• Korean Journal of Veterinary Research
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• v.32 no.2
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• pp.165-173
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• 1992

The present study was carried out to investigate the effects of dopaminergic drugs and the role of specific dopamine(DA) receptors on the release of TSH, $T_4$ and $T_3$. Serum TSH levels (cold-induced, $4{^{\circ}C}$) were determined using RIA(radioimmunoassay) at 30 min after administration of dopamine agonists and antagonists. Serum $T_4$ and $T_3$ levels were detected after these dopaminergic drugs were administered subcutaneously twice a day for a week. The results of the study are summarized as follows : Apomorphine, a nonspecific DA receptor agonist, produced a dose-depedent decrease in serum TSH, $T_4$ and $T_3$ levels. However, only low doses (0.3, 1.0mg/kg) of SKF38393, a specific $D_1$-receptor agonist, produced a decrease in serum lelvels of TSH. I,Y171555, a specific $D_2$-receptor agonist, produced a dose dependent decrease in serum TSH, $T_4$ and $T_3$ levels. However, SCH23390, a specific $D_1$-receptor antagonist, produced a decrease except in serum T levels which were increased dose dependently. High doses (1.0, 3.0mg/kg) of sulpiride, a specific $D_2$-receptor antagonist, made a increase in the serum levels of TSH and $T_3$. The effects of dopaminergic drugs in serum TSH and $T_4$ levels was potentiated by the pretreatment of apomorphine. The overall results of this study suggest that the regulation of TSH, $T_4$ and $T_3$ secretion were mediated via specific $D_1$ and $D_2$ receptor.

• Animal Bioscience
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• v.37 no.8
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• pp.1377-1386
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• 2024

Objective: Embryonic interferon-tau (IFNT) and progesterone affect expression of interferon-stimulated genes (ISGs), progesterone receptor (PGR) and progesterone-induced blocking factor (PIBF) in the ovine thyroid. Methods: Thyroids of ewes were sampled at day 16 of nonpregnancy, days 13, 16, and 25 of pregnancy, and real-time quantitative polymerase chain reaction assay, western blot and immunohistochemistry were used to detect expression of ISGs, PGR, and PIBF. Results: Free ISG15 protein was undetected, but ISG15 conjugated proteins upregulated at day 16 of pregnancy, and expression levels of ISG15 conjugated proteins, PGR isoform (70 kDa), PIBF, interferon-gamma-inducible protein 10 and myxovirusresistance protein 1 peaked, but expression level of signal transducer and activator of transcription 1 was the lowest at day 16 of pregnancy. In addition, the expression levels of PGR isoform (70 kDa) and signal transducer and activator of transcription 1 (STAT1) decreased, but levels of PGR isoform (43 kDa), 2',5'-oligoadenylate synthetase, IP-10 and MX1 increased at day 25 of pregnancy comparing with day 16 of the estrous cycle. Conclusion: Early pregnancy affects expression of ISGs, PGR, and PIBF in maternal thyroid through IFNT and progesterone, which may regulate thyroid autoimmunity and thyroid hormone secretion in ewes.

• BMB Reports
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• v.47 no.11
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• pp.643-648
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• 2014

Stanniocalcin (STC), a glycoprotein hormone originally discovered in fish, has been implicated in calcium and phosphate homeostasis. While fishes and mammals possess two STC homologs (STC1 and STC2), the physiological roles of STC2 are largely unknown compared with those of STC1. In this study, we identified Ran-binding protein M (RanBPM) as a novel binding partner of STC2 using yeast two-hybrid screening. The interaction between STC2 and RanBPM was confirmed in mammalian cells by immunoprecipitation. STC2 enhanced the RanBPM-mediated transactivation of liganded androgen receptor (AR), but not thyroid receptor ${\beta}$, glucocorticoid receptor, or estrogen receptor ${\beta}$. We also found that AR interacted with RanBPM in both the absence and presence of testosterone (T). Furthermore, we discovered that STC2 recruits RanBPM/AR complex in T-dependent manner. Taken together, our findings suggest that STC2 is a novel RanBPM-interacting protein that promotes AR transactivation.

• Animal Bioscience
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• v.35 no.8
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• pp.1184-1194
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• 2022

Objective: High concentrate diets are widely used to satisfy high-yielding dairy cows; however, long-term feeding of high concentrate diets can cause subacute ruminal acidosis (SARA). The endocrine disturbance is one of the important reasons for metabolic disorders caused by SARA. However, there is no current report about thyroid hormones involved in liver metabolic disorders induced by a high concentrate diet. Methods: In this study, 12 mid-lactating dairy cows were randomly assigned to HC (high concentrate) group (60% concentrate of dry matter, n = 6) and LC (low concentrate) group (40% concentrate of dry matter, n = 6). All cows were slaughtered on the 21st day, and the samples of blood and liver were collected to analyze the blood biochemistry, histological changes, thyroid hormones, and the expression of genes and proteins. Results: Compared with LC group, HC group showed decreased serum triglyceride, free fatty acid, total cholesterol, low-density lipoprotein cholesterol, increased hepatic glycogen, and glucose. For glucose metabolism, the gene and protein expression of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase 1 in the liver were significantly up-regulated in HC group. For lipid metabolism, the expression of sterol regulatory element-binding protein 1, long-chain acyl-CoA synthetase 1, and fatty acid synthase in the liver was decreased in HC group, whereas carnitine palmitoyltransferase 1α and peroxisome proliferator activated receptor α were increased. Serum triiodothyronine, thyroxin, free triiodothyronine (FT3), and hepatic FT3 increased in HC group, accompanied by increased expression of thyroid hormone receptor (THR) in the liver. Conclusion: Taken together, thyroid hormones may increase hepatic gluconeogenesis, β-oxidation and reduce fatty acid synthesis through the THR pathway to participate in the metabolic disorders caused by a high concentrate diet.

• Journal of Microbiology and Biotechnology
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• v.33 no.10
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• pp.1351-1360
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• 2023

Endocrine-disrupting chemicals (EDCs) are compounds that disturb hormonal homeostasis by binding to receptors. EDCs are metabolized through hepatic enzymes, causing altered transcriptional activities of hormone receptors, and thus necessitating the exploration of the potential endocrine-disrupting activities of EDC-derived metabolites. Accordingly, we have developed an integrative workflow for evaluating the post-metabolic activity of potential hazardous compounds. The system facilitates the identification of metabolites that exert hormonal disruption through the integrative application of an MS/MS similarity network and predictive biotransformation based on known hepatic enzymatic reactions. As proof-of-concept, the transcriptional activities of 13 chemicals were evaluated by applying the in vitro metabolic module (S9 fraction). Identified among the tested chemicals were three thyroid hormone receptor (THR) agonistic compounds that showed increased transcriptional activities after phase I+II reactions (T3, 309.1 ± 17.3%; DITPA, 30.7 ± 1.8%; GC-1, 160.6 ± 8.6% to the corresponding parents). The metabolic profiles of these three compounds showed common biotransformation patterns, particularly in the phase II reactions (glucuronide conjugation, sulfation, GSH conjugation, and amino acid conjugation). Data-dependent exploration based on molecular network analysis of T3 profiles revealed that lipids and lipid-like molecules were the most enriched biotransformants. The subsequent subnetwork analysis proposed 14 additional features, including T4 in addition to 9 metabolized compounds that were annotated by prediction system based on possible hepatic enzymatic reaction. The other 10 THR agonistic negative compounds showed unique biotransformation patterns according to structural commonality, which corresponded to previous in vivo studies. Our evaluation system demonstrated highly predictive and accurate performance in determining the potential thyroid-disrupting activity of EDC-derived metabolites and for proposing novel biotransformants.

• Korean Journal of Veterinary Research
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• v.39 no.6
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• pp.1073-1080
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• 1999

Previous studies suggested that the inhibition of thyroxine ($T_4$) release by ${\alpha}_1$-adrenoceptor and muscarinic receptor stimulation results in activated protein kinase C (PKC) from mouse and guinea pig thyroids. In the present study, the effect of carbachol, methoxamine, phorbol myristate acetate (PMA), and R59022 on the release of $T_4$ from the mouse, rat, and guinea pig thyroids was compared to clarify the role of PKC in the regulation of the release of $T_4$. The thyroids were incubated in the medium containing the test agents, samples of the medium were assayed for $T_4$ by EIA kits. Forskolin, an adenylate cyclase activator, chlorophenylthio-cAMP sodium, a membrane permeable analog of cAMP, and isobutyl-methylxanthine, a phosphodiesterase inhibitor, like TSH (thyroid stimulating hormone), enhaced the release of $T_4$ from the mouse, rat, and guinea pig thyroids. Methoxamine, an ${\alpha}_1$-adrenoceptor agonist, inhibited the TSH-stimulated release of $T_4$ in mouse, but not rat and guinea pig thyroids. In contrast, carbachol, a muscarinic receptor agonist, inhibited the release of $T_4$ in guinea pig, but not mouse and rat thyroids. These inhibition were reversed by prazosin, an ${\alpha}_1$-adrenoceptor antagonist or atropine, a muscarinic antagonist or $M_1$- and $M_3$-muscarinic antagonists, in mouse or guinea pig thyroids. In addition, staurosporine, a PKC inhibitor, reversed methoxamine or carbachol inhibition of TSH stimulation. Furthermore, PMA, a PKC activator, and R59022, a diacylglycerol (DAG) kinase inhibitor, inhibited the TSH-stimulated release of $T_4$ in mouse, rat, and guinea pig thyroids. These inhibition were blocked by staurosporine. These findings suggest that the activation of receptor or DAG inhibits TSH-stimulated $T_4$ release through a PKC-dependent mechanism in thyroid gland.

• Journal of Nutrition and Health
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• v.24 no.4
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• pp.356-365
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• 1991

$L-Triiodothyronine(T_3)$ binding to purified plasma membrane and to isolated nuclei from the same liver in obese(ob/ob) mice and their lean littermates was examined. The maximal binding capacity(Bmax) for $T_3$ receptor of liver nuclei, as compared to lean control, was significantly lower in the obese mouse$(obese 527{\pm}80fmol/mg\;DNA ; lean 883{\pm}62fmol/mg\;DNA)$, without an apparent difference in dissociation constant(Kd). The finding that obese mice have fewer liver nuclear $T_3$ receptors confirms previous reports. The Bmax and Kd of liver plasma membrane $T_3$ receptor were not significantly different between obese and lean mouse, which suggests no defect to be occurring in the function of the plasma membrane $T_3$ receptor and reinforces the view that the peripherally impaired thyroid hormone action in obese mice is a post plasma membrane receptor event. These results further support the hypothesis that the major defect of the thyroid hormone metabolism in genetic obesity occurs at the level of the nuclear receptor.

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 2003.05a
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• pp.180-180
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• 2003

Transcript profiling is a particularly valuable tool in the field of steroid receptor biology, as these receptors are ligand-activated transcription factors and therefore exert their initial effects through altering gene expression in responsive cells. Also, an increased awareness of endocrine disrupting chemicals (EBCs) and their potential to affect wildlife and humans has produced a demand for practical screening methods to identify endocrine activity. Here we developed an in-house cDNA microarray, named KISTCHIP-400, with 401 clones, hormone related genes, factors, and ESTs, based on public database and research papers. Theses clones contained estrogen, androgen, thyroid hormone St receptors, sex hormone signal transduction ＆ regulation, c-fos, c-myc, ps2 gene, metabolism related genes etc. And to validate the KISTCHIP-400, we investigated gene expression profiles with reference hormones, 10$\^$-8/ M 17be1a-estradiol, 10$\^$-7/ M testosterone, 10$\^$-7/ M progesterone, and thyroxin in MCF-7 cell line. Although it is in first step of validation, low doses and combinations of EDCs need to be tested. Our preliminary results that indicate the developed microarray may be a useful laboratory tool for screening EDCs and elucidating endocrine disrupting mechanism.

• Childhood Kidney Diseases
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• v.25 no.1
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• pp.40-43
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• 2021

Enuresis is intermittent urinary incontinence during sleep at night in children aged 5 years or older. The main pathophysiology of enuresis involves nocturnal polyuria, abnormal sleep arousal, and low functional bladder capacity. In rare cases, enuresis is an early symptom of endocrine disorders such as diabetes or thyroid disorders. Herein, we report a case of a 12-year-old girl with enuresis as a rare initial presentation of Graves' disease. She complained of nocturnal enuresis from a month before visiting our clinic. She also complained of urinary frequency, headache, and weight loss. On physical examination, she had tachycardia, intention tremors, and a diffuse goiter on her anterior neck with bruit on auscultation. Her thyroid function test results revealed hyperthyroidism, and Graves' disease was diagnosed as the thyroid stimulating hormone receptor autoantibody was positive. After treatment for Graves' disease with methimazole, symptoms of enuresis resolved within 2 weeks as she became clinically and biochemically euthyroid. In children with secondary enuresis, Graves' disease should be considered as a differential diagnosis, and signs of hyperthyroidism should be checked for carefully.

• The Korea Journal of Herbology
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• v.33 no.4
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• pp.77-85
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• 2018

Objective : This study was intended to examine the effects of water extract of Prunellae Spica (PS), which is a herb with 'cold' nature based on hot and cold theory of traditional Korean medicine. Methods : Hyperthyroidism was induced in SD rats by LT4 (0.5 mg/kg, i.p.) daily for four weeks. After 2 weeks of LT4 injection, rats were divided randomly into four groups; normal, LT4-induced hyperthyroid control, PS extract (500 mg/kg, p.o.)-treated group, and propylthiouracil (PTU, 10 mg/kg, s.c.)-treated positive group. After 2 weeks of drug treatment, all rats were sacrificed and harvested blood samples and thyroid tissues. The changes of body weight, food and water intake, and body temperature were measured weekly. Serological markers were analyzed in sera using an enzyme-based assay, and thyroid tissues were stained with Hematoxylin & Eosin (H&E). Brain and dorsal root ganglion (DRG) tissues were isolated and analyzed the expression of transient receptor potential (TRP) channels by Western blot. Results : PS extract administration attenuated the loss of body weight and the increase of body temperature in LT4-induced hyperthyroidism rats. PS extract increased the level of thyroid stimulating hormone (TSH) and decreased tiiodothyronine (T3) and tetraiodothyronine (T4). In action mechanism, PS extract regulated the expression of transient receptor potential channel subfamily V member 1 (TRPV1) and transient Receptor Potential channel subfamily M member 8 (TRPM8), the thermoregulators. Conclusion : To conclude, PS extract can improve the symptoms of hyperthyroidism through regulation of the thyroid hormones imbalance and thermoregulation via TRP channels.