• Biomolecules & Therapeutics
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• v.9 no.3
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• pp.209-217
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• 2001

This study was attempted to investigate on renal effect of ($\pm$)6-chloro-7,8-dihydroxy-1-phenol 2,3,4,5-tetrahydro-lH-3 benzazepine (SKF 81297), dopamine $D_1$ receptor agonist, in dog. SKF 81297, when gluten intravenously, produced diuretic action along with the increases of renal plasma flow (RPF), glomerular filtration rate (GFR), amounts of N $a^{+}$ and $K^{+}$ excreted into urine ( $E_{Na}$ , $E_{K}$) and osmolar clearance ( $C_{osm}$). It also decreased the reabsorption rates of N $a^{+}$ and $K^{+}$ in renal tubule ( $R_{Na}$ , $R_{K}$) and free water clearance ( $C_{H2O}$), whereas ratios of $K^{+}$ agonist N $a^{+}$ in urine and filtration fraction (FF) was not changed. SKF 81297, when administered into a renal artery, elicited diuresis both in experimental kidney given the SKF 81297 and control kidney not given, while the effect was more remarkable in experimental kidney than those exhibited in control kidney. SKF 81297 given into carotid artery also exhibited diuresis, the potency at this time, compared to those induced by intravenous SKF 81297, was magnusgreat. Above results suggest that SKF 81297 produces diuresis by both indirect action through changes of central function and direct action being induced in kidney. Central diuretic action is mediated by improvement of renal hemodynamics, but direct action by inhibition of electrolytes reabsorption in renal tubule.enal tubule. tubule.

• Clinical and Experimental Reproductive Medicine
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• v.43 no.3
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• pp.169-173
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• 2016

Objective: To determine the preferred regimen for women with adenomyosis undergoing in vitro fertilization (IVF), we compared the IVF outcomes of fresh embryo transfer (ET) cycles with or without gonadotropin-releasing hormone (GnRH) agonist pretreatment and of frozenthawed embryo transfer (FET) cycles following GnRH agonist treatment. Methods: This retrospective study included 241 IVF cycles of women with adenomyosis from January 2006 to January 2012. Fresh ET cycles without (147 cycles, group A) or with (105 cycles, group B) GnRH agonist pretreatment, and FET cycles following GnRH agonist treatment (43 cycles, group C) were compared. Adenomyosis was identified by using transvaginal ultrasound at the initial workup and classified into focal and diffuse types. The IVF outcomes were also subanalyzed according to the adenomyotic region. Results: GnRH agonist pretreatment increased the stimulation duration ($11.5{\pm}2.1days$ vs. $9.9{\pm}2.0days$) and total dose of gonadotropin ($3,421{\pm}1,141IU$ vs. $2,588{\pm}1,192IU$), which resulted in a significantly higher number of retrieved oocytes ($10.0{\pm}8.2$ vs. $7.9{\pm}6.8$, p=0.013) in group B than in group A. Controlled ovarian stimulation for freezing resulted in a significantly higher number of retrieved oocytes ($14.3{\pm}9.2$ vs. $10.0{\pm}8.2$, p=0.022) with a lower dose of gonadotropin ($2,974{\pm}1,112IU$ vs. $3,421{\pm}1,141IU$, p=0.037) in group C than in group B. The clinical pregnancy rate in group C (39.5%) tended to be higher than those in groups B (30.5%) and A (25.2%) but without a significant difference. Conclusion: FET following GnRH agonist pretreatment tended to increase the pregnancy rate in patients with adenomyosis. Further largescale prospective studies are required to confirm this result.

• Biomolecules & Therapeutics
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• v.29 no.5
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• pp.519-526
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• 2021

In a search for effective PPAR-γ agonists, 110 clinical drugs were screened via molecular docking, and 9 drugs, including parecoxib, were selected for subsequent biological evaluation. Molecular docking of parecoxib to the ligand-binding domain of PPAR-γ showed high binding affinity and relevant binding conformation compared with the PPAR-γ ligand/antidiabetic drug rosiglitazone. Per the docking result, parecoxib showed the best PPAR-γ transactivation in Ac2F rat liver cells. Further docking simulation and a luciferase assay suggested parecoxib would be a selective (and partial) PPAR-γ agonist. PPAR-γ activation by parecoxib induced adipocyte differentiation in 3T3-L1 murine preadipocytes. Parecoxib promoted adipogenesis in a dose-dependent manner and enhanced the expression of adipogenesis transcription factors PPAR-γ, C/EBPα, and C/EBPβ. These data indicated that parecoxib might be utilized as a partial PPAR-γ agonist for drug repositioning study.

• Animal cells and systems
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• v.13 no.2
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• pp.205-212
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• 2009

Known as a female hormone, estrogen, performs important functions, and the activities of the hormone are mediated via the estrogen receptor. The principal objective of the present study was to assess the effects of a estrogen receptor agonist in male reproductive organs. In this study, the estrogen receptor alpha agonist, PPT, was injected subcutaneously into adult male mice. The effects of PPT on the murine reproductive system were histologically assessed at 3,5, and 8 weeks after treatment. In the treatment group, reductions were observed in the weight of the body, testis and epididymis. Microscopic examination revealed a reduction in seminiferous tubular diameter in the testis, and epithelial cell height in the epididymis during the experiment. 8 weeks after treatment, spermatogenesis was not detected, nor was the lumen of the seminiferous tubules. In the fertility test, 1 week after PPT injection, the fertilizing ability of males was decreased, and on the 2nd and 3rd weeks, complete infertility was observed. In conclusion, the injection of high concentrations of PPT into adult males induced physiological changes, including infertility, and also induced morphological changes, including a reduction in the height of epithelial cells within the reproductive system.

• Clinical and Experimental Reproductive Medicine
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• v.45 no.3
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• pp.135-142
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• 2018

Objective: To prospectively evaluate the efficacy and safety of a fixed early gonadotropin-releasing hormone (GnRH) antagonist protocol compared to a conventional midfollicular GnRH antagonist protocol and a long GnRH agonist protocol for in vitro fertilization (IVF) in patients with polycystic ovary syndrome (PCOS). Methods: Randomized patients in all three groups (early antagonist, n = 14; conventional antagonist, n = 11; long agonist, n = 11) received 21 days of oral contraceptive pill treatment prior to stimulation. The GnRH antagonist was initiated on the 1st day of stimulation in the early antagonist group and on the 6th day in the conventional antagonist group. The GnRH agonist was initiated on the 18th day of the preceding cycle. The primary endpoint was the number of oocytes retrieved, and the secondary endpoints included the rate of moderate-to-severe ovarian hyperstimulation syndrome (OHSS) and the clinical pregnancy rate. Results: The median total number of oocytes was similar among the three groups (early, 16; conventional, 12; agonist, 19; p= 0.111). The early GnRH antagonist protocol showed statistically non-significant associations with a higher clinical pregnancy rate (early, 50.0%; conventional, 11.1%; agonist, 22.2%; p= 0.180) and lower incidence of moderate-to-severe OHSS (early, 7.7%; conventional, 18.2%; agonist, 27.3%; p= 0.463), especially among subjects at high risk for OHSS (early, 12.5%; conventional, 40.0%; agonist, 50.0%; p= 0.324). Conclusion: In PCOS patients undergoing IVF, early administration of a GnRH antagonist may possibly lead to benefits due to a reduced incidence of moderate-to-severe OHSS in high-risk subjects with a better clinical pregnancy rate per embryo transfer. Further studies with more subjects are required.

• 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.

• Clinical and Experimental Reproductive Medicine
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• v.37 no.3
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• pp.239-244
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• 2010

Objective: The objective of this retrospective study was to compare the in vitro fertilization (IVF) outcomes of gonadotropinreleasing hormone (GnRH) agonist and GnRH antagonist protocols in poor responders. Methods: A total of 172 cycles in subjects with less than 5 oocytes retrieved treated with either GnRH agonist long protocols or antagonist protocols were included. The outcome variables such as numbers of growing follicles and retrieved oocytes, and the fertilization rate were evaluated as the main outcome measures. Results: There was no difference in regard to the numbers of growing follicles and oocytes, and fertilization rate between the two groups. $E_2$ level on Day 7/8, mean gonadotropin dose, and the days of stimulation were shown to be statistically different (p<0.01, respectively). Conclusion: Considering that similar results were observed with less time and gonadotropin dose, GnRH antagonist protocol may be considered as a preferable choice over GnRH agonist protocols in poor responders.

• Journal of Breast Disease
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• v.6 no.2
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• pp.46-51
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• 2018

Purpose: Endocrine therapy is the preferred treatment for hormone receptor (HR)-positive metastatic breast cancer (MBC). We investigated the efficacy of combined aromatase inhibitor (AI) and luteinizing hormone-releasing hormone (LHRH) agonist in premenopausal patients with HR-positive MBC. Methods: We retrospectively analyzed the medical records of 21 HR-positive premenopausal MBC patients treated with combined AI and LHRH agonist therapy. Results: The median follow-up period was 32.9 months. The overall response rate was 47.6%, with three complete responses (14.3%) and seven partial responses (33.3%). Nine patients (42.9%) achieved stable disease lasting more than 6 months; thus, the clinical benefit rate was 90.4%. The median time to progression was 45.4 months. No patients experienced grade 3 or 4 toxicity. Conclusion: Combined AI and LHRH agonist treatment safely and effectively induced remission or prolonged disease stabilization, suggesting that this could be a promising treatment option for HR-positive premenopausal patients with MBC.

• Biomolecules & Therapeutics
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• v.13 no.3
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• pp.138-142
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• 2005

Adenosine and GABA are known to be major inhitory neurotransmitters in the central nervous system and its receptors mediate various neurophamacological effects including cardiovascular modulatory effects. Inhibitory cardiovascular effects induced by intrathecal (i.t.) administration of adenosine $A_1$ receptor agonist and its modulation by cyclic AMP was suggested by our previous report. In this experiment, we examined the modulation of cardiovascular effects of adenosine $A_1$ receptor and adenosine $A_2$ receptor by $GABA_B$ receptors antagonist in the spinal cord. I.t. administration of 10 nmol of $N^6$-cyclohexyladenosine (CHA, an adenosine $A_1$ receptor agonist), I.t. administration of 2 nmol of 5'-(N-cyclopropyl)-carboxamidoadenosine (CPCA, an adenosine $A_2$ receptor agonist), pretreatment with 5-aminovaleric acid (a $GABA_B$ receptor antagonist, 50 nmol, i.t.) prior to administration of CHA and pretreatment with 5-aminovaleric acid (a $GABA_B$ receptor antagonist, 50 nmol, i.t.) prior to administration of CPCA were performed in anesthetized, artificially ventilated Sprague-Dawley rats. I.t. administration of 50 nmol of 5-aminovaleric acid significantly attenuated the inhibitory cardiovascular effects of CHA but did not attenuated the inhibitory cardiovascular effects of CPCA. It is suggested that cardiovascular responses of adenosine $A_1$ receptor is modulated by $GABA_B$ receptor and adenosine $A_2$ receptor is not modulated by $GABA_B$ receptor in the spinal cord.

• International Journal of Oral Biology
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• v.31 no.4
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• pp.135-140
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• 2006

Temperature signaling can be initiated by members of transient receptor potential (thermo-TRP) channels. Hot and cold substances applied to teeth usually elicit pain sensation. Since odontoblasts constitute a well-defined layer between the pulp and the mineralized dentin, being first to encounter thermal stimulation from oral cavity, they may be involved in sensory transduction process, in addition to their primary function as formation of dentin. We investigated whether thermo-TRP channels are expressed in a odontoblast cell line, MDPC-23. The expressions of thermo-TRP channels were examined using reverse transcription polymerase chain reaction (RT-PCR), immunohistochemistry, fluorometric calcium imaging. Analysis of RT-PCR revealed mRNA expression of TRPV1, TRPV2, TRPV4 and TRPM8, but no TRPV3, TRPA1. Immunohistochemical approach failed to detect TRPV1 expression. Whereas the application of 4-phorbol-12,13-didecanoate($10\;{\mu}M$, a TRPV4 agonist), menthol(1 mM, a TRPM8 agonist) and icilin($10\;{\mu}M$, a TRPM8 agonist) produced the enhancement of intracellular calcium concentration, capsaicin($1\;{\mu}M$, a TRPV1 agonist) did not. Our results suggest that subfamily of thermo-TRP channels expressed in odontoblasts may serve as thermal or mechanical transducer in teeth.