• 대한약리학회지
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• 제23권2호
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• pp.57-75
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• 1987

Two modalities of gonadotropin secretion, pulsatile gonadotropin and preovulatory gonadotropin surge, have been identified in the mammals. Pulsatile gonadotropin secretion is modulated by the pulsatile pattern of GnRH release and complex ovarian steroid feedback actions. The neural mechansim that regulates the pulsatile release of GnRH in the hypothalamus is called "GnRH pulse generator". Ovarian steroids, estradiol and progesterone, appear to exert thier feedback effects both directly on the pituitary to modulate gonadotropin release and on a hypothalamic site to modulate GnRH release; estradiol primarily affects the amplitude while progesterone decreases the frequency of the pulsatile GnRH. Steroid hormones are known to affect catecholamine transmission in brain. MBH-POA is richly innervated by NE systems and close apposition of NE terminals and GnRH cell bodies occurs in the MBH as well as in the POA. NE normally facilitates pulsatile LH release by acting through ${\alpha}-receptor$ mechanism. However, precise nature of facilitative role of NE transmission in maintaining pulsatile LH has not been clearly understood. Close apposition of DA and GnRH terminals in ME might permit DA to influence GnRH release. Action of DA transmission probably is mediated by axo-axonic contacts between GnRH and DA fibers in the ME. Dopamine transmission does not normally regulate pulsatile LH release, but under certain conditions, increased DA transmission inhibit LH pulse. Endogenous opioid acts to suppress the secretion of GnRH into hypophysial portal circulation, thereby inhibiting gonadotropin secretion. However, an interaction between endogenenous opioid peptides and gonadotropin release is a complex one which involves ovarian hormones as well. LH secretion appears to be most suppressed by endogenenous opioids during the luteal phase, at a time of elevated progesterone secretion. The arcuate nucleus contains not only cell bodies for GnRH and ${\beta}-endorphin$ but also a dense aborization of fibers suggesting that GnRH release is changed by the interactions between GnRH and ${\beta}-endorphin$ cell bodies within the arcuate nucleus. The frequency and amplitude of pulsatile LH release seem to be increased during the preovulatory gonadotropin surge. Estradiol exerts positive feedback action on the hypothalamo-pituitary axis to trigger preovulatory LH surge. GnRH is also crucial hormonal stimulus for preovulatory LH surge. It is unlikely, however, that increased secretion of GnRH during the preovulatory gonadotropin surge represents an obligatory neural signal for generation of the LH discharge in primates including human. Modulation of preovulatory LH surge by catecholamines has been studied almost exclusively in rats. NE and E may be involved in distinct way to accumulate GnRH in the MBH and its release into the hypophysial portal system during the critical period for LH surge on proestrus in rats. However, the mechanisms whereby augmented adrenergic transmission may facilitate the formation and accumulation of GnRH in the ME-ARC nerve terminals before the LH surge have not been clearly understood.

• 한국수정란이식학회지
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• 제33권4호
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• pp.297-304
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• 2018

The purpose of the present study was to determine the elaborate characteristics of ovarian changes including follicles and corpus luteum, and hormonal patterns of gonadotropin surge mode secretions during the normal consecutive estrous cycle in three dairy cows. Non-lactating and multiparous Holstein cows (n=3) used as experimental animals. The cows were assigned to examine the relationship among ovarian changes (follicle, corpus luteum), ovarian steroids (estradiol, progesterone) and gonadotropin (LH, FSH) surge mode secretion during the successive estrous cycles by rectal palpation, ultrasonography and hormonal assay. The mean length of the estrous cycle for the three cows was $23.1{\pm}1.44days$ (${\pm}SEM$), with a range of 20-28 days. In six estrous cycles, the number of two follicular waves, three follicular waves and four follicular waves was 2, 3 and 1, respectively. The sequential ultrasonographic monitoring showed that the corpus luteum with ${\geq}10mm$ in diameter detected from Day 2 (Day 0 is ovulation) in six estrous cycles of all cows. Preovulatory increases in estradiol concentration reached $10.36{\pm}1.10pg/ml$ on the 2 days before ovulation of the last dominant follicle. All cows exhibited a preovulatory rise in estradiol concentration followed by a typical preovulatory LH and FSH surge. The mean interval from the peak of LH/FSH surge to ovulation of the last dominant follicle was $31.3{\pm}1.76h$ (${\pm}SEM$). In these results, each dairy cow showed that ovarian morphological changes and gonadotropin surge mode secretion will be regulated by various environmental factors including age, breeds, nutrition, breeding conditions, etc.

• Clinical and Experimental Reproductive Medicine
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• 제20권1호
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• pp.37-43
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• 1993

In 27 patients with the past history of poor response to the gonadotropin superovulation induction due to poor follicular growth or permature surge of endogenous luteinizing hormone, the effectiveness of pituitary supperssion with the gonadotropin releasing hormone agonist(GnRH-a) in in vitro fertilization(IVF) program was evaluated in 43 cycles using a combination regimen of D-Trp-6 LHRH(Decapeptyl, Ferring)and FSH/hMG from June, 1989 to August, 1990 at Korea University Hospital IVF Clinic. At midluteal phase of menstrual cycle, Decapeptyl-CR was administered by long-term protocol to minimize initial agonistic effect of endogenous gonadotropins. After the confirmation of pituitary suppression, about 2-3 weeks after GNRH-a administration, ovarian follicle growth was stimulated with FSH/hMG and followed by transvaginal ultrasonic measurement of follicle size and by monitoring of serm E2 and LH if necessary. When compared with the control group stimulated with gonadotropin regimen only, the cancellation rate and occurrence rate of premature LH surge during gonadotropin treatment were significantly lower in study group(11.6% and 2.4%, respectively). There is no significant differences in the mean number of aspirated oocytes, fertilization/cleavage rate, embryo transfer(ET) rate, and mean number of embryos transferred between the two groups. The pregnancy rate per treatment cycle, 16.3%, and per ET cycle, 23.3%, were significantly higher in the study group compared with those of control group. These data suggest that GnRH-a therapy is effective for previous poor responder In gonadotropin superovulation induction for IVF.

• Clinical and Experimental Reproductive Medicine
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• 제26권3호
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• pp.389-398
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• 1999

Objective: This study was designed to evaluate the effects of endogenous LH surge, GnRH agonist (GnRH-a) or human chorionic gonadotropin (hCG) as ovulation trigger on pregnancy rate by intrauterine insemination (IUI). Method: Patients received daily 100 mg of clomiphene citrate (CC) for 5 days starting on the third day of the menstrual cycle followed by human menopausal gonadotropin (hMG) for ovulation induction. Follicles larger than >16 mm in diameter were present in the ovary, frequent LH tests in urine were introduced to detect an endogenous LH surge. Final follicular maturation and ovulation were induced by GnRH-a 0.1 mg (s.c.) or hCG $5,000{\sim}10,000$ IU (i.m.) administration except natural ovulation. Pregnancy was classified as clinical if a gestational sac or fetal cardiac activity was seen on ultrasound. Results: There were no differences in age, duration of infertility and follicle size, but more ampules of hMG were used in GnRH-a group compared to hCG 10,000 IU treated group (p<0.05). Lower level of estradiol ($E_2$) on the day of hCG or GnRH-a injection was observed in hCG 10,000 IU group than other treatment groups (p<0.01). The overall clinical pregnancy rate was 19.8% per cycle (32/162) and 22.2% per patient (32/144). Pregnancy rate was higher in natural-endogenous LH surge group (37.5%, 9/24) than GnRH-a (18.8%) or hCG treated group (20.9% & 13.9%), but this difference was not statistically significant. No patient developed ovarian hyperstimulation. Abortion rate was 22.2% (2/9) in hCG 5,000 IU group. Delivery or ongoing pregnancy rate was 37.5% (9/24), 18.8% (3/16), 16.3% (7/43) and 13.9% (11/79) in endogenous LH surge, GnRH-a, hCG 5,000 IU and hCG 10,000 IU treatment groups, respectively. Conclusion: These results support the concept that use of natural-endogenous LH surge in stimulated cycles may be more effective to obtain pregnancies by IUI than GnRH-a or hCG administration.

• Clinical and Experimental Reproductive Medicine
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• 제7권1_2호
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• pp.3-10
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• 1980

뇌하수체의 성선자극 홀몬 분비 세포는 혈액내 estradiol양의 변화에 따라 LH와 FSH를 분비하므로써 주기적인 변화를 보인다. 성선 자극 홀몬의 분비는 성선 자극 홀몬을 합성하고 보유하는 두가지 형태의 능력의 크기에 의하여 조절되며 이들을 조절하는 것은 시상하부에서 분비되는 황체형성 홀몬-분비 홀몬(LH-RH)과 난소에서 분비되는 estradiol이다. LH-RH는 성선 자극 홀몬 분비세포에 작용하여 성선 자극 홀몬 합성, 저장 및 분비를 촉진시키며 estradiol은 LH-RH의 기능을 확대하고 LH-RH가 self-priming효과를 나타내도록 유도하기도 하며 LH-RH의 성선 자극 홀몬 분비 기능을 저해하기도 한다. Estradiol은 기저성 성선 자극 홀몬을 분비시키기 위하여 negative feedback작용을 하고 배란성 성선 자극 홀몬을 분비시키기 위하여는 positive feedback작용을 하며 feedback작용 부위는 시상하부 및 뇌하수체 전엽이다. 또한, estradiol이 feedback작용을 하여 성선 자극 홀몬의 분비를 조절하는 데는 LH-RH뿐만 아니라 중추신경-시상하부에서 분비되는 dopamine, norepinephrine, prostaglandin등이 참여한다.

• Reproductive and Developmental Biology
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• 제35권3호
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• pp.355-361
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• 2011

Ski protein is implicated in proliferation/differentiation in a variety of cells. We had previously reported that Ski protein is present in granulosa cells of atretic follicles, but not in preovulatory follicles, suggesting that Ski has a role in apoptosis of granulosa cells. The alternative fate of granulosa cells other than apoptosis is to differentiate to luteal cells, however, it is unknown whether Ski is expressed and has a role in granulosa cells undergoing luteinization. Thus, the aim of the present study was to locate Ski protein in the rat ovary during luteinization to predict the possible role of Ski. In order to examine the expression pattern of Ski protein along with the progress of luteinization, follicular growth was induced by administration of equine chorionic gonadotropin to immature female rat, and luteinization was induced by human chorionic gonadotropin treatment to mimic luteinizing hormone (LH) surge. While no Ski-positive granulosa cells were present in preovulatory follicle, Ski protein expression was induced in response to LH surge, and was maintained after the formation of corpus luteum (CL). Though Ski protein is absent in granulosa cells of preovulatory follicle, its mRNA (c-ski) was expressed and the level was unchanged even after LH surge. Taken together, these results demonstrated that Ski protein expression is induced in granulosa cells upon luteinization, and suggested that its expression is regulated post-transcriptionally.

• 한국동물번식학회:학술대회논문집
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• 한국동물번식학회 2002년도 춘계학술발표대회 발표논문초록집
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• pp.72-72
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• 2002

Oocytes maturation, characterized by germinal vesicle (GV) breakdown, formation of the first meiotic spindle, expulsion of the first polar body and arrest in metaphase of second meiotic division (MII), occurs in preovulatory follicles in response to the surge of gonadotropin and leads to an ovulated oocyte in vivo. However, meiotic resumption in vitro occurs spontaneously following removal of cumulus-oocytes complexes (COCs) from the follicle. (omitted)

• 한국수정란이식학회지
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• 제7권2호
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• pp.117-124
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• 1992

미성숙 래트의 외경정맥에 카테타를 장착하고, 다음날 (28일령) 대조군에는 4IU, 다배란 처치 군에는 20IU의 PMSG를 피하주사하였다. 각 실험동물은 혈중의 LH농도 변화를 측정하기 위하여 PMSG 투여 직전 (0시간), 투여후 12시간, 그 이후 6시간 간격으로 혈액을 채취하고 72시간에 희생시켰다. 그 결과 다배란 용량의 PMSG 투여는 먼저 배란반응 및 난소중량을 대조군에 비하여 각각 4,7배 및 2.1배나 현저하게 (P<0.05) 증가시켰다. 그리고 혈청 LH농도는 Radioimmunoassay(RIA)에 의하여 결정되었는데, 먼저 두 군 모두 두 개의 분명한 peak을 가진 경시적 변화관계를 보였다. 즉 이들 두 군네 있어서 LH농도 변화는 0-18시간대에 처음으로 완만한 증가와 54-60시간대에 두번째는 급격한 증가(surge)를 보였다. 그러나 두 군간에 LH농도의 크기는 현저하게 달라, 다배란처치군의 동물에 있어서는 두번째의 LH peak에 앞서 전반적인 LH농도가 대조군보다 현저하게 (P<0.001) 높았으며, 반대로 PMSG 투여후 60시간에 일어나는 peak에 있어서는 LH농도가 대조군보다 현저하게 (P<0.001) 54%나 낮았다. 덧붙여 두 peak간의 증가폭은 대조근에 비하여 다배란 처치군에서 훨씬 낮았다. 본 열구 결과는 PMSG 처치된 래트에 있어서 두 가지의 분명한LH peak의 존재를 정의하며, 다배란 처치에 따른 난소과잉 자극과 내인성 LH surge의 감소와의 연관성을 밝힌다.

• 대한수의학회지
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• 제34권4호
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• pp.735-744
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• 1994

미성숙 래트의 외경정맥에 카테타를 장착하고, 다음날(28일령) 대조군에는 4IU, 다배란처치군에는 20IU의 PMSG를 피하 주사하였다. 각 실험동물은 혈중의 LH농도 변화를 측정하기 위하여 PMSG 투여직전(0시간), 투여후 12시간, 그 이후 6시간 간격으로 혈액을 채취하고 72시간에 희생시켰다. 그 결과 다배란용량의 PMSG 투여는 먼저 배란반응을 대조군에 비하여 4.0배나 현저하게(P<0.05) 증가시켰다. 또한 난관으로부터 회수된 다배란난자는 상당히 다른 감수분열상의 핵성숙도를 나타내었는데, 즉 prophase I이 14.7%, anaphase I이 36.2%, telophase I이 10.3%, metaphase I/II가 32.4%이었다. 그러나 대조군의 래트에서는 대다수(94.0%)의 난자가 한결같이 metaphase II상을 보였다. 그리고 혈청 LH농도는 radioimmunoassay(RIA)에 의하여 결정되었는데, 먼저 두군 모두 두개의 분명한 peak을 가진 경시적 변화관계를 보였다. 즉 이들 두군에 있어서 LH농도변화는 0-18시간대에 처음으로 완만한 증가와 54-60시간대에 두번째의 급격한 증가(surge)를 보였다. 그러나 두군간에 LH농도의 크기는 현저하게 달라, 다배란처치군의 동물에 있어서는 두번째의 LH peak에 앞서 전반적인 LH농도가 대조군보다 현저하게(P<0.001) 높았으나, FMSG 투여후 60시간에 일어나는 peak에 있어서는 LH농도가 대조군보다 현저하게(P<0.001) 54%나 낮았다. 덧붙여 두 peak간의 증가폭은 대조군에 비하여 다배란처치군에서 훨씬 낮았다. 다배란래트에 있어서 54시간 이전에 최초로 연속적인 증가를 보인 고농도의 혈청 LH는 실제적으로 투여된 PMSG와 측정시의 LH항체와의 교차반응(cross-reaction)에 의한 결과로 판명되었고, 한편 54시간과 60시간에 있어서 두번째로 급격한 증가를 보인 혈청 LH는 주로 뇌하수체로부터 분비되는 내재성 LH surge에 의한 것으로 사료된다. 본 연구 결과는 PMSG투여된 래트에 있어서 혈청 LH의 경시적인 변화상 및 그 특징을 정의한다. 그리고 전체적인 연구결과는 첫째, 다배란용량의 PMSG투여에 따른 배란반응의 증가가 주로 PMSG 자체에 함유된 고나도트로핀 작용과 연관이 있고, 둘째, 미성숙 또는 부동기적 핵성숙을 보이는 다배란난자의 회수는 최초의 혈청 LH의 연속적인 증가 및 이의 연이은 감퇴로 특징지워지는 LH활동도의 비정상적 혈중변화에 기인함을 시사한다.

• Clinical and Experimental Reproductive Medicine
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• 제17권1호
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• pp.29-44
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• 1990

In 105 patients with the past history of poor response to the previous controlled ovarian hyperstimulation(COH) due to poor follicular growth or premature LH surge, the effectiveness of pituitary suppression with gonadotropin-releasing hormone agonist(GnRH agonist) in IVF/GIFT program was evaluated in 112 cycles of COH using a combination regimen of Leuprolide acetate (Lupron TAP Pharmaceuticals, USA) and FSH/hMG or pure FSH from May to December, 1989 at SNUH. Starting on day 21 of the menstrual cycle(MCD #21, Day 1), Lupron (1.0mg/day, subcutaneous) was administered once a day till next MCD #3(suppression phase). After the confirmation of pituitary suppression, ovarian follicular growth was stimulated with FSH/hMG or pure FSH from MCD #3(Day + 1), and Lupron was continued with hMG or FSH until hCG administration (D 0) (stimulation phase). After suppression phase, serum E2 level decreased from 183.7${\pm}$95.1(Day 1) to 17.4${\pm}$12.3pg/ml (Day +1), and serum progesterone level from 19.17${\pm}$8.67 to 0.12${\pm}$0.05ng/ml. But there was no decresas in serum LH and FSH levels; LH from 12.74${\pm}$6.21 to 15.49${\pm}$4.93mIU/ml,FSH from 7.60${\pm}$3.84 to 8.58${\pm}$3.15 rnlU/ml. There was no occurrence of premature LH surge during COH. Eleven cycles(9.8%) were cancelled due to poor follicular growth during stimulation phase, and 3 cycles (3.0%) failed in the transvaginal oocytes fretrieval. Serum E2 level was 1366.8${\pm}$642.4 on D 0 and 1492.3${\pm}$906.9pg/ml on D+1. 7.00${\pm}$3.32 follicles(FD${\geq}$12mm) were observed on D 0, and 6.11${\pm}$4.15 oocytes were retrieved, with the oocyte retrieval rate per follicle of 95.0%. 3.59${\pm}$2.57 oocytes were fertilized and cleaved with the oocyte cleavage rate of 55.7%. In 83 IVF patients, 4.08${\pm}$2.39 embryos were transferred, and 16 pregnancies were obtained with the pregnancy rate per ET 2.39 mebryos were transferred, and 16 pregnancies were obtained with the pregnancy rate per ET of 19.3%. In 6 GIFT patients, 7.83${\pm}$3.31 oocytes were retrieved and transferred with maximum number of 6, but no pregnancy was obtained. When compared with the previous 108 cycles of COH using FSH/hMG or pure FSH regimen, the cancellation rate during COH was significantly decreased, and all the parameters of the outcome of COH including the pregnancy rate were increased. These data suggest that GnRH agonist therapy for pituitary suppression is an effective adjunct to the current gonadotropin regimens for COH in IVF/GIFT and can increase the probability of oocytes retrieval and pregnancy, especially in the previous poor responders.