesterone sponges Awassi ewes were equally effective in induction of estrus and tended to favor both types of FGA and MAP in overall lambing rates over progesterone sponges during the seasonal anestrous period.

전립선 기질세포의 증식과 COX-2 발현에 대한 프로게스테론의 영향

정수련,김성한,최이화,박지은,전은미,강영진,이광윤,최형철 영남대학교 의과대학 2006 Yeungnam University Journal of Medicine Vol.23 No.1

전립선비대증은 노인 남성에서 흔히 유발되는 질환이며, 노화가 진행될 수록 빈도가 높아지는 특징을 가진다. 이 질환의 원인은 전립선기질세표의 과도한 증식으로 유발된다고 알려져 있지만 그 자세한 기전에 대해서는 잘 알려져 있지 않다. 전립선비대증에서 progesterone 수용체 양성 세포가 다른 전립선 종양에 비해서 많고, progesterone은 testosterone에서 DHT로 전환되는 것을 감소시키는 역할을 가진다고 알려졋다. 또한 남성 전립선 평활근의 과증식에 의한 질환이므로 평활근 세포의 증식과 관련성이 있다고 보고된 COX-2의 전립선비대증에 대한 영향에 대한 연구가 필요하다. 전립선 기질세포에 progesterone을 3일간 투여하여 배양한 경우 기질세포 증식은 차이가 없었다. Progesterone을 단독 또는 DHT와 같이 투여한 기질세포에서 남성호르몬 수용체 mRNA 발현은 비처리군과 비교하여 유의한 차이가 없었다. 또한 progesterone과 DHT 동시 투여에 의한 COX-2 mRNA 발현에도 차이가 없었다. 그러나 progesterone에 의한 남성 호르몬 수용체와 COX-2 단백 발현에서는 대조군과 비교하여 유의하게 감소시켰다. 이상의 결과는 progesterone은 남성호르몬 수용체에 대해 전사 후 반응 (post-transcriptional response)에 효과를 나타내어 남성호르몬 수용체 발현을 감소시키는 작용은 가지며, COX-2 발현 억제효과를 나타내므로 전립선비대증의 치료에 이용될 수 있을 것으로 사료된다. Background: Benign prostatic hyperplasia (BPH) is the most common benign tumor in older men; the etiology of this disease remains poorly understood. Testosterone and dihydrotestosterone (DHT) both act as androgen via a single androgen receptor. Testosterone is converted to DHT by 5α-reductase in prostatic stromal cells. Progesterone has been reported to inhibit DHT conversion; howevwe, its effect on prostatic stromal cells remains to be elucidated. Materials and Methods: In this experiment, we investigated the effect of progesterone on androgen receptor expression induced by DHT. We also tested the effect of progesterone on cyclooxygenase-2 (COX-2) expression, as well as prostate stromal cell proliferation using the cell count kit-8. Results: Progesterone did not cause an increase of prostate stromal cell proliferation. The mRNA expression of the androgen receptor and COX-2 were not changed by progesterone; the expressions of androgen receptor and COX-2 proteins were decreased by progesterone in prostate stromal cells. Conclusion: These results suggest that in prostate stromal cells, progesterone decreases androgen receptor protein expression, which results in decrement of COX-2 protein expression. This effect might be mediated by post-transcriptional regulation.

Molecular Mechanism of Progesterone-Induced Apoptosis in Human Breast Cancer T47D Cells

임지영,김태형,이영준,김인영,곽성준,이병무,명창순,김형식 대한암예방학회 2008 Journal of cancer prevention Vol.13 No.3

Progesterone plays an essential role in the development and differentiation of the mammary gland. Although it is well established that progesterone regulates cellular proliferation and differentiation, the molecular mechanisms of progesterone-mediated anticancer effects remain unclear. Therefore, the aim of the present study was to determine how progesterone regulates the growth and viability of T47D human breast cancer cells. In this study, the proliferation of T47D cells was inhibited after 48 hours of incubation in the presence of 10μM progesterone. The progesterone-treated T47D cells also exhibited hallmarks of apoptosis including DNA fragmentation and nuclear morphological changes detected with DAPI staining. Also, PR-A and PR-B progesterone receptor expression was decreased in a dose-dependent manner. Moreover, progesterone significantly decreased the expression of p53, cyclin D1, and CDK4, while it increased the expression of p27. These results clearly demonstrate high doses of progesterone induce T47D human breast cancer cell apoptosis and suppress proliferation by inhibiting the expression of key cell cycle regulators. (Cancer Prev Res 13, 177-183, 2008)

젖소 동결수정란의 비외과적 이식시 수란우의 혈장 progesterone, estradiol-17β치 및 혈청화학치가 수태율에 미치는 영향

이병천,조충호,황우석,Lee, Byeong-cheon,Jo, Choong-ho,Hwang, Woo-suk 대한수의학회 1989 大韓獸醫學會誌 Vol.29 No.4

A total of 13 synchronized dairy cattle(Holstein) were used to determine pregnancy rates in relation to plasma progesterone, estradiol-$17{\beta}$ levels and serum chemical values on the day of last $PGF_{2{\alpha}}$ injection and day of frozen/thawed bovine embryo transfer. The pregnancy rate of recipients with 1.0~4.0ng/ml of progesterone levels at the day of last $PGF_{2{\alpha}}$ injection was higher than that of recipients with below 1.0ng/ml or above 4.0ng/ml of progesterone levels. On the day of transfer, optimal progesterone levels were between 1.0ng/ml and 4.0ng/ml coinciding with a pregnancy rate of 88.9%. Pregnancy rate decreased when progesterone levels were below 1.0ng/ml(33.3%) or above 4.0ng/ml(0%). Corpus luteum grade did not affect pregnancy rate and this result revealed that manual palpation of corpus luteum was not valid criterion of corpus luteum function. Progesterone levels as well as pregnancy rate did not significantly differ whether the corpus luteum was on the right($1.62{\pm}1.33ng/ml$; 63.5%) or left ovary($1.99{\pm}0.61ng/ml$; 85.0%). Estradiol-$17{\beta}$ levels were not significantly different between pregnant and nonpregnant recipients, but estradiol-$17{\beta}$ levels($82.2{\pm}13.5$ VS. $72.3{\pm}10.1pg/ml$) were higher at below 1.0ng/ml of progesterone, and pregnancy rates(33.3 VS. 80%) tended to be lower than above 1.0ng/ml of progesterone. Total cholesterol levels on the day of last $PGF_{2{\alpha}}$ injection and day of transfer did not affect pregnancy rate. Calcium and inorganic phoshorus levels belonged to normal range in most of the recipients. These range did not affect pregnancy rate. In reviewing above results, plasma progesterone levels(1.0~4.0ng/ml) at the time of transfer are diagnostic value for screening recipients prior to transfer of frozen/thawed bovine embryos.

랫드 간 Epoxide Hydrolase와 Glutathione S-Transferase 유전자 발현에 미치는 Progesterone의 효과

조주연(Joo Youn Cho),김상건(Sang Geon Kim) 대한약리학회 1996 대한약리학잡지 Vol.32 No.2

Previous studies have shown that glucocorticoid suppresses microsomal epoxide hydrolase(EH) gene expression and that EH expression is altered during pregnancy. The effects of progesterone on the expression of rat EH and certain glutathione S-transferase(GST) genes were examined in this study. Northern RNA blot analysis revealed that progesterone was effective in increasing hepatic EH mRNA levels at 12 h to 48 h after treatment with a maximal 9-fold increase being noted at 12 h time point. Nonetheless, multiple daily treatment with progesterone rather caused minimal relative increases in EH mRNA levels. GST Ya and Yb1/2 mRNA levels were also transiently elevated at 12 h after progesterone treatment, followed by gradual decreases from the maximal Increases at day 1, 2 and 5 post-treatment. These changes in EH and GST mRNA levels were noted only at a relatively high dose of progesterone. Furthermore, immunoblot analyses showed that rats treated with progesterone for 5 days failed to show EH or GST induction, indicating that progesterone-induced alterations in EH and GST mRNA levels do not reflect bona fide induction of the detoxifying enzymes. Concomitant progesterone treatment of rats with the known EH inducers including ketoconazole and clotrimazole failed to additively nor antagonistically alter EH mRNA levels. In contrast, dexamethasone substantially reduced ketoconazole- or clotrimazole-inducible EH expression. These results showed that progesterone stimulates the EH, GST Ya and Yb1/2 gene expression at early times followed by marked reduction in the RNA levels from the maximum after multiple treatment and that the changes in mRNA do not necessarily reflect induction of the proteins.

Emergences of LH Surge Affected by Different Progesterone Levels in Ovariectomized Goats

김승준 한국임상수의학회 2014 한국임상수의학회지 Vol.31 No.1

The purpose of the present study was to determine the priming effects of progesterone that affect theemergence of LH surge mode secretion by three different progesterone levels. In previous studies, we have shownthat LH surge occurred in follicular levels of progesterone, whereas there was no surge mode secretion of LH andFSH in either the subluteal or luteal levels of progesterone. In this study, the hypothesis was that the priming effectsof progesterone on the timing of the LH surge induced by exogenous estradiol are same between subluteal and luteallevels of progesterone. Long-term ovariectomized Shiba goats that had received implants of estradiol capsules (Day0) and three different progesterone silastic packet inducing follicular, subluteal and luteal levels of progesterone weredivided into three groups such as non-P, low-P and high-P group. Blood samples were collected daily throughout theexperiment for the analysis of gonadal steroid hormone levels. On Day 7, all devices of progesterone packets wereremoved but estradiol capsules were maintained during the experiment, and blood samples were collected at 1 hr intervalfor 12 h from the time of progesterone removals to determine peripheral changes of estradiol and progesteroneconcentration. Then all animals were infused estradiol on the Day 7 after 13 h from the removals of progesteronedevices with a peristaltic pump into jugular vein at a rate of 3 μg/h for 36 h. For analysis of peripheral LH and estradiolconcentration, blood samples were collected via another jugular vein at 2 h intervals for 52 h (from 4 h before thestart of estradiol infusion to 48 h after the start of estradiol infusion). In all animals of the three groups treated withestradiol infusion, an LH surge was expressed but the peak time of LH surge was different. This time interval fromestradiol infusion until the peak of LH surge was gradually and significantly extended by the different levels ofprogesterone treated before estradiol infusions in the three groups.

Patterns of Pulsatile and Surge Modes of Follicle-Stimulating Hormone Treated with Different Progesterone Levels in Ovariectomized Goats

김승준,Tomomi Tanaka,Hideo Kamomae 한국임상수의학회 2011 한국임상수의학회지 Vol.28 No.2

The objective of the present study was to determine the progesterone levels that effects on the pulsatile and surge modes of FSH secretion. In previous studies we have shown that LH surge occurred in the follicular levels of progesterone, whereas there was no surge mode secretion of LH in either the subluteal or luteal levels of progesterone. LH pulsatile frequencies were high in two groups such as follicular level and subluteal level. But in the luteal level of progesterone the pulsatile pattern of LH were strongly suppressed. Namely, subluteal levels of progesterone, around 1 ng/ml, completely suppressed the LH surge but did not affect the pulsatile frequency of LH secretion. Because of this we hypothesized that the two secretory patterns of FSH are similar to that of LH. Long-term ovariectomized Shiba goats that had received implants of estradiol capsules and three different progesterone silastic packet inducing follicular, subluteal and luteal levels of progesterone were divided into three groups such as non-P, low-P and high-P group.Blood samples were collected daily throughout the experiment for the analysis of gonadal steroid hormone levels and at 10-min intervals for 8 h on Days 0, 3, and 7 (Day 0: just before progesterone treatment) for analysis of the pulsatile frequency of FSH secretion. Then estradiol was infused into the jugular vein of all animals at a rate of 3 μg/h for 16 h on Day 8 to determine whether an FSH surge was induced. Blood samples were collected every 2 h from 4h before the start of the estradiol infusion until 48 h after the start of the infusion. In each group, the mean ± SEM concentration after progesterone implant treatment was 3.3 ± 0.1 ng/ml for the high P group, 1.1 ± 0.1 ng/ml for the low P group, and < 0.1 ng/ml for the non-P group, concentrations similar to the luteal levels, subluteal levels, and follicular phase levels of the normal estrous cycle, respectively. The FSH pulse frequency was maintained highly in all groups on Day 0, Day 3 and Day 7. An FSH surge was induced in all 4 cases of the Non-P group. In the High P and Low P groups, the plasma concentrations of FSH remained low until 48 h after the start of estradiol infusion, and no occurrence of FSH surge was found in any of the animals. The results of this study not only confirm that the pulsatile patterns of FSH were not inhibited strongly relative to LH, they also suggest that some other mechanism and factor may be controlling the FSH secretion.

임신 및 비임신 가토 자궁수축에 대한 progesterone의 억제효과

송창훈,박석천,송형근,정혁,한세준 朝鮮大學校 附設 醫學硏究所 1995 The Medical Journal of Chosun University Vol.20 No.2

The effects of Progesterone on the uterus have been known to play a key role in parturition during the last three decades. But the exactly how progesterone effects the uterus has not been discovered completely . In these animal experiments, we searched for evidence of progesterone inhibitory effects on uterine contraction in the non-pregnant rabbit. We postulated that progesterone inhibits uterine contraction in the pregnant rabbit, but also non pregnant rabbit uterus. In this study, nonpregnant rabbit (n=4). pregnant rabbit (n=4), progesterone primed rabbit (n=4), oophorectomized rabbit (n=2). estrogenized rabbit (n=2) were selected for measuring the uterine contraction by a intrauterine balloon method. Uterine contractions were charted by polygraph, and the results were analyzed by Student t test. The results are as follows: 1. Spontaneous and regular uterine contraction were monitored in the nonpregnant rabbit. 2. In the pregnant rabbit(#17th day), irregular and inhibited uterine contracture was detected. 3. After 5 days of progesterone injection, uterine contractility decreased, exhibiting a similar pattern to that of the pregnant rabbit. 4. In the estrogenized rabbit, intense uterine contraction were detected. 5. In the oophorectomized rabbit, regular and spontaneous contraction were detected, but contractile force was less thanin the nonpregnant group. These results suggest that progesterone inhibits the uterine contractions in the rabbit, and estrogen stimulates the contraction. But these results suggest that progesterone is not the only suppressorof uterine muscle activity in the pregnant rabbit.

재래산양의 번식기에 있어서 혈중 Steroid Hormone 수준 변화에 관한 연구 III. 분만전후의 혈중 Progesterone 및 $20\alpha$-Dihydroprogesterone

민관식,장규태,오석두,성환후,이병오,윤창현 한국동물번식학회 1992 Reproductive & developmental biology Vol.16 No.2

The present study was conducted to find out the changes of progesterone and 20$\alpha$-dihydroprogesterone(20$\alpha$-OHP) levels before and after parturition, 4 pluriparous goats were offered for this experiment. Blood samples were taken from jugular vein on Days, 5, 3, 2 and 1 before parturition, the day of parturition, 1, 3, 5, 7 and 9 after parturition. The blood samples were centraifuged and stored at -2$0^{\circ}C$ until hormone assay. The serum levels of progesterone and 20$\alpha$-OHP were measrued by radioimmunoassay. The changes of serum progesterone level during peripartum period were characterized as a remarkable decrease. The progesterone level was 4.05$\pm$0.52ng/ml on 56 days before parturition and decreased to 2.24$\pm$0.38ng/ml on 1 day before parturition and 0.79$\pm$0.09ng/ml on the day of parturition and the basal level was maintained through 9 days of postpartum period. The serum level of 20$\alpha$-OHP during the peripartum period was 1.25$\pm$0.21ng/ml on 5 days before paturition and increased to 1.32$\pm$0.25 on 3 days and 1.59$\pm$0.24ng/ml on 1 day before parturition, and reached a peak level of 1.78$\pm$0.25ng/ml just prior to parturition and then decreased greatly to 0.31$\pm$0.03ng/ml on 1 day postpartum and the basal level was remained until 9 days postpartum. The high serum level of 20$\alpha$-OHP, which was peak just prior to parturition, was maintained for 2 days following the onset of remarkable decrease in the serum level of progesterone. From the above results, it was concluded that the enzyme 20$\alpha$-hydroxysteroid dehydrogenase (20$\alpha$-HSD) catalyzing the conversion of progesterone to a biologically inactive steroid, 20$\alpha$-OHP was active properly in the luteal cells in Korean native goats.