• 생명과학회지
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• 제15권1호
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• pp.112-117
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• 2005

하천변에 사는 식물들은 침수 저항성을 갖추고 있는데 그중 Ranunculus속이나 Rumex속에 속하는 일부 반수생 식물들에서 볼 수 있는 것처럼, 엽병이 급격한 생장을 일으켜 잎이 수표면에 이르게 함으로써 호흡할 수 있는 조건을 확보하는 현상은 식물체내에 축적된 에틸렌에 의하여 매개되는 현상이다. 침수 조건에서는 식물 조직 내에 에틸렌이 축적되며, 축적된 에틸렌은 옥신 등 다른 식물호르몬에 대한 조직의 감수성을 증가시켜 생장을 촉진한다. 증가된 생장으로 잎이 수표면에 이르게 되면 다시 공기를 접촉하여 호흡할 수 있게 되고, 식물체내에 축적되었던 에틸렌은 대기 중으로 확산하여 나가게 되므로 체내 에틸렌 농도가 감소하여 생장률이 침수 이전 수준으로 되돌아간다. 에틸렌에 의한 옥신의 감수성 증가는 선량 반응 곡선에 비추어 수용체의 친화도 증가가 수반되는 것으로 생각되는데, 아직 옥신 수용체가 밝혀지지 않아 분자생물학적 기작은 연구되어야 할 과제로 남아있다. 최근 옥신 수용체 발견의 가능성이 높아지고 있으며, 따라서 에틸렌에 의한 옥신 수용체의 옥신에 대한 감수성 조절기작을 탐구할 수 있는 길이 열릴 것으로 기대된다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권22호
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• pp.9739-9745
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• 2014

Purpose: We aimed to evaluate the effects of hormone receptor, HER2, and epidermal growth factor receptor (EGFR) expression on epithelial ovarian cancer (EOC) prognosis and investigate whether or not phenotypic subtypes might exist. Materials and Methods: The medical records of 82 patients who were diagnosed with EOC between 2003 and 2012 and treated by platinum-based chemotherapy were retrospectively evaluated. Expression of EGFR, oestrogen (ER), progesterone (PR), and cerbB2 (HER2) receptors were assessed immunohistochemically on paraffin-embedded tissues of these patients. Three phenotypic subtypes were defined according to ER, PR, and HER2 expression and associations of these with EGFR expression, clinicopathologic features, platinum sensitivity, and survival were investigated. Results: When we classified EOC patients into three subtypes, 63.4% had hormone receptor positive (HR(+)) (considering breast cancer subtypes, luminal A), 18.3% had triple negative, and 18.3% had HER2(+) disease. EGFR positivity was observed in 37 patients (45.1%) and was significantly more frequent with advanced disease (p=0.013). However, no significant association with other clinicopathologic features and platinum sensitivity was observed. HER2(+) patients had significantly poorer outcomes than HER2(-) counterparts (triple negative and HR positive patients) (p=0.019). Multivariate analysis demonstrated that the strongest risk factor for death was residual disease after primary surgery. Conclusions: Triple negative EOC may not be an aggressive phenotype as in breast cancer. The HER2 positive EOC has more aggressive behaviour compared to triple negative and HR(+) phenotypes. EGFR expression is more frequent in advanced tumours, but is not related with poorer outcome. Additional ovarian cancer molecular subtyping using gene expression analysis may provide more reliable data.

• Clinical and Experimental Reproductive Medicine
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• 제23권3호
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• pp.269-275
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• 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.

• 생명과학회지
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• 제28권2호
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• pp.265-273
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• 2018

에스트로겐(E2)은 유방암의 발달과 진행에 관여하며, 에스트로겐 수용체(ER)에 의해 매개된다. ER은 유방암세포에서 epidermal growth factor receptor와 insulin-like growth factor-1 receptor의 신호전달경로들 사이에서 다양한 cross-talk을 통하여 세포의 증식, 이주, 침습 및 약물에 대한 저항성을 일으키는데 중요한 역할을 수행한다. 유방암은 내분비신호전달의 항상성 붕괴에 의해 주로 발생되며, 특히 E2/IGF-1/EGF와 ER/G-protein estrogen receptor (GPER)/IGF-1R/EGFR, 그리고 이들의 세포내 신호전달 매개인자들의 통제되지 않는 발현과 활성증가에 의해 유발된다. 이러한 변화는 E2와 성장인자 신호전달 사이의 복잡한 cross-talk에 영향을 주어 결국 암의 진행과 내분비조절인자들에 대한 저항성을 갖게 된다. 따라서, E2와 성장인자들 사이의 cross-talk에 관한 분자적 기전을 단계별로 규명하는 것은 유방암의 다양한 유형에 따른 맞춤형 치료에 기여할 것으로 사료된다. 특히, 다양한 유전형 및 표현형을 가진 유방암의 치료를 위한 전략으로서, ER+ 호르몬의존성 유방암세포에 대한 aromatase 억제제 및 E2작용 차단제의 사용과 E2와 성장인자들 사이의 cross-talk에 의한 암세포의 증식억제를 위한 IGF-1R/EGFR 활성차단제의 사용 등을 들 수 있다. 뿐만 아니라, ER과 EGFR/IGF-1R 사이의 cross-talk에 의해 조절되는 ECM 분자들의 발현변화는 유방암세포의 전이에 대한 표적치료제를 위해 활용될 수 있다. 따라서, 암의 진행과 관련된 ER, GPER, IGF-1R 및 EGFR 매개에 의한 신호전달경로들 사이의 cross-talk에 관한 보다 더 자세한 분자적 수준의 규명이 필요할 것으로 사료된다.

• 한국응용곤충학회지
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• 제61권1호
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• pp.85-90
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• 2022

인슐린(insulin)과 insulin-like growth factor-1 (IGF-1)은 척추동물에서 대사, 생장, 수명 등의 여러 생리대사를 조절하는 중요한 호르몬이다. 곤충에서도 IGF-1과 구조적으로 유사한 insulin-like peptide (ILP)들이 존재하며 이들이 곤충 생리 조절에 중요하게 관여함이 밝혀졌다. 이번 총설에서 곤충 ILP 및 초파리(Drosophila melanogaster) 유전체 분석을 통해 척추동물에 존재하는 인슐린 및 IGF-1 수용체 신호전달계와 유사하다고 확인된 ILP 수용체 신호전달계에 대해 설명하고자 한다. 추가적으로, 곤충 체내의 영양 상태에 따라 조절되는 뇌에서의 ILP의 합성과 분비, ILP에 의한 대사의 생리적 조절에 대해 논한다. 또한 ILP가 생장, 발달, 생식, 휴면에 기여하는 바도 논의하고, 마지막으로 ILP 수용체 신호전달계 제어를 통한 해충 방제에의 이용 가능성에 대해 제안하고자 한다.

• Asian-Australasian Journal of Animal Sciences
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• 제27권1호
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• pp.147-154
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• 2014

This review focuses on modulation of growth hormone (GH) and its downstream actions on periparturient dairy cows undergoing physiological and metabolic adaptations. During the periparturient period, cows experience a negative energy balance implicating that the feed intake does not meet the total energy demand for the onset of lactation. To regulate this metabolic condition, key hormones of somatotropic axis such as GH, IGF-I and insulin must coordinate adaptations required for the preservation of metabolic homeostasis. The hepatic GHR1A transcript and GHR protein are reduced at parturition, but recovers on postpartum. However, plasma IGF-I concentration remains low even though hepatic abundance of the GHR and IGF-I mRNA return to pre-calving value. This might be caused by alternation in IGFBPs and ALS genes, which consequently affect the plasma IGF-I stability. Plasma insulin level declines in a parallel manner with the decrease in plasma IGF-I after parturition. Increased GH stimulates the lipolytic effects and hepatic glucose synthesis to meet the energy requirement for mammary lactose synthesis, suggesting that GH antagonizes insulin-dependent glucose uptake and attenuates insulin action to decrease gluconeogenesis.

• Animal Bioscience
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• 제35권3호
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• pp.399-409
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• 2022

Objective: Follicle-stimulating hormone (FSH) is the central hormone involved in mammalian reproduction, maturation at puberty, and gamete production that mediates its function by control of follicle growth and function. The present study investigated the mutations involved in the regulation of FSH receptor (FSHR) activation. Methods: We analyzed seven naturally-occurring mutations that were previously reported in human FSHR (hFSHR), in the context of equine FSHR (eFSHR); these include one constitutively activation variant, one allelic variant, and five inactivating variants. These mutations were introduced into wild-type eFSHR (eFSHR-wt) sequence to generate mutants that were designated as eFSHR-D566G, -A306T, -A189V, -N191I, -R572C, -A574V, and -R633H. Mutants were transfected into PathHunter EA-parental CHO-K1 cells expressing β-arrestin. The biological function of mutants was analyzed by quantitating cAMP accumulation in cells incubated with increasing concentrations of FSH. Results: Cells expressing eFSHR-D566G exhibited an 8.6-fold increase in basal cAMP response, as compared to that in eFSHR-wt. The allelic variation mutant eFSHR-A306T was not found to affect the basal cAMP response or half maximal effective concentration (EC₅₀) levels. On the other hand, eFSHR-D566G and eFSHR-A306T displayed a 1.5- and 1.4-fold increase in the maximal response, respectively. Signal transduction was found to be completely impaired in case of the inactivating mutants eFSHR-A189V, -R572C, and -A574V. When compared with eFSHR-wt, eFSHR-N191I displayed a 5.4-fold decrease in the EC₅₀ levels (3,910 ng/mL) and a 2.3-fold decrease in the maximal response. In contrast, cells expressing eFSHR-R633H displayed in a similar manner to that of the cells expressing the eFSHR-wt on signal transduction and maximal response. Conclusion: The activating mutant eFSHR-D566G greatly enhanced the signal transduction in response to FSH, in the absence of agonist treatment. We suggest that the state of activation of the eFSHR can modulate its basal cAMP accumulation.

• Animal Bioscience
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• 제35권7호
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• pp.989-998
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• 2022

Objective: This study investigated the effects of intrauterine growth restriction (IUGR) during late pregnancy on the cell growth, proliferation, and differentiation in ovine fetal thymuses. Methods: Eighteen time-mated Mongolian ewes with singleton fetuses were allocated to three groups at d 90 of pregnancy: restricted group 1 (RG1, 0.18 MJ ME/body weight [BW]^0.75/d, n = 6), restricted group 2 (RG2, 0.33 MJ ME/BW^0.75/d, n = 6) and control group (CG, ad libitum, 0.67 MJ ME/BW^0.75/d, n = 6). Fetuses were recovered at slaughter on d 140. Results: The G0/G1 phase cell number in fetal thymus of the RG1 group was increased but the proliferation index and the expression of proliferating cell nuclear antigen (PCNA) were reduced compared with the CG group (p<0.05). Fetuses in the RG1 group exhibited decreased growth hormone receptor (GHR), insulin-like growth factor 2 receptor (IGF-2R), and their mRNA expressions (p<0.05). For the RG2 fetuses, there were no differences in the proliferation index and PCNA expression (p>0.05), but growth hormone (GH) and the mRNA expression of GHR were lower than those of the CG group (p<0.05). The thymic mRNA expressions of cyclin-dependent protein kinases (CDKs including CDK1, CDK2, and CDK4), CCNE, E2-factors (E2F1, E2F2, and E2F5) were reduced in the RG1 and RG2 groups (p<0.05), and decreased mRNA expressions of E2F4, CCNA, CCNB, and CCND were occurred in the RG1 fetuses (p<0.05). The decreased E-cadherin (E-cad) as a marker for epithelial-mesenchymal transition (EMT) was found in the RG1 and RG2 groups (p<0.05), but the OB-cadherin which is a marker for activated fibroblasts was increased in fetal thymus of the RG1 group (p<0.05). Conclusion: These results indicate that weakened GH/IGF signaling system repressed the cell cycle progression in G0/G1 phase in IUGR fetal thymus, but the switch from reduced E-cad to increased OB-cadherin suggests that transdifferentiation process of EMT associated with fibrogenesis was strengthened. The impaired cell growth, retarded proliferation and modified differentiation were responsible for impaired maturation of IUGR fetal thymus.

• Asian-Australasian Journal of Animal Sciences
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• 제21권12호
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• pp.1760-1765
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• 2008

A total of 60 one-day-old Yellow-feather broiler chickens were allotted into treatment and control groups. The treatment group was fed with the diet supplemented with 3% conjugated linoleic acid (CLA) for 48 d, while control group was fed with the diet supplemented with 3% rapeseed oil. Chickens were slaughtered in each group at the age of 49 d, and the blood and the abdominal adipose tissue were sampled. Serum cLeptin and serum cAdiponectin were measured by ELISA. The total RNA was extracted from adipose tissue to measure the abundance of the chicken growth hormone receptor (cGHR), insulin-like growth factor 1 (cIGF-1), insulin-like growth factor I receptor (cIGF-IR), peroxisome proliferator-activated receptor gamma ($cPPAR{\gamma}$), cAdiponectin and cAdipoIR mRNA by RT-PCR using ${\beta}$-actin as an internal standard. Results showed that the CLA decreased the abdominal fat index by 20.93% (p<0.05). The level of serum cLeptin but not serum cAdiponectin was significantly increased by CLA treatment (p<0.05). CLA down-regulated the relative abundance of cGH-R mRNA and $cPPAR{\gamma}$ mRNA in abdominal adipose tissue by 24.74% (p<0.05) and 66.52% (p<0.01) respectively. However, no differences were found between CLA treatment group and control group (p>0.05) in the relative abundance of cIGF-1, cIGF-IR, cAdiponectin, and cAdipoIR mRNA in abdominal adipose tissue. The data suggested that CLA inhibited abdominal fat deposition in broiler chicken may be determined by decreasing the GHR available for GH, and by inhibiting the differentiation of preadipocytes via down-regulation of $PPAR{\gamma}$, but independent of IGF and (or) GH-IGF pathway or adiponectin action.

• Journal of Animal Science and Technology
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• 제45권1호
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• pp.13-22
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• 2003

성장호르몬 유전자는 하나의 작은 공통 선조 유전자로부터 아주 오랜 기간동안 유전자 중복에 의해 진화되어 온 그룹들 중의 하나이다. 이들에 속하는 유전자들은 동물 종간에 구조적인 상동성과 기능적 공통성 등 유사성이 비교적 높게 나타난다. 이런 연구결과들을 근거로 하여 소 성장호르몬 유전자에서 아미노산을 암호화하는 영역으로부터 새로운 아미노산의 변이(missense mutation)를 검출하였고, 이 변이의 대립유전자 빈도는 소(cattle)의 종(species) 및 품종의 지리적 분포에 따라 일정한 경향 치를 보여 주었다. 한편 변경되어진 아미노산은 Tryptophan으로 이는 생물체에 존재하는 많은 단백질들을 구성하는 아미노산중에서도 그 출현빈도가 가장 낮은 것이다. 또한 검출된 변이는 성장호르몬이 그의 수용체와 강하게 결합하는 부위로서, 성장호르몬의 구조적 변이를 초래하여 수용체와의 결합이 비정상적으로 이루어져, 이후 성장호르몬이 표적세포로의 신호전달과 같은 역할을 제대로 수행치 못하게 되고, 이로 인하여 가축의 표현되어지는 경제형질에 영향을 미칠 것으로 추정된다. 그러므로 이러한 대립유전자를 보유하는 개체는 집단에서 제거하는 방법에 의한 개량이 가능할 것으로 사료된다.