Gene Expression Endpoints Following Subchronic Thiamethoxam Exposure in Adult Male Rabbits

Aim: to investigate the sub chronic toxicity of thiamethoxam on some parameters of reproductive performance in adult male rabbits including gene expression of LDH-C4, FSH? and LH? and GnRHR. Method: sixteen adult male Chinchilla rabbits were divided into two equal groups. Animals in the first group were treated orally with TMX at dose of 250 mg/kg body weight for 90 days. The second group was served as control. Result: Obtained results showed that TMX increased the relative weight of some reproductive organs including testis and prostate. Hormonal analysis revealed that, TMX induced a significant elevation in the serum testosterone level, while the concentrations of FSH and LH hormones did not exhibit any alterations between treated and control groups. In addition, LDH-C4, FSH? and LH? and GnRHR genes were down regulated in TMX treated group. Conclusion: Administration of thiamethoxam for 90 days in male rabbits induced a noticeable adverse effect on serum testosterone level and down regulated genes related to male rabbit reproductive performance

Genetic Variations of GNRH1, GNRHR and GPR54 Genes in Korean Girls with Central Precocious Puberty / 대한소아내분비학회지

PURPOSE: Central precocious puberty (CPP) is defined as any sign of secondary sexual maturation appears at an age lower than two standard deviations of the mean for the average age. This process is driven by activation of hypothalamic gonadotropin releasing hormone (GnRH) secretion. Many genes expressed in the hypothalamus have been identified to play an important role in the onset and the progression of puberty. In this study, the GNRH1, its receptor (GNRHR), and kisspeptin receptor (GPR54) genes were scanned to investigate sequence alterations and their distribution in Korean girls with CPP. METHODS: One hundred and one Korean girls with CPP were recruited as the case group and 51 normal Korean women as the control group. The DNAs were extracted and amplified by polymerase chain reaction (PCR), and the products were sequenced directly. Statistical analyses were performed, and P values of C in GNRH1, and c.1091T > A in GPR54. However, the other two (c.196C > T in GNRH1 and c.546T > C in GNRHR) were novel. There was no polymorphism that was significantly associated with early onset or rapid progression of puberty. CONCLUSION: Although the size of our study population was relatively small, simple genetic variations in GNRH1, GNRHR, and GPR54 genes are not likely to be a substantial factor directly associated with the onset and progression of puberty.

Genetic Variations of GNRH1, GNRHR and GPR54 Genes in Korean Girls with Central Precocious Puberty / 대한소아내분비학회지

PURPOSE: Central precocious puberty (CPP) is defined as any sign of secondary sexual maturation appears at an age lower than two standard deviations of the mean for the average age. This process is driven by activation of hypothalamic gonadotropin releasing hormone (GnRH) secretion. Many genes expressed in the hypothalamus have been identified to play an important role in the onset and the progression of puberty. In this study, the GNRH1, its receptor (GNRHR), and kisspeptin receptor (GPR54) genes were scanned to investigate sequence alterations and their distribution in Korean girls with CPP. METHODS: One hundred and one Korean girls with CPP were recruited as the case group and 51 normal Korean women as the control group. The DNAs were extracted and amplified by polymerase chain reaction (PCR), and the products were sequenced directly. Statistical analyses were performed, and P values of C in GNRH1, and c.1091T > A in GPR54. However, the other two (c.196C > T in GNRH1 and c.546T > C in GNRHR) were novel. There was no polymorphism that was significantly associated with early onset or rapid progression of puberty. CONCLUSION: Although the size of our study population was relatively small, simple genetic variations in GNRH1, GNRHR, and GPR54 genes are not likely to be a substantial factor directly associated with the onset and progression of puberty.

Effect of illumination stress on the expression of GnRH receptor in stomach of SD rat / 解剖学报

Objective To study the expression of gonadotropin releasing hormone receptor (GnRH receptor) in the stomach of Sprague-Dawley rat exposed to light stress. Methods We established illumination stressed models that the rats were exposed to continuous light(totally 64 rats, 32 rats for experiment and control group, respectively). Then,stomachs were taken from the rats when the rats exposed to continuous light for 1 day, 2 days, 3 days, 4 days, 1 week, 2 weeks, 3 weeks, 4 weeks and their control groups, respectively.The localization and the expression of GnRHR and GnRHR mRNA in stomachs mucous membrane were detected using immunohistochemistry, Western blotting and real-time PCR. Results Immunoreactivity was displayed mostly in the parietal cells in gastric gland. There were not differences of this distribution in all groups of constant illumination and their control. The immunoreactive materials were distributed on membrane and in cytoplasm of all positive cells, but not in nuclei. The level of GnRHR in rats exposed to continuous illumination were higher from one week to four weeks compared with that in control(P<0.05), and the level of GnRHR reached the peak when rats were exposed to constant illumination for two weeks (P<0.01). The quantity of GnRH mRNA in rats exposed to continuous illumination were higher from three weeks to four weeks compared with that in control(P<0.05). Conclusion The expression of GnRHR in digestive tract was effected by illumination stress.GnRH might regulate digestive function by interaction with GnRHR, suggesting that GnRH may be acted as a hormone, not only responded to normal physiological function of digestive tract but also responded to stress activity.

Molecular Genetic Analysis and Endocriological Evaluation of Isolated Hypogonadotropic Hypogonadism Presented with Delayed Puberty / 대한소아내분비학회지

PURPOSE: Isolated hypogonadotropic hypogonadism (HH) is a disorder of the hypothalamic-pituitary axis causing gonadotrophin releasing hormone or gonadotrophin deficiency. Kallman syndrome has a constellation of features, characterized by HH, hyposomia, deafness and congenital heart defects, whereas a normal sense of smell indicates idiopathic HH. Defects in some genes such as KAL-1, FGFR1, GNRHR and GPR54, have been described. The study was undertaken to identify the molecular defects of aforementioned genes and to evaluate clinical profiles in patients with HH. METHODS: Among the patients who visited the hospital due to delayed puberty from March 1995 to March 2006, seven male patients were suspected of having HH and included in this study. Clinical characteristics at diagnosis and endocrinological data including gonadotropin-releasing hormone (GnRH) agonist stimulation test were investigated. For molecular genetic evaluation, routine karyotyping in all patients and mutation analyses of the KAL, FGFR-1, GNRHR and GPR54 genes in six patients were performed. RESULTS: The study included 7 patients diagnosed as HH by GnRH stimulation; 4 with Kallman syndrome and 3 with idiopathic HH. No mutation was identified by DNA sequence analysis of KAL-1, FGFR1, GNRHR and GPR54 genes in 7 patients with HH. At diagnosis, chronologic age was 16.88+/-.90 years; height SDS, -0.36+/-.43; mean volume of the testis, 1.79+/-.76 mL. Of the patients with Kallman syndrome, 3 had sensory neural hearing loss, 2 congenital heart disease and 1 bilateral cryptorchidism. The olfactory bulb or sulci hypoplasia was found in all Kallman syndrome patients on the brain MRI. No abnormal finding was found in the brain MRI of the patients with idiopathic HH. Peak LH and FSH levels were 1.27+/-.60 IU/L and 1.15+/-.65 IU/L after GnRH stimulation. Baseline total testosterone level was 0.41+/-.24 ng/mL. The patients were treated with testosterone enanthate every 3-4 weeks for the mean duration of 40.60+/-8.61 months. During the follow-up period, 5 patients reached the final adult height with the mean height of 175.00+/-.47 cm (0.28+/-.14 SDS). CONCLUSION: For differential diagnosis of delayed puberty, physical, radiological, hormonal evaluations are all necessary. Many genes associated with Isolated HH were founded until now. But, mutations in these genes account for small proportion of Isolated HH yet. Further study of genes that regulate secondary sexual development and function will give important information regarding the development of normal puberty in humans.

A Familial Case of Idiopathic Hypogonadotropic Hypogonadism Occurred in a Boy and His Sister / 대한소아내분비학회지

Isolated gonadotropin deficiency can be idiopathic or a part of X-linked Kallmann syndrome associated with anosmia. There have been several trials to reveal the genetic mutations that affect gonadotropin secretion, and approximately 10% of sporadic patients have mutations in either gonadotropin releasing hormone receptor (GnRHR) or KAL1 gene. Here we report one familial cases of idiopathic hypogonadotropic hypogonadism occurred in a boy and his elder sister. They presented with delayed puberty and hypoplastic gonads, but normal sense of smell. We performed GnRHR and KAL1 mutation analysis, but could not find any mutation.

STUDIES ON DISTRIBUTION OF FSH, LH AND COLOCALIZATION WITH GnRHR IN RAT SUBMAXILARY GRANDS / 解剖学报

Objective To investigate the distribution of folliclestimulating hormone (FSH),luteinizing hormone (LH) and colocalization with gonadotropin releasing hormone receptor (GnRHR) in rat submaxilary glands. Methods Distribution of FSH, LH and colocalization with GnRHR consecutive sections of rat submaxilary glands were investigated by immunohistochemical colocalization methods. Results FSH and LH immunoreactivity were observed in the epithelial cells of serous acinus, secretory tubes, excretory ducts and granular convoluted tubule. The immunoreactive materials were brown and distributed in the cytoplasma with negative nucleolus. The results of immunohistochemical colocalization showed not only FSH but also GnRHR immunoreactivity in the same structure of two adjacent section. The distribution of the positive substance of FSH and GnRHR were similar to each other. The most of showing GnRHR immunoreactivity cells were detected LH immunoreactivity in the same structure of two adjacene section and the others were immunonegative. The GnRNR immunoreactive materials were distributed in the cytoplasma with negative nucleolus.Conclusion The epithelial cell of serous acinus, secretory tubes, excretory ducts and granular convoluted tubule of rat submaxilary glands may be synthesized and secreted FSH and LH. These cells with FSH and LH positive immunoreaction of rat submaxilary glands may be regulated by Gonadotropin releasing hormone (GnRH) through autocrine or paracrine.;

Expression of GnRH and GnRH-R in various endometrial tissue and its significance / 解放军医学杂志

Objective To detect the protein expression of gonadotropin-releasing hormone (GnRH) and its receptor (GnRH-R) in various endometrial tissues, and to investigate its significance. Methods Immunohistochemistry was employed to analyse the protein expression and localization of GnRH and GnRH-R from endometriosis(EMS), endometrial hyperplasia, endometrial carcinoma and control group. Results GnRH and GnRH-R are expressed at the protein level in all eutopic endometrium, in 50% ectopic endometrium and 92.3% endometrial hyperplasia, while the expressional rate in endometrial carcinoma are 58.8% and 82.4%, respectively. The majority of GnRH and GnRH-R existed in the plasma of glandular epithelium cells and some stroma cells. Conclusions There exists GnRH and its receptor proteins in endometrial tissues, and their abundant expression in endometriosis, endometrial hyperplasia and in endometrial carcinoma may imply that they could be used in clinical diagnosis and treatment.