The influence of chronic intermittent hypoxia on hypothalamic-somatotropic axis in rats / 中华内科杂志

Objective To investigate the effects of chronic intermittent hypoxia on somatotropic axis hormone levels in rats.Methods Mature male Wistar rats were exposed to air or intermittent hypoxia randomly.The serum levels of growth hormone-releasing hormone (GHRH),growth hormone (GH) and somatostatin (SS) were measured before exposure,at the 4th,8th,and 12th week after exposure.Different hormone levels in two groups were compared and analyzed.Results Compared with the control group,GHRH levels in chronic intermittent hypoxic group showed a significant decline at the 4th week [(732.77± 46.99)pg/ml vs.(893.59±40.00) pg/ml,P＜0.05],while SS levels at the 8th week [(30.71 ±2.27) pg/ml vs.(44.69±3.36) pg/ml,P＜0.05] and GH levels at the 12th week [(1.20±0.29) ng/ml vs.(2.06±0.13) ng/ml,P＜0.05]were similarly reduced.As the duration of intermittent hypoxia was prolonged,the GHRH levels did not decrease further [4th week (732.77±46.99) pg/ml vs.8th week (607.54± 131.61) pg/ml vs.12th week (730.05±40.63) pg/ml,P＞0.05].However,the serum SS levels decreased further from the 8th week to the 12th week [(30.71±2.27) pg/ml vs.(24.41±4.06) pg/ml,P＜0.05].Conclusion Chronic intermittent hypoxia might inhibit the function of somatotropic axis.Hypothalamic hormones are the earlyonesto be influenced,thereafter the entire axis.

The treatment effect of novel hGHRH homodimer to male infertility hamster

Extra-hypothalamic growth hormone-releasing hormone (GHRH) plays an important role in reproduction. To study the treatment effect of Grin (a novel hGHRH homodimer), the infertility models of 85 male Chinese hamsters were established by intraperitoneally injecting 20 mg/kg of cyclophosphamide once in a week for 5 weeks and the treatment with Grin or human menopausal gonadotropin (hMG) as positive control was evaluated by performing a 3-week mating experiment. 2–8 mg/kg of Grin and 200 U/kg of hMG showed similar effect and different pathological characteristics. Compared to the single cyclophosphamide group (0%), the pregnancy rates (H-, M-, L-Grin 26.7, 30.8, 31.3%, and hMG 31.3%) showed significant difference, but there was no difference between the hMG and Grin groups. The single cyclophosphamide group presented loose tubules with pathologic vacuoles and significant TUNEL positive cells. Grin induced less weight of body or testis, compactly aligned tubules with little intra-lumens, whereas hMG caused more weight of body or testis, enlarging tubules with annular clearance. Grin presented a dose-dependent manner or cell differentiation-dependentincrease in testicular GHRH receptor, and did not impact the levels of blood and testicular GH, testosterone. Grin promotes fertility by proliferating and differentiating primitive cells through up-regulating testicular GHRH receptor without triggering GH secretion, which might solve the etiology of oligoasthenozoospermia.

1-methylhydantoin inhibits secretion of growth hormone in rabbits / 中国药理学通报

Aim Toexplorewhether1-methylhydan-toin(MH)could inhibit the basal secretion of growth hormone (GH ) and suppress the promoting effect of growth hormone-releasing hormone (GHRH ) in rab-bits.Methods Thirty-sixrabbitswererandomlydi-vided into six experimental groups according to the kind of dosing drugs,namely normal saline group(A), MH group (B ),octreotide group (C ),GHRH group (D),GHRH +MH group(E),GHRH +octreotide group(F),with 6 rabbits in each group.Blood was sampled (1. 0 mL each time)from each rabbit before injecting drugs and 5,15,30,45,60 min after drug administration.Clotting spontaneously,rabbits blood samples were centrifugated for 20 minutes at approxi-mately 1000 ×g and the supernatant was collected. Serum GH concentrations were determined by enzyme linked immunosorbent assay kit(ELISA Kit).Mean-while,the behavior of rabbits in each group after injec-tingdrugswascloselyobserved.Results TheGH level of rabbits in group A at each time point had no significant differences(P>0. 05 ).Group B and group C rabbit GH levels were significantly lower than those of group A (P<0. 05 ),while GH levels in group D were obviously higher than those of group A (P <0. 05 ).Compared with group D,rabbit GH levels in group E and group F decreased markedly(P<0. 05 ). No obvious toxic and side effects had been observed within one week after the experimental rabbits were ad-ministered corresponding drugs by intravenous injec-tion.Conclusions 1-methylhydantoincouldinhibit the basal secretion of GH in rabbits.1-methylhydan-toin could suppress the promoting effect of GHRH in rabbits.

Effect of human growth hormone releasing hormone receptor splice variant type 1 on proliferation of human liver cancer HepG2 cells / 吉林大学学报(医学版)

Objective:To investigate the effect of human growth hormone releasing hormone receptor splice variant type 1 (GHRHR SV1) on the proliferation of human liver cancer HepG2 cells,and to clarify the proliferation effect of GHRHR SV1 on the human cancer cells.Methods:The GHRHR SV1 plasmids were transfected into the human HepG2 cells to construct the HepG2-SV1 cell line.HepG2 group(HepG2 cells),HepG2-empty group(HepG2-pcDNA3.0 cell line) and HepG2-SV1 group(HepG2-SV1 cells) were set up.PCR and Western blotting methods were used to identify the HepG2-SV1 cell line;CCK-8 method was used to detect prolifernation rate of cells;colony formation assay was used to detect the colony formation rate of cells;cell wound healing assay was used to evaluate the migration rate of cells.Results:The PCR and Western blotting results showed the HepG2-SV1 cell line expressed GHRHR SV1 steadily.The CCK-8 results showed that the proliferation rate of the HepG2-SV1 cells in HepG2-SV1 group was higher than that of the HepG2-pcDNA3.0 cells in HepG2-empty group(P<0.05).The colony formation assay results showed that the colony formation rate of HepG2-SV1 cells in HepG2-SV1 group was 3.5 times higher than that of the HepG2-pcDNA3.0 cells in HepG2-empty group(P<0.05).The cell wound scratch assay results showed that the migration rate of the HepG2-SV1 cells in HepG2-SV1 group was higher than that of the HepG2-pcDNA3.0 cells in HepG2-empty group(P<0.05).Conclusion:GHRHR SV1 could increase the proliferation of HepG2 cells.

A cross-sectional study of cryptorchidism in children: testicular volume and hormonal function at 18 years of age

Purpose To evaluate the relationship between unilateral or bilateral criptorchidism, patient age, primary location of the gonad and modality of treatment with testicular volume and hormonal status at 18 years in patients diagnosed and treated for cryptorchidism during childhood. Materials and Methods Testicular volume, LH, FSH, and testosterone were evaluated in 143 young men at 18 years treated in childhood for unilateral (n=103) or bilateral (n=40) cryptorchidism. Results Unilateral cryptorchidism: Location of testis was prescrotal in 36 patients, inguinal in 52 and non-palpable in 15. The mean volume was 9.7 mL compared to 16.2 mL. for the spontaneously descended testicle in unilateral cryptorchidism. However, 22 patients who received HCG had a significantly bigger testis (11.8 mL.) than those treated with primary surgery (9.2 mL). The results showed a significant positive correlation between testicular volume and patient age at treatment. Bilateral cryptorchidism Location of testis was prescrotal in 34 cases, inguinal in 40 and 6 patients with non-palpable testicles. Mean volume at 18 years was 12.9 mL, greater than unilateral cryptorchid testis (9.7 mL) but smaller than healthy contralateral in unilateral cases (16.2 mL). There were significant differences in the testicular growth for bilateral patients with testicular descent after being treated with HCG (14.4 mL) in respect with those untreated (11.1 mL) or those who underwent primary surgery (11.4 mL). There was a significant positive correlation between the testicular volume and palpable (12.4 mL) or non-palpable testis (10.4 mL). There was a correlation between unilateral or bilateral cryptorchidism and levels of FSH. Conclusions Testicular volume and hormonal function at 18 years for patients diagnosed and treated for cryptorchidism during childhood are strongly influenced by whether the undescended testis was unilateral or bilateral. Location of the testes at diagnosis or ...

Changes of plasma growth hormone releasing peptide level and its influencing factors in patients with hyperthyroidism / 中国基层医药

Objective To study the changes of plasma growth hormone releasing peptide(Ghrelin)level and its influencing factors in patients with hyperthyroidism.Methods 55 patients with hyperthyroidism (observation group)and 55 healthy persons (control group)were selected.ELISA was used to detect plasma indicators before and after treatment.The level of body fat percentage,Ghrelin,S -TSH and FT3 ,FT4 of the two groups before and after treatment were compared,and the relationship between Ghrelin and FT3 ,FT4 ,percentage of body fat,plasma S -TSH was analyzed.Results Compared with the control group,the percentage of body fat,Ghrelin and S -TSH level in the observation group were lower,and FT3 ,FT4 levels were higher,there were significant differences between the two groups(t1 =5.021,t2 =9.628,t3 =23.054,t4 =29.325,t5 =28.967,P <0.05).Compared with before treatment,the body fat percentage,Ghrelin and S -TSH level of the observation group were higher after treatment,and FT3 ,FT4 levels were lower after treatment,the differences were statistically significant(t6 =5.282,t7 =8.651,t8 =21.835,t9 =27.126,t10 =26.855,P <0.05).The correlation analysis showed that FT3 and FT4 were negatively correlated with plasma Ghrelin level(r =-0.44,-0.39,P <0.05),the percentage body fat and S -TSH had positive relationship with plasma Ghrelin level (r =0.31,0.33,P <0.05).Conclusion The plasma Ghrelin level in the patients with hyperthyroidism is lower than healthy subjects,and its level is related with FT3 ,FT4 ,percentage of body fat and S -TSH,the detection of the above indicators has important value for the assessment of hyperthyroidism.

The Clinical Significance of Ghrelin Level in Hp Related Upper Gastrointestinal Diseases / 天津医药

Objective To investigate the impact and clinical significance of helicobacter pylori (Hp) elimination on ghrelin. Methods Forty patients with chronic superficial gastritis (CSG), 42 patients with chronic atrophic gastritis (CAG), 41 patients with peptic ulcer (PU) and 17 patients with gastric adenocarcinoma (CA) were included in this study. All of pa-tients in four groups were Hp-positive. Forty patients with Hp-negative were used as control. The Hp elimination were only performed in CAG,CSG and PU groups. The serum ghrelin and pepsinogen (PG) levels before and after Hp elimination were detected with ELISA assay in CSG, CAG and PU groups. The correlation between PG and glrelin was also detected. The ex-pression of ghrelin in gastric mucosa was detected by RT-PCR. Results Comparing with control group (30.41 ± 8.97), the ghrelin level was increased in PU group (35.42±9.87), but which were decreased in CAG group (18.59±8.19) and CA group (18.33±6.88). There was no significant difference in ghrelin level between CSG group (26.08±9.14) and control group. After Hp elimination, the serum and gastric mucosa ghrelin levels were significantly increased in CSG group (P＜0.01), but both serum and gastric mucosa ghrelin levels were significantly decreased in PU group (P＜0.01). And no significant difference in the level of ghrelin after Hp elimination in CAG group (P>0.05). A positive correlation was found between serum PGⅠ/PGⅡand serum ghrelin level in CSG, CAG and CA groups (r=0.668,P＜0.01). Conclusion Hp elimination has an impact on ghrelin level in patients with upper gastrointestinal diseases. The changes of ghrelin level related to PGⅠ/PGⅡ. Ghrelin can be used as one of the indexes of diagnostic and prognostic evaluation in Hp related upper gastrointestinal diseases.

The changes of ghrelin, growth hormone, growth hormone releasing hormone and their clinical significances in patients with chronic obstructive pulmonary disease / 中华内科杂志

Objective To investigate the changes of plasma ghrelin,growth hormone (GH) and growth hormone releasing hormone (GHRH) and gastric ghrelin in patients with chronic obstructive pulmonary disease( COPD ) and to explore their clinical significances.Methods Plasma ghrelin,GH,GHRH,TNFα,IL-6 and C reactive protein (CRP) were measured in 40 COPD patients and 20 controls with chronic bronchitis. Correlated factors of plasma ghrelin,TNFα,IL-6,CRP were analyzed. Body composition was assessed with bioelectrical impedance analysis.The expression of gastric ghrelin in patients with COPD was detected.Results Plasma ghrelin was higher in the underweight patients than in the normal weight patients and in the controls [ ( 1.78 ± 0.46 ) ng/L,( 1.39 ± 0.46 ) ng/L,( 1.36 ± 0.39 ) ng/L,respectively].Plasma GH was lower in the underweight patients than in the normal weight patients and in the controls [(4.12 ±0.83) μg,/L,(5.17 ±0.72) μg/L,(6.49 ± 1.13) μg/L,respectively].Plasma GHRH was lower in the underweight patients than in the normal weight patients and in the controls [ (20.43 ± 4.41 ) ng/L,(23.47 ± 3.97) ng/L,( 27.48 ± 10.06) ng/L,respectively ].Plasma ghrelin was higher in the underweight patients than in the controls ( P ＜ 0.01 ).Plasma ghrelin was higher in the underweight patients than in the normal weight patients with COPD.Plasma ghrelin (log transformed) was negatively correlated with BMI and percentage of body fat in the COPD patients.Plasma GHRH was positively correlated with ghrelin in the underweight patients ( r =0.515,P ＜ 0.05 ),while no correlation was found between plasma G H and ghrelin in the underweight patients (r =0.415,P ＞ 0.05 ).Plasma ghrelin was positively correlated with TNFα and IL-6 in the underweight patients.The gastric expression of ghrelin showed no evident difference between the patients with COPD and the controls.Conclusions The plasma GH in COPD patients may not be correlated with ghrelin.The plasma ghrelin level may be a useful indicator for malnutrition in COPD patients.Plasma ghrelin might be involved in the pathogenesis of CODP by affecting the body energy metabolism.

Analysis on serum ghrelin levels and its correlation with metabolic disorders in elderly Chinese / 中华老年医学杂志

Objective To measure serum ghrelin level in elderly Chinese, and investigate the relationship of the serum ghrelin level with age, obesity and other metabolic disorders. Methods A total of 109 men aged over 60 years without history of smoking and alcohol consumption from health examination were enrolled in this study. Subjects were excluded if they had serious diabetic complications, coronary artery disease and hepatic or renal dysfunction. A cross sectional study was made on ghrelin level and the correlated metabolic disorders. Results Compared with ghrelin level in subjects with normal BMI [(823. 57±410.40) ng/L], the ghrelin level was significantly decreased in overweight and obese elderly male, [(442.42 ± 171.10) ng/L and (434.64 ± 177.65) ng/L respectively]. ghrelin was significantly lower in subjects with three or more metabolic disorders (420.84±165.91) ng/L than in those with less disorder. Single factor analysis showed ghrelin was inversely associated with BMI, TG and uric acid (r=-0.359,-0.243,-0.189), but it was not associated with age, blood pressure, fasting glucose and insulin levels. Multivariate analysis revealed only BMI significantly affected the level of ghrelin (β =-0.386). Conclusions BMI is closely associated with ghrelin in elderly male,ghrelin is significantly lower with increased number of metabolic disorders.

Study on the Reciprocal Interactions between Growth Hormone and Ghrelin in the Rat / 대한소아내분비학회지

PURPOSE: The aim of this study was to determine whether there is a feedback relationship between pituitary growth hormone (GH) and gastric ghrelin. METHODS: We intravenously administered 10 microgram of either rat ghrelin or normal saline to adult male Sprague-Dawley rats and then measured the plasma GH levels and the mRNA expression levels of pituitary GH mRNA and hypothalamic GH-releasing hormone (GHRH) mRNA. Human GH (500 microgram/kg, twice a day) or normal saline was subcutaneously administered to rats with or without food for 3 days. Thereafter, the plasma ghrelin levels and the ghrelin mRNA levels in the stomach were measured. RESULTS: The plasma GH levels increased more significantly in rats that were administered ghrelin than in controls (P<0.05). The mRNA levels of pituitary GH and hypothalamic GHRH were similar in the 2 groups. The plasma ghrelin levels and the stomach ghrelin mRNA levels were not affected by GH administration. Fasting significantly increased plasma ghrelin levels (P<0.05) and stomach ghrelin mRNA levels (P<0.05). CONCLUSION: Exogenous ghrelin administration only stimulated GH secretion without stimulating the synthesis of GH and GHRH. The synthesis and secretion of ghrelin were not suppressed by exogenous GH administration. These findings indicate that there is no feedback relationship between pituitary GH and gastric ghrelin.

Role of Glucocorticoids in Fasting-induced Changes in Hypothalamic and Pituitary Components of the Growth Hormone (GH)-axis

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 sham-operated controls. In sham- operated 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.

Response to the Combined Pituitary Stimulation Test by CRH, GHRH, GnRH and TRH in Normal Human According to Age and Gender / 대한내분비학회지

BACKGROUND: It has been already known that each trophic hormone in combined pituitary responsiveness according to gender and age brings about variable response, but in Korea, there has been no actual data. In this study, in order to assess the pituitary responsiveness, a combined pituitary stimulation test was performed in Korean subjects with the variation in CRH, GHRH, GnRH, and TRH according to their age and gender. Were these the variables that were changed according to age and gender? Clarify that. Also, it might be good to write out the abbreviations.) METHOD: Fourteen physically and mentally healthy male subjects and fourteen female subjects, also physically and mentally healthy, underwent the combined anterior pituitary stimulation test by CRH, GHRH, LHRH, and TRH. Each gender group was divided further into young(meanSE; male: 231, female: 221) and old (mean; male: 513, female: 522) groups. RESULTS: There were significant differences between the gender and age groups. The Peak GH level and maximal GH increment were significantly increased in young men compared to old men. The Peak ACTH level and maximal ACTH increment were significantly increased in old men as opposed to young men. The Peak PRL level, maximal PRL increment, Peak TSH level, and maximal TSH increment were significantly increased in old women compared to old men. The Peak FSH level was significantly increased in the two old groups compared to the young groups, which showedindependence in gender, and the maximal FSH increment was significantly increased in old men when compared with the young men. CONCLUSION: These results show that in order to for accurate interpretation of the response from the combined pituitary stimulation test, it is necessary to consider age and gender of the subjects. We suggest response values of the combined pituitary stimulation test in terms of age and gender in healthy Korean subjects.

The Role of Protein Kinase C and Its Effect on GHRH in the Regulation of Hormone Secretion by Somatotrophinomas / 华中科技大学学报（医学）（英德文版）

Phorbol ester-induced release of growth hormone (GH) and prolactin (PRL) from human somatotrophic tumors was examined in vitro. 12-O-tetradecanoyl-phorbol-13- acetate (TPA)strongly stimulated GH and PRL secretion and showed an additive effect on GH secretion if used in combination with GH releasing hormone (GHRH). In contrast, staurosporine exerted a variable inhibitory effect on GH release. There was no correlation between such effects and gsp mutations.The findings suggested that TPA doesn't act directly through cAMP signal transduction system.

The Role of Protein Kinase C and Its Effect on GHRH in the Regulation of Hormone Secretion by Somatotrophinomas / 华中科技大学学报（医学）（英德文版）

Phorbol ester-induced release of growth hormone (GH) and prolactin (PRL) from human somatotrophic tumors was examined in vitro. 12-O-tetradecanoyl-phorbol-13- acetate (TPA)strongly stimulated GH and PRL secretion and showed an additive effect on GH secretion if used in combination with GH releasing hormone (GHRH). In contrast, staurosporine exerted a variable inhibitory effect on GH release. There was no correlation between such effects and gsp mutations.The findings suggested that TPA doesn't act directly through cAMP signal transduction system.

Relationship between the Expression of Growth Hormone-Releasing Hormone Receptor Gene and Endocrinologic Profiles in GH-Secreting Pituitary Adenomas / 대한내분비학회지

BACKGROUND: Growth hormone-releasing hormone (GHRH) plays a key role in the regulation of the proliferation and differentiation of somatomammotroph cells as well as secretion of GH. The actions of GHRH are mediated through the GHRH receptor (GHRH-R) that is a G protein coupled receptor with seven transmembrane domains. It has been demonstrated that alternative splicing occurs in the third cytoplasmic domain of rat and human GHRH-R mRNA, However, the clinical significance of the altemative splicing remains to be unsolved. To find an insight into the clinical significance, we investigate the correlation between the GHRH-R gene expression and a variety of clinical clinical and endocrinological findings in 11 acromegalic patients. METHODS: Eleven acromegalic patients (3 males and 8 females, mean age 43.5 years) were included in this study. Six endocrine tests were carried out to evaluate the GH seeretory function of tumors. Invasiveness of tumors were evaluated by preoperative MRI findings on the basis of Hardys classification. Sequence the gsp oncogene and estimate the GHRH-R gene expression by RT-PCR and in vitro transcription. RESULTS: Three different sized cDNA fragments, 250 bp, 700 bp and 810 bp, were found after RT-PCR. The amount of 250 bp fragment was higher than those of the other two fragments. The clinical findings (age, size, GH level, frequency of paradoxical response to TRH or GnRH, octreotide response, hypothalamic somatostatinergic activity) of the group with high expression of the 250 bp fragment did not significantly differ from those of the group with low expression. The GHRH-R gene expression of tumors with gsp oncogene did not significantly differ from that of tumors without gsp oncogene. CONCLUSION: These results suggest that the expression of GHRH-R gene may not be an important determinant for tumor growth, and the lower GH response to GHRH of tumors with gsp oncogene may not be attributed to the lower expression of GHRH-R gene. The expression of GHRH-R is likely to be regulated by a certain property of tumors for GH secretion and growth.

The effects of testosterone on the response of growth hormone secretion in cultured rat pituitary cells

The effects of testosterone on the pituitary growth hormone (GH) response directly and to hypothalamic growth hormone-releasing hormone (GHRH) were evaluated in vitro using a male pituitary cell monolayer culture system. Wistar male rats were gonadectomized at 22 days of age, and 21 days later their anterior pituitaries were removed and trypsinized for cell dispersion. Testosterone 0, 0.1, 1.0, 10.0 nM was added to the medium for 1 day and GH amounts in media were measured. In another experiment, testosterone 1, 0.1, 1.0, 5.0, 10,0 nM was added to the medioum for 3 days, and subsequently 5 nM GHRH was added for 1 day, thereafter GH amounts in media were measured. The results were as follows: 1) The increase of GH response after testosterone administration to the cultured rat pituitary cell was not significant. 2) The rat pituitary cell response to GHRH was augmented after pretreatment with testosterone. These results are suggested that testosterone has no direct effect on GH secretion, but by increasing the pituitary cell response to GHRH, contributes to the regulation of GH secretion in vitro.

The mechanism of Arginine-stimulated growth hormone secretion

No abstract available.