• Clinical and Experimental Pediatrics
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• v.48 no.6
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• pp.669-674
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• 2005

Nephrogenic diabetes insipidus (NDI) is a disorder in which the secretion of antidiuretic hormone is normal, but the response of the renal collecting tubules to vasopressin is impaired. Compared with acquired NDI (a-NDI), which is secondary to chronic bilateral incomplete urinary tract obstruction with hydronephrosis, congenital NDI (c-NDI) is a very rare heritable disorder that usually follows the X- linked recessive pattern. Clinical symptoms of c-NDI can be non specific, and often the disease ultimately results in failure to thrive, or mental retardation. Recently, the diagnosis can be confirmed by direct sequencing analysis of the peripheral blood specimens. The long-term results of treatment for c-NDI are not satisfactory. Reports on the follow up of c-NDI cases are rare and there is no report on the cases treated with combinations of three drugs. We report herein a case of severe c-NDI in an 8 year-old-boy with a severely dysconfigurated urinary tract system. The patient and his mother showed a frameshift mutation on the AVPR2 gene on chromosome Xq28:.847_851delTGCTG (p.C283fsX90). The patient showed normal growth and development by treatment with combinations of hydrochlorothiazide ($65mg/m^2$), amiloride (0.3 mg/kg/d) and indomethacin ($100mg/m^2$), yet after five years he needed adjuvant cystostomy to relieve him from the residual symptoms of urgency with polyuria.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.44 no.1
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• pp.73-79
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• 2018

The primary cilium protrudes from the cell body like a bio-antenna that has many receptors, channels and signaling molecules to sense and response to external stimuli. The external environment such as ultraviolet irradiation, temperature, humidity, gravity and shear stress always influences skin. Skin responds to external stimuli and differentiates by making melanin, collagen and horny layer. Ciliogenesis participates in developmental processes of skin, such as keratinocyte differentiation and hair formation. And it was reported that skin pigmentation was inhibited when ciliogenesis was induced by sonic hedgehog-smoothened-GLI2 signaling. When skin is exposed to ultraviolet irradiation, alpha-melanocyte stimulating hormones (${\alpha}$-MSH) increase melanin synthesis through activation of the cAMP pathway in melanocytes. We observed that ${\alpha}$-MSH and cAMP production inducers inhibited ciliogenesis of melanocytes. Therefore, we thought that regulation of ciliogenesis is potential candidate target for the development of agents to treat undesirable hyperpigmentation of skin. As a result, we found out that an ethanol extract of Glycyrrhiza glabra (EGG) root and 3,4,5-trimethoxy cinnamate thymol ester (TCTE, Melasolv) significantly inhibit melanin synthesis of normal human melanocyte by inducing primary cilium formation. This study proposed new theory to regulate skin pigmentation and cosmetic components for skin whitening.

• Development and Reproduction
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• v.13 no.4
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• pp.207-215
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• 2009

Numerous factors can affect the activities of hypothalamus-pituitary-gonad (HPG) hormonal axis, resulting in alteration of reproductive capacity or status such as onset of puberty and menopause. Soon after the finding of leptin, a multifunctional hormone secreted from adipocytes, a close relationship between reproduction and body energy balance have been manifested. Ghrelin, another multifunctional hormone from gastrointestinal tract, is an endogenous ligand of growth hormone secretagogue receptor (GHSR), and is thought to be a counterpart of leptin in the regulation of energy homeostasis. As expected, ghrelin can also modulate the reproductive capacity through the modulation of activities of HPG axis. This paper summarizes the current knowledge on the discovery, gene structures, tissue distribution and roles of ghrelin and GHSRs in mammalian reproduction in particular modulation of reproductive hormone secretion in HPG axis. Like POMC gene expression in pituitary gland, preproghrelin gene can generate a complex repertoire of transcripts which further undergo alternative splicing and posttranslational modifications. Concerning the roles of preproghrelin gene products in the control of body physiology except energy homeostasis, limited knowledge is available so far. Several lines of evidence, however, show the interplay of ghrelin between metabolism and reproduction. In rat and human, the distribution of ghrelin receptor GHSRs (GHSR1a and GHSR1b) has been confirmed not only in the hypothalamus and pituitary which were originally postulated as target of ghrelin but also in the testis and ovary. Expression of the preproghrelin gene in the brain and gonads was also verified, suggesting the local role (s) of ghrelin in HPG axis. Ghrelin might play a negative modulator in the secretions of hypothalamic GnRH, pituitary gonadotropins and gonadal steroids though the action on pituitary is still questionable. Recent studies suggest the involvement of ghrelin in regulation of puberty onset and possibly of menopause entry. It is now evident that ghrelin is a crucial hormomal component in 'brain-gut' axis, and is a strong candidate links between metabolism and reproduction. Opposite to that for leptin, ghrelin signaling is likely representing the 'hunger' state of body energy balance and is necessary to avoid the energy investment into reproduction which has not a top priority in maintaining homeostasis. Further researches are needed to gain a deep insight into the more precise action mechanism and role of ghrelin in reproduction, and to guarantee the successful biomedical applications.

• Korean Journal of Clinical Laboratory Science
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• v.50 no.4
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• pp.449-456
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• 2018

Cervical cancer is the fourth most frequently diagnosed cancer in women worldwide. In lower Human Development Index countries, it has the second highest incidence and mortality among cancer in women. Therefore, better diagnosis and treatment systems are needed. Among them, estrogen receptor alpha ($ER-{\alpha}$) mRNA expression has been analyzed with RT-qPCR since several studies reported that $ER-{\alpha}$ is necessary in the maturation of the uterus and is related to cervical cancer. In this study, $ER-{\alpha}$ quantitative analysis was performed on various lesions and normal tissue samples. Based on the receiver operating characteristic (ROC) curve, its sensitivity and specificity were 85% and 75%, respectively, showing higher or similar results to those of conventional HPV tests. In addition, its expression level was analyzed with clinical information. With regression analysis, the R square value between the $ER-{\alpha}$ mRNA expression level and menopause status was 0.5041, indicating a strong correlation. This study was performed as part of a pilot study and suggests that $ER-{\alpha}$ is related to carcinogenesis. Future studies will examine other hormones and menopausal factors with a larger sample size.

• Korean Journal of Animal Reproduction
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• v.26 no.3
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• pp.299-308
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• 2002

In horse, a single gene encodes both eCG and eLH $\beta$ subunits. The difference between eCG and eLH lies in the structure of their glycoresidues, which are both sialylated and sulfated in LH and sialylated in CG eCG consists of highly glycosyiated $\alpha$- and $\beta$-subunits and is an unique member of the gonadotropin family because it elicits response characteristics of both FSH and LH in other species than the horse. This dual activity of eCG in heterologous species is of fundamental interest to the study of gonadotropin structure-function relationships and the understanding of the molecular bases of the specific interactions of these hormones with their receptors. Thus, eCG is a dintinct molecule from the view points of its biological function and glycoresidue structures. The oligosaccharide at Asn 56 of the $\alpha$-subunit plays an indispensable role, whereas the carboxyl-terminal extension of the eCG $\beta$-subunit with its associated O-linked oligosaccharides is not improtant for, the in vitro LH-like activity of eCG. In contrast, both N- and O-linked oligosaccharides play important roles for FSH-like activity and increase FSH-like activity by removal of N- and O-linked oligosaccharides. Therefore, the dual LH- and FSH-like activities of eCG can be clearly separated by removal of either the N-linked oligosaccharide on the $\alpha$-subunit or CTP-associated O-linked oligosaccharides from its $\beta$-subunit. The glycoresidues seem to play crucial roles fer biological activities. The tethered-eCG was effciently secreted and showed similar LH-like activity to the dimeric eCG $\alpha$/ $\beta$ and native eCG. FSH-like activity of the tethered-eCG was also shown similarly in comparison with the native and wild type eCG $\alpha$/ $\beta$. Our data for the first time suggest that the tethered-eCG can be expressed efficiently and the produced product by the CHO-Kl cells is fully LH- and FSH-like activities in rat in vitro bioassay system. Our results also suggest that this molecular can imply particular models ot FSH-like activity not LH-like activity in the eCG. Taken together, these data indicate that the constructs of tethered molecule will be useful in the study of mutants that affect subunit association and/or secretion.

• Korean Journal of Clinical Pharmacy
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• v.30 no.1
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• pp.1-10
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• 2020

Objective: The aim of the study was to perform a meta-analysis of randomized clinical trials to compare the clinical efficacy and safety between combination of cyclin-dependent kinase (CDK) 4/6 inhibitors with aromatase inhibitors (AIs) and AIs alone in patients with hormone receptor+/human epidermal growth factor receptor type2-(HR+/HER2-) advanced breast cancer. Methods: Published clinical studies were identified through electronic database searches until February 2019. Literature qualities were assessed by the Scottish Intercollegiate Guidelines Network Checklist. Key endpoints of efficacy were progression-free survival (PFS), objective response rate (ORR), and clinical benefit (CB). Endpoints of safety were adverse events (AEs) (neutropenia, leukopenia, any grade 3/4 AEs, and serious AEs) and on-treatment death. Meta-analysis was performed using the RevMan 5.3 software. Results: The selected five studies were evaluated as "good" in quality assessment. Compared to AIs alone, the combination therapy significantly improved PFS (pooled hazard ratio=0.55; 95% confidence interval (CI) 0.49-0.62), ORR (odds ratio=1.78; 95% CI=1.49-2.13), and CB (odds ratio=1.86; 95% CI=1.51-2.28). The prevalence of AEs was significantly higher in the combination group than in the AIs alone group. On-treatment death was greater in the combination group than in the AIs alone group, although insignificant. Conclusion: The combination therapy of CDK4/6 inhibitors with AIs was more effective for the treatment of HR+/HER2- advanced breast cancer, but less safe than AIs alone. The combination therapy should be effectively managed through patient monitoring, and further studies are needed to reduce AEs in the combination therapy of CDK4/6 inhibitors with AIs.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.6
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• pp.903-910
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• 2016

In this study, the expression level of estrogen receptor in an ovariectomized rat model was effectively enhanced by MS-10, Cirsium japonicum and Thymus vulgaris extract complex, in a reversible manner. MS-10 plays a positive role in enhancing estrogen activity at low concentrations, leading to improved women's health. In order to determine whether or not MS-10 improves menopausal symptoms clinically, a randomized, double-blinded, and placebo-controlled clinical study was carried out on 62 middle-aged women treated with 500 mg of MS-10 or placebo daily for 12 weeks. Clinical menopausal symptoms were evaluated by Kupperman's index (KI) detecting various menopausal symptoms, including hot flushes, parenthesis, insomnia, nervousness, melancholia, dizziness, fatigue, rheumatic pain, palpitations, formication, and headaches. Total KI score decreased significantly by about 18% upon ingestion of MS-10. Colpoxerosis, a main symptom of menopause, was significantly reduced by about 21% upon ingestion of MS-10 in contrast to placebo. In addition, reduction of insulin-like growth factor-1 with age was improved by over 10% upon ingestion of MS-10, whereas there were no significant difference with placebo. No side effects appeared after treatment with MS-10. Thus, MS-10 can be suggested as a plausible natural substance for improving women's health.

• Development and Reproduction
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• v.10 no.2
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• pp.97-103
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• 2006

Vitellogenin(Vg) is a sex specific serum protein present in sexually maturing female blood of oviparous vertebrates. Estrogen($E_2$) is a main inducer of hepatic Vg synthesis. We investigated the effects of androgen and growth hormone(GH) on regulation of Vg and estrogen receptor(ER) genes in Japanese eel. Immature eels($200{\sim}250\;g$) were given a single injection of $E_2(5{\sim}5,000\;{\mu}g/kg\;bw)$ alone, or in combination with eel recombinant GH(eGH, $1{\sim}10\;{\mu}g/kg$) or methyltestosterone(MT, $1{\sim}5\;mg/kg$) and sacrificed 10 days after the hormone treatments. Expression levels of ER and Vg genes from the liver were determined by means of reverse transcription and polymerase chain reaction(RT-PCR). Administration of $E_2$ stimulated Vg gene expression in a dose dependent manner. Levels of Vg mRNA after the injection of $E_2(500\;{\mu}g/kg)$ with MT(5mg/kg) or eGH($10\;{\mu}g/kg$) were much higher than in that of $E_2$ alone($500\;{\mu}g/kg$). Whereas, injection of either vehicle, eGH ($10\;{\mu}g/kg$) or MT(5mg/kg) alone did not induce the expression of Vg gene in the liver. ER mRNA was detected from the fish treated with vehicle alone. $E_2$ injection($5{\sim}500\;{\mu}g/kg\;bw$) increased this ER expression but dose dependent response was not clear. Addition of MT(5mg/kg) or eGH($10\;{\mu}g/kg$) did not affect $E_2-stimulated$ ER mRNA expression. This study confirms the necessity of $E_2$ as the primary factor for Vg gene expression and requirement of additional hormones such as MT or GH for the full expression of Vg mRNA, and suggests that the additive effect of MT or GH on Vg gene expression would be mediated by some unknown factors other than ER.

• Clinical and Experimental Pediatrics
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• v.48 no.3
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• pp.337-341
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• 2005

Thyrotropin receptor(TSHR) mutations must be considered when congenital hyperthyroidism has persisted, but there has been no evidence for autoimmunity. TSHR mutations leading to constitutive activation of the thyroid gland were identified as the molecular cause of autosomal dominant nonautoimmune hyperthyroidism and sporadic congenital hyperthyroidism. We report two cases of hyperthyroidism caused by germline TSHR mutation who presented with exessive sweating and no evidence of autoimmune thyroid disease. They were brothers and their mother had undergone thyroidectomy because of hyperthyroidism. Direct sequencing of the polymerase chain reaction-amplified exon 10 of the TSHR genomic DNA revealed a transition of GCT to GTT, resulting in an exchange of alanine 627 to valine in the patients and their mother. This might be a novel mutation or polymorphism, but we did not perform any functional gene study. But considering the clinical profiles, we can conclude that hyperthyroidism of these two brothers might come from the point mutation described above.

• Journal of Ginseng Research
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• v.27 no.3
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• pp.93-97
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• 2003

Alternative or complementary medicine plays an important role in health care system. Ginseng, being one of the most popular oriental herbs, is believed to contain various steroid hormone activity. Ginseng has been demonstrated pharmacological effect in the cardiovascular, endocrine, central nervous, and immune system. Our objective was to study that total saponin might mediate some of their actions by binding to the steroid hormone receptor, as they share many of the actions of steroid hormone in various physiological system. Using total saponin from Panax Ginseng, we have studied the possibility of total saponin being a potential estrogen receptor, androgen receptor, and retinoic acid receptor ligand. Total saponin activated the transcription of both the estrogen and androgen responsive luciferase reporter plasmids at a concentration of 100$\mu\textrm{g}$/ml in COS cells transiently transfected with the corresponding receptor and hormone responsive receptor plasmids. And total saponin caused a concentration-dependent stimulation of estrogen receptor. Total saponin increased the expression of estrogen responsive c-fos proto-oncogene at the protein level in MCF7 cells at 24 h treatment as examined by Western analysis. The c-fos induction was used as a specific marker of estrogen responsiveness. This activation was inhibited by the specific estrogen receptor antagonist, ICI 182,780. However, total saponin failed to activate the retinoic acid receptor in COS cells transiently transfected with the corresponding receptor and retinoic acid responsive reporter plasmids. These results show that total saponin is capable of activating estrogen and androgen receptors.