• The Korean Journal of Physiology and Pharmacology
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• 제12권5호
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• pp.217-223
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• 2008

To directly test if elevated glucocorticoids are required for fasting-induced regulation of growth hormone (GH)-releasing hormone (GHRH), GHRH receptors (GHRH-R) and ghrelin receptors (GHS-R) expression, male rats were bilaterally adrenalectomized or sham operated. After 7 days, animals were fed ad libitum or fasted for 48 h. Bilateral adrenalectomy increased hypothalamic GHRH to 146% and decreased neuropeptide Y (NPY) mRNA to 54% of SHAM controls. Pituitary GHRH-R and GHS-R mRNA levels were decreased by adrenalectomy to 30% and 80% of shamoperated controls. In shamoperated rats, fasting suppressed hypothalamic GHRH (49%) and stimulated NPY (166%) mRNA levels, while fasting increased pituitary GHRH-R (391%) and GHS-R (218%) mRNA levels. However, in adrenalectomized rats, fasting failed to alter pituitary GHRH-R mRNA levels, while the fasting-induced suppression of GHRH and elevation of NPY and GHS-R mRNA levels remained intact. In fasted adrenalectomized rats, corticosterone replacement increased GHRH-R mRNA levels and intensified the fasting-induced decrease in GHRH, but did not alter NPY or GHS-R response. These data suggest that elevated glucocorticoids mediate the effects of fasting on hypothalamic GHRH and pituitary GHRH-R expression, while glucocorticoids are likely not the major determinant in fasting-induced increases in hypothalamic NPY and pituitary GHS-R expression.

• Molecules and Cells
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• 제23권3호
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• pp.331-339
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• 2007

It has been suggested that the structure and function of nuclear receptors are evolutionally conserved. Here, we compare the molecular functions of the nile tilapia (Oreochromis niloticus) small heterodimer partner (nSHP/NR0B2) and the Dosage-sensitive sex reversal AHC critical region on X chromosome gene 1 (nDAX-1/NR0B1) with those of human SHP and DAX-1 (hSHP and hDAX-1, respectively). We found that, upon transient cotransfection of human cells, nDAX-1 repressed the activity of tilapia SF-1 (nSF-1) but not that of human SF-1, although the physical interaction with human SF-1 was retained. Similarly, nSHP repressed the activity of nSF-1, whereas hSHP did not, pointing to divergent evolution of SHP/SF-1 in fish and human. We thus propose that the repressive functions of SHP and DAX-1 have been conserved in fish and mammals although with different transcriptional targets and mechanisms. These differences provide new insights into the physiological diversification of atypical orphan nuclear receptors during vertebrate evolution.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.186.2-186.2
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• 2003

PPARs (peroxisome proliferator activated receptors) are member of nuclear hormone receptors superfamily. Activations of PPARs upon binding with ligands modulate glucose metabolite, differentiation of adipocyte, inflammation response, and so on. Thiazolidinedione analog is one of the potential antidiabetic drug that binds and activates PPAR selectively and enhances insulin sensitivity. In an effort to develop novel and effective antidiabetic thiazolidindione analogs, we have synthesized tetrahydroquinoline and para-substituted benzene-linked thiazolidinedione analogs by coupling reaction of the hydrophobic segments with hydroxybenzylthiazolidinedione.

• Asian-Australasian Journal of Animal Sciences
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• 제22권2호
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• pp.275-281
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• 2009

Modification of thyroid hormone levels has a profound effect on skeletal muscle differentiation, predominantly through direct regulation involving thyroid hormone receptors. Nevertheless, little is known about the regulation of myostatin gene expression in skeletal muscle due to altered concentrations of thyroid hormone. Thus, the goal of our study was to find out whether altered thyroid states could change the gene expression of myostatin, the most powerful inhibitor of skeletal muscle development. A hyperthyroid state was induced in rats by daily injections of L-thyroxine 20 mg/100 g body weight for 14 days, while a hypothyroid state was induced in another group of rats by administering methimazole (0.04%) in drinking water for 14 days. After a period of 14 days of L-thyroxine treatment we observed a significant increase of myostatin expression both in mRNA and protein level. However, decreased expression of myostatin mRNA and protein were observed in hypothyroid rats. Furthermore, our studies demonstrated that the upregulation of myostatin gene expression might be responsible for the loss of body weight induced by altered thyroid hormone levels. We concluded that myostatin played a role in a metabolic process in muscle that was regulated by thyroid hormone.

• 한국발생생물학회지:발생과생식
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• 제16권4호
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• pp.235-251
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• 2012

The reproductive activity in male mammals is well known to be regulated by the hypothalamus-pituitary-gonad axis. The hypothalamic neurons secreting gonadotropin releasing hormone (GnRH) govern the reproductive neuroendocrine system by integrating all the exogenous information impinging on themselves. The GnRH synthesized and released from the hypothalamus arrives at the anterior pituitary through the portal vessels, provoking the production of the gonadotropins(follicle-stimulating hormone (FSH) and luteinizing hormone (LH)) at the same time. The gonadotropins affect the gonads to promote spermatogenesis and to secret testosterone. Testosterone acts on the GnRH neurons by a feedback loop through the circulatory system, resulting in the balance of all the hormones by regulating reproductive activities. These hormones exert their effects by acting on their own receptors, which are included in the signal transduction pathways as well. Unexpected aberrants are arised during this course of action of each hormone. This review summarizes these abnormal phenomena, including various mutations of molecules and their actions related to the reproductive function.

• 한국발생생물학회지:발생과생식
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• 제22권2호
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• pp.119-132
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• 2018

GnRH (gonadotropin-releasing hormone) is a supreme hormone regulating reproductive activity in most animals. The sequences of amino acid and nucleic acid of GnRH reported up to now are examined from the evolutionary framework of Chordata. All identified GnRH are classified into GnRH1, GnRH2, or GnRH3. In all three forms of GnRH both N-terminal and C-terminal are conserved, which allows for effective binding to their receptors. The three amino acids in the middle of GnRH1 sequence have altered diversely from the primitive Chordata, which is indicative of the adaptation process to the ambient environment. GnRH2 and GnRH3 sequences are well conserved. There are more diverse modifications in the nucleic acids than in amino acid sequence of GnRH1. These variations can result from meiosis, mutation, or epigenetics and indicate that GnRH is the product of natural selection.

• 한국발생생물학회지:발생과생식
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• 제23권3호
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• pp.263-275
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• 2019

Based on our preliminary results, we examined the possible role of low-dose and chronic-exposing of the chemicals those are known as endocrine disrupting chemical (EDC), on the proliferation of uterine endometrium and the localization of steroid receptors. Immunohistochemical or immunofluorochemical methodology were employed to evaluate the localization of antigen identified by monoclonal antibody Ki 67 protein (MKI67), estrogen receptor 1 (ESR1), estrogen receptor 2 (ESR2), and progesterone receptor (PGR). In $133{\mu}g/L$ and $1,330{\mu}g/L$ di(2-ethylhexyl) phthalate (DEHP) and $50{\mu}g/L$ nonylphenol (NP) groups, the ratio of MKI67 positive stromal cells was significantly increased but not in $500{\mu}g/L$ NP group. The ratios of MKI67 positive glandular and luminal epithelial cells were also changed by the chronic administration of NP and DEHP in tissue with dose specific manner. ESR1 signals were localized in nucleus in glandular and luminal epithelia of control group but its localization was mainly in cytoplasm in DEHP and NP administered groups. On the other hand, it was decreased at nucleus of stromal cells in $1,330{\mu}g/L$ DEHP group. The colocalization patterns of these nuclear receptors were also modified by the administration of these chemicals. Such a tissue specific and dose specific localization of ESR2 and PGR were detected as ESR1 in all the uterine endometrial tissues. These results show that the chronic lows-dose exposing of NP or DEHP modify the localization and colocalization of ESRs and PGR, and of the proliferation patterns of the endometrial tissues.

• 생명과학회지
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• 제22권5호
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• pp.687-691
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• 2012

본 연구는 성숙마우스의 난소에서 황체형성호르몬수용체(luteinizing hormone receptor, LHR)와 beta-galctoside-binding animal lectin인 galetin-3 (Gal-3)의 발현분포를 면역조직화학방법으로 평가하였다. LHR은 활동(성숙) 황체에서 강하게 발현되는 반면에, Gal-3의 발현은 퇴행중인 황체와 폐쇄난포에서 높게 나타났다. 또한, 임신중인 마우스의 황체에서는 LHR의 면역반응이 강하게 나타났으나, Gal-3의 면역반응은 현저히 낮았다. 위의 결과를 종합해 볼 때, 성숙마우스의 난소에서 LHR과 Gal-3는 난소의 특정한 시기에 따라 다른 분포양상을 나타냄을 알 수 있었으며, 이들 각각의 단백질의 발현으로 보아 황체의 형성과 퇴행에서 상반된 역할을 할 것으로 여겨진다.

• Reproductive and Developmental Biology
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• 제33권4호
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• pp.229-236
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• 2009

The glycoprotein hormone family represents a class of heterodimers, that includes the placental hormone equine chorionic gonadotropin (eCG) and the anterior pituitary hormones- follitropin (FSH), lutropin (LH), and thyrotropin (TSH). The 4 hormones are heterodimers, with a common $\alpha$-subunit and unique $\beta$-subunits. eCG is the most heavily glycosylated of the known pituitary and placental glycoprotein hormones. Recent observations using single chain glycoprotein hormone analogs in which, the $\beta$-and $\alpha$-subunits are linked, implied that heterodimeric-like quaternary configuration is not a prerequisite for receptor/signal transduction. To study the function and signal transduction of tethered rec-eCG, a single chain eCG molecule was constructed and rec-eCG protein was produced. Molecular mass of the single chain is about 45 kDa. All mice were ovulated by tethered rec-eCG treatment. The dual activity of tethered rec-eCG was determined in receptor cell lines of nonequid species; in fact, this dual activity was proven in species other than horse. Tethered rec-eCG in equids does not bind to FSH receptors, suggesting that eCG is primarily an LH-like hormone in the horse. Taken together, these data suggest that tethered rec-eCG has dual activity in nonequid species in vitro. However, it has only LH-like activity in equid species in vitro.

• 한국발생생물학회지:발생과생식
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• 제25권4호
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• pp.225-234
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• 2021

The present study aimed to investigate the mechanism of cell surface receptor loss by two constitutively activating mutants (designated L469R, and D590Y) and two inactivating mutants (D417N and Y558F) of the luteinizing hormone receptor (LHR) in the Japanese eel Anguilla japonica, known to naturally occur in human LHR transmembrane domains. We investigated cell surface receptor loss using an enzyme-linked immunosorbent assay in HEK 293 cells. The expression level of wild-type eel LHR was considered to be 100%, and the expression levels of L469R and D417N were 97% and 101%, respectively, whereas the expression levels of D590Y and Y558F slightly increased to approximately 110% and 106%, respectively. The constitutively activating mutants L469R and D590Y exhibited a decrease in cell surface loss in a manner similar to that of wild-type eel LHR. The rates of loss of cell surface agonist-receptor complexes were observed to be very rapid (2.6-6.2 min) in both the wild-type eel LHR and activating mutants. However, cell surface receptor loss in the cells expressing inactivating mutants D417N and Y558F was slightly observed in the cells expressing inactivating mutants D417N and Y558F, despite treatment with a high concentration of agonist. These results provide important information on LHR function in fish and the regulation of mutations of highly conserved amino acids in glycoprotein hormone receptors.