• Clinical and Experimental Pediatrics
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• v.53 no.9
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• pp.845-851
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• 2010

Purpose: Recombinant human growth hormone (rhGH) has been widely used to treat short stature. However, there are some concerns that growth hormone treatment may induce skeletal maturation and early onset of puberty. In this study, we investigated whether rhGH can directly affect the neuronal activities of of gonadotropin-releasing hormone (GnRH). Methods: We performed brain slice gramicidin-perforated current clamp recording to examine the direct membrane effects of rhGH on GnRH neurons, and a whole-cell voltage-clamp recording to examine the effects of rhGH on spontaneous postsynaptic events and holding currents in immature (postnatal days 13-21) and adult (postnatal days 42-73) mice. Results: In immature mice, all 5 GnRH neurons recorded in gramicidin-perforated current clamp mode showed no membrane potential changes on application of rhGH (0.4, $1{\mu}g/mL$). In adult GnRH neurons, 7 (78%) of 9 neurons tested showed no response to rhGH ($0.2-1{\mu}g/mL$) and 2 neurons showed slight depolarization. In 9 (90%) of 10 immature neurons tested, rhGH did not induce any membrane holding current changes or spontaneous postsynaptic currents (sPSCs). There was no change in sPSCs and holding current in 4 of 5 adult GnRH neurons. Conclusion: These findings demonstrate that rhGH does not directly affect the GnRH neuronal activities in our experimental model.

• Journal of Embryo Transfer
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• v.24 no.3
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• pp.169-176
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• 2009

Domestic bitches are non-seasonally monoestrus; spontaneously ovulate only once or twice occurs at anytime of the year. Estrus induction has been applied infrequent estrus, misleading ovulation, mating difficulties, failure to conceive after normal mating, pregnancy failure and biological research. Protocol of estrus induction which included variable hormones such as FSH, GnRH, and PMSG have been applied for the last decades. Recently, Bromocriptine, one of anti-prolatin/dopamine agonist has been occasionally applied for estrus induction. The study was carried out to investigate the effective method for the induction of estrus in bitches using different hormone treatments, and the initiation time of estrus from hormone treatment by assessments of cytological observation and blood plasma progesterone concentration. A total of 54 bitches on anestrus were selected for the study and divided randomly into 8 treatment groups as follow. Control, natural estrus; FSH (L), FSH (1.5 mg/kg, twice a day, $Falltrophin^{(R)}$, Vetrepharm); FSH (H), FSH (3.0 mg/kg, twice a day); GnRH+FSH, GnRH (5 ug/kg, once first day, $GNADON^{(R)}$, Dongbang)+FSH (3 mg/kg, SID); PMSG, PMSG (50 IU/kg, every third day $FOLLIGON^{(R)}$, Intevet); GnRH+PMSG, GnRH (5 ug/kg, only first day)+PMSG (50 IU/kg, every third day); GnRH, GnRH (5 ug/kg, only first day); Bromocriptine, bromocriptine (0.3 mg/kg, SID, $Parlodel^{(R)}$, Novartis). The bitches were evaluated clinical sign, cytological exam and $OVUCHECK^{(R)}$ Premate for assessment of estrus induction. Estrus induction rates were significantly (P<0.05) higher in GnRH+PMSG (100%) compared to others. PMSG and GnRH+PMGS (87.5 and 100%) and Bromocriptine (77.8%) were higher than others except GnRH+PMSG. Analysis of vaginal smear has proved to be effective a correct assessment of estrus induction with assay of progesterone concentration by $OVUCHECK^{(R)}$ Premate. Proestrus initiated by the $6^{th}$ after induction in most case. In conclusion, bromocriptine is an effective drug for estrus induction in bitches and assay of progesterone concentration by $OVUCHECK^{(R)}$ Premate with examination of vaginal smear that should be useful to detection of estrus induction of estrus induced bitches.

• Clinical and Experimental Reproductive Medicine
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• v.19 no.2
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• pp.175-179
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• 1992

The factors involved in the initial neoplastic transformation and subsquent growth of uterine fibroid are poorly understood. The reduction in uterine fibroid volume associated with the chronic administration of the mechanisms mediating the decrease in fibroid volume in GnRH-a treated patients are poorly defined. The purpose of this study was to determine the proliferating cell nuclear antigen(PCNA) in fibroid from-women pretreated with GnRH analogue(GnRH-a) compared with controls. Tissue was obtained from 16 premenopausal women with uterine fibroid who received GnRH-a(D-Trp6-GnRH) intramusculary every 28 days for four injections. The mean proliferating index(PI) in patients with uterine fibroids was $2.25{\pm}0.9$, and in controls was $8.82{\pm}1.8$(P<0.001). The proliferating index was not corrleated with the reduction of fibroid volume. In this clinical study, although hypoestrogenism may be the main factor that reduce the volume of fibroid, other factors are also considered to be involved in that process. And the regrowth of uterine fibroid may be affected by increased production of PCNA after stopping GnRH-a.

• Journal of Veterinary Clinics
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• v.22 no.4
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• pp.428-430
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• 2005

A female French Bulldog was referred to Veterinary Medical Teaching Hospital, Chungbuk National University. In case, alopecia and erythema nodosum were the main complaints in a 16 months old female dog. Ventral alopecia and dorsal erythema nodosum have been presented on skin lesions for 8 months. There were no specific change with CBC and blood chemistry but plasma estrogen concentration was 68 pg/ml and cornified superficial epithelial cells were detected above $90\%$ by cytology examination of vaginal smear preparation. Ovarian cyst was detected by ultrasonography in the left ovary. Cystic diameter was $14.2\times12.0mm$. Therefore, we diagnosed as unilateral multiple follicular cysts. The dog was treated with GnRH $50{\mu}g$ injection by intramuscularly Cyst size was decreased $7.3\times7.2mm$ after 7 days GnRH treatment and disappeared after 14 days GnRH treatment. Also dermatitis by unilateral multiple follicular cysts were recovered after 21 days GnRH treatment.

• Clinical and Experimental Reproductive Medicine
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• v.32 no.4
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• pp.315-324
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• 2005

Objectives: To compare the efficacy of GnRH antagonist multiple dose protocol (MDP) with that of GnRH agonist long protocol (LP) in controlled ovarian hyperstimulation for in vitro fertilization in patients with high basal FSH (follicle stimulating hormone) level or old age, a retrospective analysis was done. Methods: Two hundred ninety four infertile women (328 cycles) who were older than 41 years of age or had elevated basal FSH level (> 8.5 mIU/mL) were enrolled in this study. The patients had undergone IVF-ET after controlled ovarian hyperstimulation using GnRH antagonist multiple dose protocol (n=108, 118 cycles) or GnRH agonist long protocol (n=186, 210 cycles). The main outcome measurements were cycle cancellation rate, consumption of gonadotropins, the number of follicles recruited and total oocytes retrieved. The number of fertilized oocytes and transferred embryos, the clinical pregnancy rates, and the implantation rates were also reviewed. And enrolled patients were divided into three groups according to their age and basal FSH levels; Group A - those who were older than 41 years of age, Group B - those with elevated basal FSH level (> 8.5 mIU/mL) and Group C - those who were older than 41 years of age and with elevated basal FSH level (> 8.5 mIU/mL). Poor responders were classified as patients who had less than 4 retrieved oocytes, or those with $E_2$ level <500 pg/mL on the day of hCG injection or those who required more than 45 ampules of exogenous gonadotropin for stimulation. Results: The cancellation rate was lower in the GnRH antagonist group than in GnRH agonist group, but not statistically significant (6.8% vs. 9.5%, p=NS). The amount of used gonadotropins was significantly lower in GnRH antagonist group than in agonist group ($34.8{\pm}11.3$ ampules vs. $44.1{\pm}13.4$ ampules, p<0.001). The number of follicles > 14 mm in diameter was significantly higher in agonist group than in antagonist group ($6.7{\pm}4.6$ vs. $5.0{\pm}3.4$, p<0.01). But, there were no significant differences in clinical pregnancy rate (24.5% in antagonist group vs. 27.4% in agonist group, p=NS) and implantation rate (11.4% in antagonist group vs. 12.0% in agonist group, p=NS) between two groups. Mean number of retrieved oocytes was significantly higher in GnRH agonist LP group than in GnRH antagonist MDP group ($5.4{\pm}3.5$ vs. $6.6{\pm}5.0$, p<0.0001). But, the number of mature and fertilized oocytes, and the number of good quality (grade I and II) and transferred embryos were not different between two groups. In each group A, B, and C, the rate of poor response did not differ according to stimulation protocols. Conclusions: In conclusion, for infertile women expected poor ovarian response such as who are old age or has elevated basal FSH level, a protocol including a controlled ovarian hyperstimulation using GnRH antagonist appears at least as effective as that using a GnRH agonist, and may offer the advantage of reducing gonadotropin consumption and treatment period. However, much work remains to be done in optimizing the GnRH antagonist protocols and individualizing these to different cycle characteristics.

• Journal of Veterinary Clinics
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• v.26 no.6
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• pp.647-649
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• 2009

An orchiopexy was performed in an 18-month old adult English bulldog with bilateral cryptorchidism. One month postoperatively, the dog was twice-treated with GnRH (50 ug/kg) at an interval of 2 weeks. Semen was collected and evaluated before and after surgery. Fertility was determined by artificial insemination. No spermatozoa were observed before orchiopexy and 2 months postoperatively. However, 6 live sperm were detected 4 months postoperatively and normal sperm characteristics (except sperm concentration) were present 7 months postoperatively. A female bulldog, inseminated with the semen from the bulldog 8 months postoperatively, delivered 6 offsprings. Spermatogenesis and spermatozoa with fertilizing capacity were recovered by postpubertal orchiopexy and GnRH therapy in a bilateral cryptorchid dog.

• Clinical and Experimental Reproductive Medicine
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• v.44 no.2
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• pp.57-62
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• 2017

The purpose of this paper is to assimilate all data pertaining to the use of gonadotropin-releasing hormone (GnRH) antagonists in in vitro fertilization cycles after ovulation trigger to reduce the symptoms of ovarian hyperstimulation syndrome (OHSS). A systematic review of the literature was performed to identify all studies performed on the use of a GnRH antagonist in IVF cycle post-ovulation trigger with patients at high risk for OHSS. Ten studies were identified and reviewed. Descriptions of the studies and their individual results are presented in the following manuscript. Due to significant heterogeneity among the studies, it was not possible to perform a group analysis. The use of GnRH antagonists post-ovulation trigger for treatment of OHSS has been considered for almost 20 years, though research into its use is sparse. Definitive conclusions and recommendations cannot be made at this time, though preliminary data from these trials demonstrate the potential for GnRH antagonists to play a role in the treatment of OHSS in certain patient populations.

• Clinical and Experimental Reproductive Medicine
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• v.40 no.2
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• pp.60-66
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• 2013

Objective: Impairment of spermatogenesis has been identified as an inevitable side effect of cancer treatment. Although estrogen treatment stimulates spermatogenic recovery from the impaired spermatogenesis by suppressing the intra-testicular testosterone (ITT) level, side effects of estrogen are still major impediments to its clinical application in humans. Soybeans are rich in genistein, which is a phytoestrogen that binds to estrogen receptors and has an estrogenic effect. We investigated the effects of genistein administration on ITT levels, testis weight, and recovery of spermatogenesis in rats treated with a chemotherapeutic agent, busulfan. Methods: Busulfan was administered intraperitoneally to rats, and then a GnRH agonist was injected subcutaneously into the back, or genistein was administered orally. Results: The weight of the testes was significantly reduced by the treatment with busulfan. The testis weight was partially restored after busulfan treatment by additional treatment with either the GnRH agonist or genistein. Busulfan also induced atrophy of a high percentage of the seminiferous tubules, but this percentage was decreased by additional treatment with either the GnRH agonist or genistein. Treatment with genistein was effective at suppressing and maintaining ITT levels comparable to that in the GnRH agonist group. Conclusion: Genistein effectively suppressed ITT levels and stimulated the recovery of spermatogenesis in rats treated with a chemotherapeutic drug. This suggests that genistein may be a substitute for estrogens, for helping humans to recover fertility after cancer therapy without the risk of side effects.

• Journal of Embryo Transfer
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• v.18 no.2
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• pp.115-124
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• 2003

The objective of this study was to compare the effect of four different estrus induction methods in anestrus cows on the estrus induction and pregnancy following artificial insemination (AI). Sixty-five cows (3∼4 years old) were selected and divided into four different estrus induction treatment groups. Group 1, 12 cows were treated by Ovsynch program combined with GnRH and PGF$_2$a. Group 2, 12 cows were treated by "Tow plus Two" program with GnRH and PGF$_2$a. Group 3, 20 cows were treated by "Tow plus Two" program following intravaginal progesterone implantation (CIDR). Twenty one cows in Group 4 were treated by "Tow plus Two" program following follicular rupture and intravaginal progesterone implantation. Cows were then observed estrus induction and inseminated artificially at 12 h and 24 h after standing estrus. The rates of estrus induction in Group 4 (18/21, 86%) was significantly (P<0.05) higher than those in groups 1, 2 and 3 (8/12, 67%; 9/12, 75%; 14/20, 70%). In the mean time of onset of estrus after final administration of GnRH in different hormone-treated cows, the cows in Group 3 (24.2$\pm$2.2) and Group 4 (23.4$\pm$2.0) were significantly (P<0.05) shorter than that in Group 1 (28.5$\pm$4.6) and Group 2 (26.4$\pm$3.3). The rates of pregnancy diagnosed on Day 28 were significantly different between treatment groups. Significantly (P<0.05) higher rate of pregnancy was observed in Group 4 (17/20, 85.0%) than those in Groups 1, 2 and 3 (7/11, 63.6%; 8/12, 66.7%; 15/20, 75.0%, respectetively). The rate of abortion diagnosed on 49 days of gestation was significantly (P<0/05) lower in Group 4 (1/17, 5.9%) than those in Groups 1, 2 and 3 (2/7, 28.7%; 2/8, 25% and 3/15, 20%, respectively). In conclusion, combined treatments with GnRH and PGF$_2$a following follicular rupture and progesterone implant in anestrus cows was considered to be most effective in estrus induction and maintenance of pregnancy. Further studies are needed to verify the functional mechanisms of residual follicles in anestrus ovaries on retarding the response of hormonal treatments.sponse of hormonal treatments.

• Korean Journal of Veterinary Research
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• v.35 no.3
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• pp.603-613
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• 1995

Plasma progesterone($P_4$) assay has been introduced to apply to the differential diagnosis of reproductive disorders and the monitoring of responses of ovarian dysfunction to $PGF_2{\alpha}$ or GnRH treatment in the 204 postpartum and postinsemination subestrus dairy cows. 1. The incidence rate of reproductive disorders in 204 subestrus cows, diagnosed by palpation per rectum and plasma $P_4$ determination using 'Two sample test'(Day 0+Day 10) were as follows; silent heat or error of estrus detection 110(53.9%), persistent corpus luteum 26(12.7%), follicular cyst 16(7.8%), inactive ovary 12(5.9%), luteal cyst 11(5.4%), granulosa cell tumor of ovary 1(0.5%), fetal mummification 1(0.5%), endometritis 15(7.4%) and pyometra 12(5.9%), respectively. 2. After the $PGF_2{\alpha}$ treatment to the 76 cows with silent heat or error of estrus detection, persistent corpus luteum, or luteal cyst, plasma $P_4$ concentrations at day 3 post treatment using 'Two sample test'(Day 0+Day 3) remained low(<1.0ng/ml) in all 76 cows. Therefore all 76 cows responded positively to $PGF_2{\alpha}$ treatment. Seventeen cows with follicular cyst or inactive ovary were treated with GnRH. All 7 cows with follicular cyst and 4 cows with inactive ovary remained high($${\geq_-}1.0ng/ml$$) a plasma $P_4$ concentrations at day 12 post treatment using 'Two sample test'(Day 0+Day 12), but 6 cows with inactive ovary remained low(<1.0ng/ml) a plasma $P_4$ concentrations. Therefore all 7 cows with follicular cyst and 4 cows with inactive ovary responded positively, but 6 cows with inactive ovary responded negatively to GnRH treatment. 3. The mean days from treatment to first service, number of cows conceived on first service(%), mean number of services per conception, mean days from initial treatment to conception, and mean number of cows conceived by 100 days post treatment(%) were 5.0 and 26.2 days, 45(59.2%) and 6(35.3%) cows, 1.5 and 1.7 services, 13.6 and 22.6 days, and 62(81.6%) and 9(52.9%) cows in group of $PGF_2{\alpha}$ and GnRH treatment, respectively. These results indicated that plasma $P_4$ assay was practical as an aid to diagnosing reproductive disorders and to monitoring responses of ovarian dysfunction to $PGF_2{\alpha}$ and GnRH treatment in subestrus cows.