• Clinical and Experimental Reproductive Medicine
• /
• v.23 no.3
• /
• pp.269-275
• /
• 1996

Biosynthesis and secretion of anterior pituitary hormones are under the control of specific hypothalamic stimulatory and inhibitory factors. Among them, Growth Hormone Releasing Hormone (GHRH) is the major stimulator of pituitary somatotrophs activating GH gene expression and secretion. Human GHRH is a polypeptide of 44 amino acids initially isolated from pancreatic tumors, and the gene for the hypothalamic form of GHRH is organized into 5 exons spanning over 10 kilobases (kb) on genomic DNA and encodes a messenger RNA of 700-750 nucleotides. Several neuropeptides classically associated with the hypothalamus have been found in the extrahypothalamic regions, suggesting the existence of novel sources, targets and functions. GHRH-like immunoreactivity has been found in several peripheral sites, including placenta, testis, and ovary, indicating that GHRH may also have regulatory roles in peripheral reproductive organs. Furthermore, higher molecular weight forms of the GHRH transcripts were identified from these organs (1.75 kb in testis; 1.75 and >3 kb in ovary). These tissue-specific expression of GHRH gene suggest the existence of unique regulatory mechanism of GHRH expression and function in these organs. In fact, placenta-specific and testis-specific promoters for GHRH transcripts which are located in about 10 kb upstream region of hypothalamic promoter were reported. The use of unique promoters in extrahypothalamic sites could be refered in a different control of GHRH gene and different functions of the translated products in these tissues. Somatotrophs and lactotrophs have been thought to be derived from a common bipotential progenitor, the somatolactotrophs, which give origins to either phenotypes. Although the precise mechanism responsible for the lactotroph differentiation in the anterior pituitary gland has not been yet clalified, there are several candidators for the generation of lactotrophs. In human, the presence of GHRH peptides with different size from authentic hypothalamic form in the normal anterior pituitary and several types of adenoma were demonstrated. Recently our group found the existence of immunoreactive GHRH and its transcript from the normal rat anterior pituitary (gonadotroph> somatotroph> lactotroph), and the GHRH treatment evoked the increased proliferation rate of anterior pituitary cells in vitro. The transgenic mouse models clearly shown that GHRH or NGF overexpression by anterior pituitary cells induced development of pituitary hyperplasia and adenomas particularly GH-oma and prolactinoma. Taken together, we hypothesize that the pituitary GHRH could serve not only as a modulator of hormone secretion but as a paracrine or autocrine regulator of anterior pituitary cell proliferation and differentiation. Interestingly enough, the expression of Pit-1 homeobox gene (the POU class transcription factor) was confined to somatotrophs, lactotrophs and somatolactotrophs in which GHRH receptors are expressed commonly. Concerning the mechanism of somatolactotroph and lactotroph differentiation in the anterior pituitary, we have focused following two possibilities; (1) changes in the relative levels or interactions of both hypothalamic and intrapituitary factors such as dopamine, VIP, somatostatin, NGF and GHRH; (2) alterations of GHRH-GHRH receptor signaling and Pit-1 activity may be the cause of lactotroph differentiation or pituitary hyperplasia and adenoma formation. Extensive further studies will be necessary to solve these complicated questions.

• Journal of Ginseng Research
• /
• v.46 no.1
• /
• pp.62-70
• /
• 2022

Background: Maternal Toxoplasma gondii (T. gondii) infection during pregnancy has been associated with various mental illnesses in the offspring. Ginsenoside Rh2 (GRh2) is a major bioactive compound obtained from ginseng that has an anti-T. gondii effect and attenuates microglial activation through toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway. GRh2 also alleviated tumor-associated or lipopolysaccharide-induced depression. However, the effects and potential mechanisms of GRh2 on depression-like behavior in mouse offspring caused by maternal T. gondii infection during pregnancy have not been investigated. Methods: We examined GRh2 effects on the depression-like behavior in mouse offspring, caused by maternal T. gondii infection during pregnancy, by measuring depression-like behaviors and assaying parameters at the neuronal and molecular level. Results: We showed that GRh2 significantly improved behavioral measures: sucrose consumption, forced swim time and tail suspended immobility time of their offspring. These corresponded with increased tissue concentrations of 5-hydroxytryptamine and dopamine, and attenuated indoleamine 2,3-dioxygenase or enhanced tyrosine hydroxylase expression in the prefrontal cortex. GRh2 ameliorated neuronal damage in the prefrontal cortex. Molecular docking results revealed that GRh2 binds strongly to both TLR4 and high mobility group box 1 (HMGB1). Conclusion: This study demonstrated that GRh2 ameliorated the depression-like behavior in mouse offspring of maternal T. gondii infection during pregnancy by attenuating the excessive activation of microglia and neuroinflammation through the HMGB1/TLR4/NF-κB signaling pathway. It suggests that GRh2 could be considered a potential therapy in preventing and treating psychiatric disorders in the offspring mice of mothers with prenatal exposure to T. gondii infection.

• The Journal of Korean Academy of Prosthodontics
• /
• v.61 no.3
• /
• pp.227-233
• /
• 2023

Tardive dyskinesia is an involuntary neurological movement disorder caused by long-term use of dopamine receptor-blocking drugs leading to dental implications like uncontrolled gnashing and grinding of teeth which in turn imperil the oral rehabilitation procedures as the excessive load increases the risk of prosthesis fracture. A 40-year male with a medical history of tardive dyskinesia visited the hospital to receive oral rehabilitation for missing maxillary anterior teeth. After the oral examination, tooth preparation was done on teeth 13, 15, and 23. After that silicon impression was made and the gypsum cast was digitalized using a desktop scanner and an interim prosthesis was fabricated by milling a resin block. During the try-in, the occlusal one-third of the interim prosthesis was trimmed, and an auto-polymerizing acrylic resin was applied on the occlusal surfaces and inserted in the patient's mouth. Then, the functionally generated path (FGP) of occluding surfaces of opposing arches was traced on the resin surface. When the resin was hardened, the modified interim prosthesis was removed and digitized using an intraoral scanner. The scan image was used in designing the occlusal morphology of definitive prosthesis by modifying the design of the interim prosthesis using the dual scan method. Lastly, a monolithic zirconia prosthesis was fabricated by milling a zirconia block. The definitive prosthesis was delivered reflecting the patient's occlusal scheme. This case report shows that the FGP technique with the dual scan method can help in fabricating fixed prosthesis with harmonious occlusion in a tardive dyskinesia patient.

• Korean Journal of Biological Psychiatry
• /
• v.14 no.4
• /
• pp.232-240
• /
• 2007

Objectives : Vascular endothelial growth factor(VEGF), one of potent cytokines, and its receptors were related with various biological functions and pathological conditions. The purpose of this study was to investigate the changes of serum level of free VEGF, soluble VEGFR-1, and soluble VEGFR-2 after treatment with atypical antipsychotic drug in schizophrenia. Method : The schizophrenic patients were diagnosed with DSM-IV and were prospectively followed up for 4 and 8 weeks. Thirteen schizophrenic patients were evaluated their clinical assessment with serum levels of free VEGF, sVEGFR-1, sVEGFR-2, and positive and negative symptom scale(PANSS) at baseline, 4 weeks, and 8 weeks after treatment with atypical antipsychotic drug. Thirteen normal control subjects were recruited and matched with the patient group by age and sex. Result : The serum level of free VEGF($295.2{\pm}43.7$pg/ml)and sVEGFR-2($8259{\pm}336.7$) at baseline(before treatment) in schizophrenic patients were not significantly different, compared with the control group($199.0{\pm}28.8$ and $8481{\pm}371.9$) respectively. However, the serum level of sVEGFR-1($86.2{\pm}10.3$, p<0.05) was significantly increased in the schizophrenic patients compared with the control group($59.0{\pm}6.4$). After treatment with antipsychotic drug, the serum levels of free VEGF at 4 weeks($338.9{\pm}56.5$) and 8 weeks($309.5{\pm}58.7$) were not significantly, different compared with baseline. But the serum levels of sVEGFR-1 was significantly decreased at 8 weeks ($57.3{\pm}6.3$, p<0.05) after antipsychotic drug treatment. The serum levels of sVEGFR-2 were decreased at 4 weeks ($7761{\pm}403.0$, p<0.05) and 8 weeks($7435{\pm}333.5$, p<0.05) compared with baseline. Conclusion : The decreased serum level of sVEGFR-1 and sVEGFR-2 might be affected by dopaminergic system which was influenced by antipsychotic drug.

• Progress in Medical Physics
• /
• v.9 no.3
• /
• pp.163-173
• /
• 1998

Nuclear medicine emission computed tomography(ECT) can be very useful to diagnose early stage of neuronal diseases and to measure theraputic results objectively, if we can quantitate energy metabolism, blood flow, biochemical processes, or dopamine receptor and transporter using ECT. However, physical factors including attenuation, scatter, partial volume effect, noise, and reconstruction algorithm make it very difficult to quantitate independent of type of SPECT. In this study, we quantitated the effects of attenuation and scatter using brain SPECT and three-dimensional brain phantom with and without applying their correction methods. Dual energy window method was applied for scatter correction. The photopeak energy window and scatter energy window were set to 140ke${\pm}$10% and 119ke${\pm}$6% and 100% of scatter window data were subtracted from the photopeak window prior to reconstruction. The projection data were reconstructed using Butterworth filter with cutoff frequency of 0.95cycles/cm and order of 10. Attenuation correction was done by Chang's method with attenuation coefficients of 0.12/cm and 0.15/cm for the reconstruction data without scatter correction and with scatter correction, respectively. For quantitation, regions of interest (ROIs) were drawn on the three slices selected at the level of the basal ganglia. Without scatter correction, the ratios of ROI average values between basal ganglia and background with attenuation correction and without attenuation correction were 2.2 and 2.1, respectively. However, the ratios between basal ganglia and background were very similar for with and without attenuation correction. With scatter correction, the ratios of ROI average values between basal ganglia and background with attenuation correction and without attenuation correction were 2.69 and 2.64, respectively. These results indicate that the attenuation correction is necessary for the quantitation. When true ratios between basal ganglia and background were 6.58, 4.68, 1.86, the measured ratios with scatter and attenuation correction were 76%, 80%, 82% of their true ratios, respectively. The approximate 20% underestimation could be partially due to the effect of partial volume and reconstruction algorithm which we have not investigated in this study, and partially due to imperfect scatter and attenuation correction methods that we have applied in consideration of clinical applications.

• The Korean Journal of Pharmacology
• /
• v.30 no.1
• /
• pp.29-37
• /
• 1994

Inhibition of the nociceptive Tail Flick Reflex (TFR) was observed with electrical stimulation of the locus coeruleus/subcoeruleus (LC/SC) in the male Sprague - Dawley rats under light anesthesia, and the involved neurotransmitter (s) were characterized. Electrical stimulation of LC/SC induced the analgesia with the stimulation threshold (intensity of the current, given for 100 usec and in 100 Hz frequency, which caused the TF latency longer than 6.5 sec) around 55 uA. Intrathecal administrations of ${\alpha}_2$ antagonist, yohimbine (30 ug) or opioid antagonist, naloxone (20 ug) increased the stimulation threshold by 147% and 123% respectively (from 55 uA to 135 uA,9 and from 54 uA to 123 uA;P0.01, n=5, each). The basal TF latency without stimulation (3.1 sec) was reduced by the antagonists (to 2.5 sec by yohimbine, p<0.05, n=5; to 2.6 sec by naloxone, p<0.1, n=5), vehicle only did not show any effect. Noradrenaline(NA) in the spinal cord superfusates measured with HPLC was increased by the LC/SC stimulation, from 4.18 ng/ml before to 7.74 ng/ml after stimulation (P<0.05, n=10). The result suggest that analgesia induced by LC/SC stimulation is mediated, at least in part, by the noradrenergic system in which ${\alpha}_2$ receptor is involved, as well as the opioid system.

• Journal of Life Science
• /
• v.17 no.2 s.82
• /
• pp.167-173
• /
• 2007

To study the transcriptional mechanisms by which expression of the murine glial cell-derived neurotrophic factor inducible transcription factor (mGIF) gene is regulated, a murine genomic clone was iso-lated using a mGIF cDNA as probe. A 13-kb genomic fragment, which comprises 4-kb upstream of the transcription initiation site was sequenced. The promoter region lacks a TATA box and CAAT box, is rich in G+C content, and has multiple putative binding sites for the transcription factor Spl. The mGIF gene also has consensus sequences for AP2 binding sites. The transcriptional activity of five deletion mutants of a 2.1-kb fragment was analyzed by modulating transcription of the heterologous luciferase gene in the promoterless plasmid pGL2-Basic. All mutants showed significant transcriptional activity in the murine neuroblastoma cell line NB41A3. Transient expression assays suggested the presence of a positive regulator between -213 and -129 while a negative regulator was found in the region between -806 and -214. Relatively strong transcriptional activity was observed in neuronal NB41A3, glial C6 cells and hepatic HepG2, but very weak activity in skeletal muscle C2C12 cells. These findings confirm the tissue-specific activity of the mGIF promoter and suggest that this gene shares structural and functional similarities with the dopamine receptor genes that it regulates.