• The Korean Journal of Physiology and Pharmacology
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• v.19 no.5
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• pp.435-440
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• 2015

This study aimed to investigate the effect of pituitary adenylate cyclase-activating peptide (PACAP) on the pacemaker activity of interstitial cells of Cajal (ICC) in mouse colon and to identify the underlying mechanisms of PACAP action. Spontaneous pacemaker activity of colonic ICC and the effects of PACAP were studied using electrophysiological recordings. Exogenously applied PACAP induced hyperpolarization of the cell membrane and inhibited pacemaker frequency in a dose-dependent manner (from 0.1 nM to 100 nM). To investigate cyclic AMP (cAMP) involvement in the effects of PACAP on ICC, SQ-22536 (an inhibitor of adenylate cyclase) and cell-permeable 8-bromo-cAMP were used. SQ-22536 decreased the frequency of pacemaker potentials, and cell-permeable 8-bromo-cAMP increased the frequency of pacemaker potentials. The effects of SQ-22536 on pacemaker potential frequency and membrane hyperpolarization were rescued by co-treatment with glibenclamide (an ATP-sensitive $K^+$ channel blocker). However, neither $N^G$-nitro-L-arginine methyl ester (L-NAME, a competitive inhibitor of NO synthase) nor 1H-[1,2,4]oxadiazolo[4,3-${\alpha}$]quinoxalin-1-one (ODQ, an inhibitor of guanylate cyclase) had any effect on PACAP-induced activity. In conclusion, this study describes the effects of PACAP on ICC in the mouse colon. PACAP inhibited the pacemaker activity of ICC by acting through ATP-sensitive $K^+$ channels. These results provide evidence of a physiological role for PACAP in regulating gastrointestinal (GI) motility through the modulation of ICC activity.

• Clinical and Experimental Reproductive Medicine
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• v.39 no.3
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• pp.95-106
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• 2012

It has been revealed that multiple cohorts of tertiary follicles develop during some animal estrous cycle and the human menstrual cycle. To reach developmental competence, oocytes need the support of somatic cells. During embryogenesis, the primordial germ cells appear, travel to the gonadal rudiments, and form follicles. The female germ cells develop within the somatic cells of the ovary, granulosa cells, and theca cells. How the oocyte and follicle cells support each other has been seriously studied. The latest technologies in genes and proteins and genetic engineering have allowed us to collect a great deal of information about folliculogenesis. For example, a few web pages (http://www.ncbi.nlm. nih.gov; http://mrg.genetics.washington.edu) provide access to databases of genomes, sequences of transcriptomes, and various tools for analyzing and discovering genes important in ovarian development. Formation of the antrum (tertiary follicle) is the final phase of folliculogenesis and the transition from intraovarian to extraovian regulation. This final step coordinates with the hypothalamic-pituitary-ovarian axis. On the other hand, currently, follicle physiology is under intense investigation, as little is known about how to overcome women's ovarian problems or how to develop competent oocytes from in vitro follicle culture or transplantation. In this review, some of the known roles of hormones and some of the genes involved in tertiary follicle growth and the general characteristics of tertiary follicles are summarized. In addition, in vitro culture of tertiary follicles is also discussed as a study model and an assisted reproductive technology model.

• Animal cells and systems
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• v.4 no.2
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• pp.173-179
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• 2000

Evidence suggested that atypical antipsychotics (APs) such as clozapine show less side effects than those of typical APs such as haloperidol and sulpiride. However, little is known about chronic effects of these drugs on changes in gonadotropin releasing hormone (GnRH) mRNA expression and luteinizing hormone (LH) immunoreactivity. Male rats were divided into water-, haloperidol-, sulpiride-, and clozapine-treated groups, and these drugs were administered orally for 4 weeks. The changes in the expression of GnRH mRNA and the LH immunoreactivity were determined in the hypothalamus and pituitary, respectively, using in situ hybridization and immunohistochemistry. GnRH mRNAs were clearly expressed in the water-treated control vats. This was significantly reduced by the chronic treatments with the typical APs, especially with haloperidol, but not with atypical APs clozapine. Likewise, LH immunoreactivity was clearly stained in the control group. While its immunoreativity was significantly reduced by the chronic APs treatments, clozapine treatment showed only slight attenuation. The results show that the atypical APs clozapine has less side effects in the gonadal function than the typical APs haloperidol and the sulpiride. These results suggest that clozapine is a safer drug than the typical APs, at least in the reproductive system.

• Clinical and Experimental Reproductive Medicine
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• v.7 no.1_2
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• pp.3-10
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• 1980

Pituitary gonadotropes, as target cells, exhibit cyclic changes in terms of LH and FSH release in synchrony with the estradiol levels. The ultimate release is determined by the relative size of the two pools of gonadotropins, which is regulated by the two controllers: LH-RH and estradiol. LH-RH appears to serve as a primary drive on the gonadotrope, stimulating gonadotropin synthesis, storage, and release. Estradiol amplifies the action of LH-RH and induces the development of a self-priming effect of LH-RH except that it impedes LH-RH mediated gonadotropin release. Negative and positive feedback action of estradiol is revealed to operate by different mechanisms. The pituitary capacity increases severalfold from early to late follicular phase, which is considered to be prerequisite for the development of mid-cycle surge. CNS-hypothalamic dopamine, norepinephrine, and prostaglandins, as well as LH-RH, are involved in the negative and positive feedback effects of estradiol. The possible mechanisms in the triggering of LH-RH release for the initiation of midcycle LH-RH surge are considered.

• Proceedings of the Korean Biophysical Society Conference
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• 1999.06a
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• pp.58-58
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• 1999

The paraventricular nucleus (PVN) is a complex structure comprised of several different populations of cells divided into two main groups, the magnocellular (type I) neurons which secrete vasopressin and oxytocin and the parvocellular (type II) neurons which regulate hormone secretion from the anterior pituitary.(omitted)

• Journal of Life Science
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• v.22 no.9
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• pp.1243-1253
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• 2012

The production and secretion of growth hormone (GH) in the anterior pituitary gland can be induced by several natural products to control cell proliferation, differentiation, and migration. To investigate whether Chungkookjang (CKJ) produced by the fermentation process affects GH-related metabolism, the secretion and the response of GH were observed in pituitary cells and GH target cells. Among six CKJs manufactured by different strains of glycine max, only three CKJs, including Daewon (DW), Daepung (DP), and Taegwang (TG), induced GH secretion from GH3 cells at 5.0 mg/ml concentration. There were no significant changes detected in the viability of any of the cells treated with these CKJs. In addition, the increase in GH secretion from the GH3 cells was dependent on the concentration of the three types of CKJs. The proliferation of cell lines, including MG63 and HepG2 cells, that originated from those derived from the GH target organs was significantly activated by treatment with the GH-containing conditional medium (GCM) harvested from the three CKJ-treated GH3 cells, although their induction rate was different from each other. In these cells, p-STAT5 was maximally translocated into the nucleus of MG63 cells 30 min after DW treatment, while it was translocated in HepG2 cells at 60 min. These results suggest that these three types of CKJ could enhance the secretion of GH, as well as the GCM-derived response, in the two target organs.

• BMB Reports
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• v.40 no.6
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• pp.966-972
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• 2007

Pituitary tumor transforming gene (PTTG1) is widely detected in many tumors. Increasing evidence reveals that PTTG1 is associated with cell proliferation, cellular transformation and apoptosis. However, the functions of PTTG1, especially its role in DNA damage-induced apoptosis, remain largely unclear. In this report, we used UV irradiation to induce apoptosis in HeLa cells to examine the role of PTTG1 in UV-induced apoptosis by RNAi-mediated knockdown and overexpression of PTTG1. RNAi-mediated knockdown of PTTG1 expression increased and overexpression of PTTG1 decreased the UV-induced apoptosis. Furthermore, UV irradiation decreased PTTG1 mRNA and protein expression. These effects were found to be mediated by JNK pathway. Therefore, PTTG1 had an important anti-apoptotic role in UV-induced apoptosis and this role was mediated by JNK pathway. These results may provide important information for understanding the exact role and the regulation mechanism of PTTG1 in UV-induced apoptosis.

• IMMUNE NETWORK
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• v.6 no.1
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• pp.6-12
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• 2006

Background: The Hypothalamo-Pituitary-Adrenal (HPA) axis is an important regulator for the body's stress response. As a primary stress responsive system, HPA-axis secretes various neurotransmitters, hormones, and cytokines, which regulates the immune system. Natural killer (NK) cell which is plays an important role in the innate immune response, is specially decreased their numbers and loose cytolytic activity in response to stress. However, the effect of HPA-axis secreted proteins on NK cell activity has not been defined. Herein, we studied the effect of adrenal secreted adiponectin on NK cell cytotoxicity. Adiponectin which is well-known metabolic control protein, plays important roles in various diseases, including hypertension, cardiovascular diseases, inflammatory disorders, and cancer. Methods: Signal sequence trap was used to find stress novel secretory protein from HP A-axis. Selected adiponectin was treated mouse mature primary NK cells and then examined the effect of adiponectin to NK cell cytotoxicity and cytokine expression level. Results: We found that adiponectin which is secreted from adrenal gland, suppress IL-2 induced NK cell cytotoxicity. And also investigated cytolytic cytokines are suppressed by adiponectin. Conclusion: These data suggest that adiponectin inhibites NK cell cytotoxicity via suppression of cytotoxicity related target gene.

• BMB Reports
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• v.40 no.6
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• pp.979-985
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• 2007

Induction of growth hormone (GH) by Glycyrrhizae Radix (GR), one of the most popular herbal medicine, and its major ingredients were studied in rat pituitary cells in vitro and in vivo assay. The MeOH extract and the n-hexane (HX) fraction of GR induced rat GH (rGH) release up to 1.89 times ($0.34{\pm}0.04 nM$) and 4.59 times ($0.83{\pm}0.03 nM$), compared to the basal level (p < 0.05). Among many ingredients isolated and purified from GR both glycyrrhetinic acid and glycyrrhizin induced significantly rGH release compared to the control (p < 0.05). After an intravenous injection of rat growth hormone releasing hormone (rGHRH) ($10{\mu}g$/kg) as positive control, in SD rats, $T_{max}$ of plasma rGH level was 10 min, $C_{max}$ was $3.84{\pm}0.01 nM$ (n = 3), and enhanced plasma rGH level returned to the baseline in 90 min. Both $AUC_{0-90}$ (area under the curve) of plasma rGH level after HX fraction and that after rGHRH administration were increased significantly from the basal level, respectively (p < 0.01). In conclusions, HX fraction is the most active fraction of MeOH extract of GR in rGH induction.

• Journal of Life Science
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• v.10 no.1
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• pp.22-36
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• 2000

The mammary gland contains a subpopulation of epithelial cells with large proliferative potentials which are the likely targets for carcinogens. These clonogenic cells can proliferate and differentiate into functional glandular structures. Multicellular secretory alveolar units (AU) develop from these clonogens in grafts of monodispersed rat mammary epithelial cells (RMEC) in gland-free mammary fat pads in intact recipient F344 rats co-grafted with mammotropic hormone-secreting pituitary tumors (MtT F4). Multicellular nonsecretory ductal units (DU) develop in grafts of monodispersed RMEC in gland-free fat pads in adrenalectomized recipient WF rats co-grafted with MtT W10. However, this effect were reversed by hydrocortisone replacement therapy. RMEC were isolated from appropriate donor rats as monodispersed mixed cells or, alternatively, RNA＋ cells were sorted by flow cytometry of mixed RMEC stained with FITC-RNA and PE-anti-Thy-1.1 monoclonal antibody. We grafted mixed or sorted PNA+ cells in gland-free mammary fat pads in recipient rats that were endocrinologically manipulated to induce AU or DU. Cells were also isolated from these AU or DU as mixed or sorted RNA＋ cells and sub-transplanted in recipient rats treated appropriately to induce AU or DU, respectively. Cells obtained from AU in grafts gave rise to clonal AU and from DU in grafts to DU on sub-transplantation in appropriate recipients. When adrenalectomized recipient WF rats co-grafted with MtT W10 received daily subcutaneous injections of hydrocortisone for periods of 21 days following the PHA＋ cell transplantation, AU, instead of DU, were developed. The histologies of these secondary AU and DU were not different from those of the primary AU and DU. Casein and laminin proteins were demonstrated by immunocytochemical staining of primary and secondary AU. Electron micrographs also demonstrated that AU were composed of secretory cells with milk protein in the cytoplasm. DU were composed of little or non-secretory ductal epithelial cells. These AU and DU also secreted large amounts of lipids. Clonogenic cells were more common in DU than in AU. Thus, AU and DU contain persistent subpopulations of clonogenic stem-like cells.