Growth hormone promotes the reconstruction of injured axons in the hypothalamo-neurohypophyseal system

Previous studies have shown that growth hormone can regulate hypothalamic energy metabolism, stress, and hormone release. Therefore, growth hormone has great potential for treating hypothalamic injury. In this study, we established a specific hypothalamic axon injury model by inducing hypothalamic pituitary stalk electric lesions in male mice. We then treated mice by intraperitoneal administration of growth hormone. Our results showed that growth hormone increased the expression of insulin-like growth factor 1 and its receptors, and promoted the survival of hypothalamic neurons, axonal regeneration, and vascular reconstruction from the median eminence through the posterior pituitary. Altogether, this alleviated hypothalamic injury-caused central diabetes insipidus and anxiety. These results suggest that growth hormone can promote axonal reconstruction after hypothalamic injury by regulating the growth hormone-insulin-like growth factor 1 axis.

Growth hormone improves insulin resistance in visceral adipose tissue after duodenal-jejunal bypass by regulating adiponectin secretion

BACKGROUND The mechanism of improvement of type 2 diabetes after duodenal-jejunal bypass(DJB)surgery is not clear.AIM To study the morphological and functional changes in adipose tissue after DJB and explore the potential mechanisms contributing to postoperative insulin sensitivity improvement of adipose tissue in a diabetic male rat model.METHODS DJB and sham surgery was performed in a-high-fat-diet/streptozotocin-induced diabetic rat model.All adipose tissue was weighed and observed under microscope.Use inguinal fat to represent subcutaneous adipose tissue(SAT)and mesangial fat to represent visceral adipose tissue.RNA-sequencing was utilized to evaluate gene expression alterations adipocytes.The hematoxylin and eosin staining,reverse transcription-quantitative polymerase chain reaction,western blot,and enzyme-linked immunosorbent assay were used to study the changes.Insulin resistance was evaluated by immunofluorescence.RESULTS After DJB,whole body blood glucose metabolism and insulin sensitivity in adipose tissue improved.Fat cell volume in both visceral adipose tissue(VAT)and SAT increased.Compared to SAT,VAT showed more significantly functional alterations after DJB and KEGG analysis indicated growth hormone(GH)pathway and downstream adiponectin secretion were involved in metabolic regulation.The circulating GH and adiponectin levels and GH receptor and adiponectin levels in VAT increased.Cytological experiment showed that GH stimulated adiponectin secretion and improve insulin sensitivity.CONCLUSION GH improves insulin resistance in VAT in male diabetic rats after receiving DJB,possibly by increasing adiponectin secretion.

Aqueous extract of Protaetia brevitarsis larvae increases mTOR-mediated growth rate in zebrafish larvae

Objective:To evaluate the effects of an aqueous extract of Protaetia brevitarsis(AEPB)on the growth of zebrafish and preosteoblast MC3T3-E1 cells.Methods:The effects of AEPB on the linear growth and the expression of growth-related genes in zebrafish and MC3T3-E1 cells were assessed using various molecular techniques.Furthermore,the involvement of the mammalian target of rapamycin(mTOR)pathway in AEPB-induced growth was investigated by employing the mTOR inhibitor rapamycin.Results:AEPB administration led to a significant and dose-dependent increase in zebrafish larvae growth over time.Additionally,AEPB treatment upregulated the expression of growth hormone-1(GH-1),insulin-like growth factor-1(IGF-1),growth hormone receptor-1(GHR-1),and cholecystokinin-a(CCKA)in zebrafish.Similarly,AEPB stimulated the expression and release of IGF-1 and accelerated mTOR expression in MC3T3-E1 cells.In addition,rapamycin hindered AEPB-induced linear growth in zebrafish larvae and suppressed the expression of growth-promoting genes by inhibiting mTOR activation.Conclusions:AEPB shows growth-promoting effects by upregulating growth-related genes and activating the mTOR signaling pathway.Further investigations are warranted to elucidate its mechanisms of action and explore its potential application in the development of growth-enhancing supplements for various purposes.

Effects of different doses of long-acting growth hormone in treating children with growth hormone deficiency

BACKGROUND With the improvement of economy and living standards,the attention paid to short stature in children has been increasingly highlighted.Numerous causes can lead to short stature in children,among which growth hormone deficiency(GHD)is a significant factor.AIM To investigate the long-term efficacy and safety of different doses of long-acting polyethylene glycol recombinant human growth hormone(PEG-rhGH)in the treatment of GHD in children.METHODS We selected 44 pediatric patients diagnosed with GHD who were treated at Wuhu First People's Hospital from 2014 to 2018.Total 23 patients were administered a high dose of long-acting PEG-rhGH at 0.2 mg/kg subcutaneously each week,forming the high-dose group.Meanwhile,21 patients were given a lower dose of long-acting PEG-rhGH at 0.14 mg/kg subcutaneously each week,establishing the low-dose Group.The total treatment period was 2 years,during which we monitored the patients’height,annual growth velocity(GV),height standard deviation score(HtSDS),chronological age(CA),bone age(BA),and serum levels of insulin-like growth factor-1(IGF-1)and insulin-like growth factor-binding protein-3(IGFBP-3)before treatment and at 6 mo,1 year,and 2 years after treatment initiation.We also monitored thyroid function,fasting plasma glucose,fasting insulin,and other side effects.Furthermore,we calculated the homeostatic model assessment for insulin resistance.RESULTS After 1 year of treatment,the GV,HtSDS,IGF-1,BA,and IGFBP-3 in both groups significantly improved compared to the pre-treatment levels(P<0.05).Moreover,when comparing GV,HtSDS,IGF-1,BA,and IGFBP-3 between the two groups,there were no statistically significant differences either before or after the treatment(P>0.05).During the treatment intervals of 0-1.0 years and 1.0-2.0 years,both patient groups experienced a slowdown in GV and a decline in HtSDS improvement(P<0.05).CONCLUSION The use of PEG-rhGH in treating GHD patients was confirmed to be effective,with similar outcomes observed in both the high-dose group and low-dose groups,and no significant differences in the main side effects.

Growth hormone and gastrointestinal malignancy:An intriguing link

Growth hormone(GH)excess is associated with several systemic complications,one of which is the increased risk of neoplastic processes particularly of the gastrointestinal(GI)tract.Among the GI neoplasms,the most reported association is with benign and malignant neoplasms of the colon.In the majority of published literature,an increased incidence of GI neoplasms,both colonic adenomas as well as colorectal carcinoma is reported.However,the studies on colon cancer-specific mortality rate are conflicting with recent studies reporting similar cancer-specific mortality rates in comparison to controls.Many studies have reported an association of colorectal neoplasms with GH levels.Pathogenic mechanisms put forward to explain this association of GH excess and GI neoplasms primarily involve the increased GH-insulin-like growth factor 1(IGF-1)signaling.Both GH and IGF-1 have proliferative,anti-apoptotic,and angiogenic effects on the systemic tissues leading to cellular proliferation.Other contributing factors to the increased risk of GI neoplasms include slow intestinal transit with a redundant large bowel,altered bile acids,deranged local immune response,shared genetic susceptibility factors and hyperinsulinemia.In view of the increased risk association,most guidelines for the care of acromegaly patients recommend an initial screening colonoscopy.Recommendations for further follow-up colonoscopy differ but broadly,the guidelines agree that it depends on the findings at first colonoscopy and state of remission of GH excess.Regarding the concern about the risk of colorectal cancers in patients receiving recombinant GH therapy,most cohort studies do not show an increased risk.

On implications of somatostatin in diabetic retinopathy

Somatostatin,a naturally produced neuroprotective peptide,depresses excitatory neurotransmission and exerts anti-proliferative and anti-inflammatory effects on the retina.In this review,we summarize the progress of somatostatin treatment of diabetic retinopathy through analysis of relevant studies published from February 2019 to February 2023 extracted from the PubMed and Google Scholar databases.Insufficient neuroprotection,which occurs as a consequence of declined expression or dysregulation of retinal somatostatin in the very early stages of diabetic retinopathy,triggers retinal neurovascular unit impairment and microvascular damage.Somatostatin replacement is a promising treatment for retinal neurodegeneration in diabetic retinopathy.Numerous pre-clinical and clinical trials of somatostatin analog treatment for early diabetic retinopathy have been initiated.In one such trial(EUROCONDOR),topical administration of somatostatin was found to exert neuroprotective effects in patients with pre-existing retinal neurodysfunction,but had no impact on the onset of diabetic retinopathy.Overall,we concluded that somatostatin restoration may be especially beneficial for the growing population of patients with early-stage retinopathy.In order to achieve early prevention of diabetic retinopathy initiation,and thereby salvage visual function before the appearance of moderate non-proliferative diabetic retinopathy,several issues need to be addressed.These include the needs to:a)update and standardize the retinal screening scheme to incorporate the detection of early neurodegeneration,b)identify patient subgroups who would benefit from somatostatin analog supplementation,c)elucidate the interactions of somatostatin,particularly exogenously-delivered somatostatin analogs,with other retinal peptides in the context of hyperglycemia,and d)design safe,feasible,low cost,and effective administration routes.

Altered Nutrition State in the Severe Multiple Trauma Patients Undergoing Adjuvant Recombinant Human Growth Hormone Nutritional Support Therapy

In order to observe the nutrition state in the severe multiple trauma patients undergoing adjuvant recombinant human growth hormone (rhGH) nutritional support therapy, 45 patients with severe multiple traumas (ISS>25) were randomly divided into 3 groups. All the 3 groups had been supplied with nitrogen and caloricity according to the need of patients for 16 days. The rhGH therapy started 48 h after surgery and lasted for 14 days in two rhGH-treated groups in which rhGH was 0.2 and 0.4 U/(kg·d) respectively, and the resting group served as control one. The levels of nitrogen balance, prealbumin and safety variables (blood sugar, Na+, TT3 and TT4) were observed and com- pared among the three groups. The levels of nitrogen balance on the postoperative day (POD) 3 and 5 in the rhGH-treated groups were -1.28±3.19, 5.45±2.00 and -0.18±2.55, 6.11±1.60, respectively, which were significantly higher than those in the control group (-5.17±1.68 and -1.08±3.31, P<0.01). The values of prealbumin on the POD 3 and 5 in the rhGH-treated groups were 180.19±27.15, 194.44±50.82 and 194.94±29.65, 194.11±16.17, respectively, which were significantly higher than those in the control group (117.42±19.10 and 135.63±28.31, P<0.01). There was no sig- nificant difference between the rhGH 0.2 U/(kg·d) group and rhGH 0.4 U/(kg·d) group in both of the levels of nitrogen balance and prealbumin. It is concluded that the nutritional support therapy with adjuvant rhGH which starts 48 h after surgery improves the nutrition state of the patients with severe multiple trauma. It is safe for severe multiple trauma patients who accept rhGH at the dose of 0.2 and 0.4 U/(kg·d).

Physiological and pharmacological basis for the ergogenic effects of growth hormone in elite sports

Growth Hormone （GH） is an important and powerful metabolic hormone that is secreted in a pulsatile pattern from cells in the anterior pituitary, influenced by several normal and pathophysiological conditions. Human GH was first isolated in the 1950s and human derived cadaveric GH was initially used to treat patients with GH deficiency. However, synthetic recombinant GH has been widely available since the mid-1980s and the advent of this recombi- nant GH boosted the abuse of GH as a doping agent. Doping with GH is a well-known problem among elite athletes and among people training at gyms, but is forbidden for both medical and ethical reasons. It is mainly the anabolic and, to some extent, the lipolytic effects of GH that is valued by its users. Even though GH＇ s rumour as an effective ergogenic drug among athletes, the effectiveness of GH as a single doping agent has been questioned during the last few years. There is a lack of scientific evidence that GH in supraphysiological doses has additional effects on muscle exercise performance other than those obtained from optimised training and diet itself. However, there might be synergistic effects if GH is combined with, for example, anabolic steroids, and GH seems to have positive effect on collagen synthesis. Regardless of whether or not GH doping is effective, there is a need for a reliable test method to detect GH doping. Several issues have made the development of a method for detecting GH doping complicated but a method has been presented and used in the Olympics in Athens and Turin. A problem with the method used, is the short time span （24-36 hours） from the last GH administration during which the test effectively can reveal doping. Therefore, out-of-competition testing will be crucial. However, work with different approaches to develop an alternative, reliable test is ongoing.

GHRP-6 Induces CREB Phosphorylation and Growth Hormone Secretion via a Protein Kinase Cσ-dependent Pathway in GH3 Cells

This study examined the effect of GHRP-6, a known GHSs receptor agonist, on the phosphorylation of cAMP-responsive element-binding protein （CREB） and the tmderly mechanism. GH3 cells were cultured and subjected to different treatments as follows： GHRP-6, GHRP-6 plus GHRH, phorbol ester （PMA）, an activator of PKC, alone or in combination with GHRP-6, G66983, a general inhibitor of PKCs, in the presence or absence of GHRP-6, rottlerin, an inhibitor of PKCs, alone or plus GHRP-6. The cells were transiently transfected with PKCσ-specific siRNA and then treated with GHRP-6. GH level was measured by enzyme-linked immunosorbent assay （ELISA）. The expression of phosphor-CREB, PKCσ, PKC0 and phosphor-PKCo was determined by Western blotting. The results showed that GHRP-6 stimulated GH secretion in both time- and dose-dependent manners and enhanced the effect of GHRH on GH secretion. GHRP-6 was also found to induce CREB phosphorylation. Moreover, GH secretion was enhanced by the PKC activator PMA and reduced by the PKC inhibitors （G66983, rottlerin） and knockdown of PKCσ. PKCσ could be activated by GHRP-6. It is concluded that PKC, especialiy PKCσ, mediates CREB phosphorylation and GHRP-6-induced GH secretion.

Effect of sericin on diabetic hippocampal growth hormone/insulin-like growth factor 1 axis

Previous studies have shown that sericin extracted from silk cocoon significantly reduces blood glucose levels and protects the nervous system against diabetes mellitus. In this study, a rat type 2 diabetes mellitus model was established by intraperitoneal injection of 25 mg/kg streptozotocin for 3 successive days, following which the rats were treated with sericin for 35 days. After treatment, the blood glucose levels of the diabetic rats decreased significantly, the growth hormone level in serum and its expression in the hippocampus decreased significantly, while the insulin-like growth factor-1 level in serum and insulin-like growth factor-1 and growth hormone receptor expression in the hippocampus increased significantly. The experimental findings indicate that sericin improves disorders of the growth hormone/insulin-like growth factor 1 axis to alleviate hippocampal damage in diabetic rats.

Osteoblast-restricted Disruption of the Growth Hormone Receptor in Mice Results in Sexually Dimorphic Skeletal Phenotypes

Growth hormone （GH） exerts profound anabolic actions during postnatal skeletal development, in part, through stimulating the production of insulin-like growth factor-1 （IGF-1） in liver and skeletal tissues. To examine the requirement for the GH receptor （GHR） in osteoblast function in bone, we used Cre-LoxP methods to disrupt the GHR from osteoblasts, both in vitro and in vivo. Disruption of GHR from primary calvarial osteoblasts in vitro abolished GH-induced signaling, as assessed by JAK2/STAT5 phosphorylation, and abrogated GH-induced proliferative and anti-apoptotic actions. Osteoblasts lacking GHR exhibited reduced IGF-l-induced Erk and Akt phosphorylation and attenuated IGF-1-induced proliferation and anti-apoptotic action. In addition, differentiation was modestly impaired in osteoblasts lacking GHR, as demonstrated by reduced alkaline phosphatase staining and calcium deposition. In order to determine the requirement for the GHR in bone in vivo, we generated mice lacking the GHR specifically in osteoblasts （△GHR）, which were born at the expected Mendelian frequency, had a normal life span and were of normal size. Three week-old, female AGHR mice had significantly reduced osteoblast numbers, consistent with the in vitro data. By six weeks of age however, female AGHR mice demonstrated a marked increase in osteoblasts, although mineralization was impaired; a phenotype similar to that observed previously in mice lacking IGF-1R specifically in osteoblasts. The most striking phenotype occurred in male mice however, where disruption of the GHR from osteoblasts resulted in a ＂feminization＂ of bone geometry in 16 week-old mice, as observed by faCT. These results demonstrate that the GHR is required for normal postnatal bone development in both sexes. GH appears to serve a primary function in modulating local IGF-1 action. However, the changes in bone geometry observed in male AGHR mice suggest that, in addition to facilitating IGF-1 action, GH may function to a greater extent than previously appreciated in establishing the sexual dimorphism of the skeleton.

Amelioration of cognitive impairment following growth hormone replacement therapy:A case report and review of literature

BACKGROUND Stroke is one of the leading causes of death and disability worldwide.In patients suffering from strokes and other acute brain injuries,the prevalence of pituitary dysfunction is high,and growth hormone deficiency is commonly found.Previous studies have demonstrated that administration of recombinant human growth hormone provides adult growth hormone deficiency(AGHD)patients with beneficial effects such as improving body compositions and quality of life.Nevertheless,other physiological benefits of growth hormone substitution are still controversial and inconclusive.CASE SUMMARY A female with a history of hypertension suffered intracranial hemorrhage,intraventricular hemorrhage,and hydrocephalus at 56 years of age.Her mobility,fluency of speech,and mentality were impaired ever since the event occurred.After five years,the 61-year-old patient was further diagnosed with AGHD and received six-month growth hormone replacement therapy(GHRT).After six months of GHRT,the patient’s body composition was improved.A substantial improvement in Mini-Mental State Examination score was also observed,accompanying with ameliorations in mobility,fluency of speech,and mentality.CONCLUSION In addition to improvements in body composition,GHRT for AGHD may provide further beneficial effects in patients with cognitive or motor impairments due to intracerebral hemorrhage.

Clinical and Biochemical Characteristics of Growth Hormone-Secreting Pituitary Tumors

To investigate the difference of biochemical characteristics on gsp positive and gsp negative growth hormone (GH) secreting pituitary tumors, 18 GH secreting pituitary tumors were examined for their clinical characteristics and gsp oncogenes. All patients received the pituitary function combinative stimulating test. It was found that there were no difference in the sex, age, tumor size, course of disease and plasma basal GH levels with gsp positive and gsp negative patients. The plasma levels of PRL were increased in most patients (11/18), and the plasma levels of TSH in gsp positive patients were higher than those in gsp negative patients ( P <0.05). There was no significant difference in the responses to pituitary combinative stimulating test in gsp positive and gsp negative patients. It was concluded that there was little difference in the clinical biochemical characteristics of gsp positive with gsp negative GH secreting pituitary tumors.

The Wingate anaerobic test cannot be used for the evaluation of growth hormone secretion in children with short stature

Purpose: To assess the growth hormone(GH) response to the Wingate anaerobic test(WAn T) among children with short stature and suspected GH deficiency. We hypothesized that the GH response to the WAn T would be similar to the GH response to a commonly used pharmacologic provocation test.Methods: Ten children(6 males and 4 females, age range 9.0–14.9 years) participated in the study. Each participant performed 2 tests: a standard all-out WAn T, cycling for 30 s against constant resistance, and a standardized pharmacologic test(clonidine or glucagon). Blood samples for GH were collected before and 10, 30, 45, and 60 min after the beginning of exercise. In addition, we collected pre-and post-exercise blood lactate levels.Results: There was a significant increase in GH levels after the WAn T, yet in 9 of 10 participants, this increase was below the threshold for GH sufficiency. Peak GH after the WAn T was significantly lower compared to the pharmacologic GH provocation tests(with 9 of 10 demonstrating GH-sufficient response).Conclusion: The traditional WAn T cannot be used as a GH provocation test. Further research is needed to develop anaerobic exercise protocols sufficient to promote GH secretion.

Effect of recombinant human growth hormone and interferon gamma on hepatic collagen synthesis and proliferation of hepatic stellate cells in cirrhotic rats

BACKGROUND: Fibrosis plays a key role in the development of liver cirrhosis. In this study, we investigated the effect of growth hormone and interferon gamma on hepatic collagen synthesis and the proliferation of hepatic stellate cells in a cirrhotic rat model. METHODS: Cirrhosis was induced in rats using carbon tetrachloride. Rats were simultaneously treated with daily subcutaneous injections of recombinant human growth hormone or interferon gamma combined with recombinant human growth hormone. The control group was given saline. The relative content of type I and type IV collagen was assessed by indirect immunofluorescence analysis. Activated hepatic stellate cells were prepared from cirrhotic rats. The 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) method was used to assess the effects of recombinant human growth hormone and interferon gamma on these cells in vitro. RESULTS: Both qualitative and quantitative analysis showed that type I and type IV collagen secretion increased with time after recombinant human growth hormone administration and was significantly higher than control and recombinant human growth hormone combined with interferon gamma administration. In vitro, recombinant human growth hormone significantly stimulated hepatic stellate cell proliferation in a concentration-dependent manner (10 -3 -10 -1 mg/100 μL), andinterferon gamma (10 -2 -10 -1 μg/100 μL) significantly inhibited their growth compared to the control group. Interferon gamma combined with recombinant human growth hormone eliminated this growth-promoting effect to a certain degree in a concentration-dependent manner (10 -1 μg/100 μL, P<0.05, 10 -2 -10 -3 μg/100 μL, P>0.05) and a time-dependent manner (P<0.05). CONCLUSIONS: Recombinant human growth hormone increased collagen secretion in cirrhotic rats in vivo and promoted the proliferation of hepatic stellate cells from cirrhotic rats in vitro. It is possible that concurrent interferon gamma therapy can offset these side-effects of recombinant human growth hormone.

Growth hormone ameliorates hepatopulmonary syndrome and nonalcoholic steatohepatitis secondary to hypopituitarism in a child:A case report

BACKGROUND Craniopharyngioma is a benign tumor that usually develops in children;however,it is located in the center and close to sensitive structures,such as the pituitary gland and hypothalamus.As the hypothalamus plays a crucial role in the homeostasis of anterior pituitary hormone synthesis,damage to the hypothalamus leads to multiple pituitary hormone deficiencies and non-alcoholic fatty liver disease,including hepatopulmonary syndrome(HPS).HPS has limited treatment and poor prognosis.CASE SUMMARY A girl aged 13 years and 6 mo underwent surgery for craniopharyngioma 6 years prior.Right craniotomy was performed with total resection via the corpus callosum approach,and the tumor at the base was approximately 3.5 cm×3.5 cm×4.0 cm.At 1 year postoperatively,she exhibited abdominal distension and weakness,and the laboratory tests revealed fatty liver disease.Thereafter,she had not visited the outpatient clinic for 2 years.Two years ago,she developed decreased activity endurance,severe cyanosis,chest tightness,wheezing,and intermittent and recurrent low fever after mild physical labor.Hepatobiliary ultrasonography,liver biopsy,and contrast echocardiography of the right heart showed cirrhosis and multiple pituitary hormone deficiencies,indicating HPS.After 1 year of treatment with recombinant human growth hormone,the liver function and oxygenation improved;she did not undergo liver transplantation.CONCLUSION Craniopharyngioma surgery can easily cause hypopituitarism,which can lead to nonalcoholic steatohepatitis and HPS in children.Early growth hormone therapy is important to improve the prognosis of these diseases.

Growth hormone cocktail improves hepatopulmonary syndrome secondary to hypopituitarism:A case report

BACKGROUND Metabolic associated fatty liver disease frequently occurs in patients with hypopituitarism and growth hormone(GH)deficiency.Some patients may develop to hepatopulmonary syndrome(HPS).HPS has a poor prognosis and liver transplantation is regarded as the only approach to cure it.CASE SUMMARY A 29-year-old man presented with progressive dyspnea for 1 mo.At the age of 10 years,he was diagnosed with panhypopituitarism associated with pituitary stalk interruption syndrome.Levothyroxine and hydrocortisone were given since then.To achieve ideal height,he received GH treatment for 5 years.The patient had an oxygen saturation of 78%and a partial pressure of arterial oxygen of 37 mmHg with an alveolar–arterial oxygen gradient of 70.2 mmHg.Abdominal ultrasonography showed liver cirrhosis and an enlarged spleen.Perfusion lung scan demonstrated intrapulmonary arteriovenous right-to-left shunt.HPS(very severe)was our primary consideration.His hormonal evaluation revealed GH deficiency and hypogonadotropic hypogonadism when thyroid hormone,cortisol,and desmopressin were administrated.After adding with long-acting recombinant human GH and testosterone for 14 mo,his liver function and hypoxemia were improved and his progressive liver fibrosis was stabilized.He was off the waiting list of liver transplantation.CONCLUSION Clinicians should screen HPS patients'anterior pituitary function as early as possible and treat them primarily with GH cocktail accordingly.

Involvement of PPARs in the regulation of brain CYP2D by growth hormone

OBJECTIVE CYP2D is one of the most abundant subfamily of CYPs in the brain,especially in the cerebellum.Brain CYP2D is responsible for the metabolism of endogenous neurotransmitters such as tyramine and serotonin.Our previous studies have shown brain CYP2D can be regulated by exogenous and endogenous substances with tissue-specificity.The purpose of this study is to examine the effects of cerebral CYP2D on the mice behavior and the regulatory mechanism of brain CYP2D by growth hormone.METHODS Mice received the stereotaxic injection with CYP2D inhibitor quinine in deep cerebellar nuclei of cerebellum.The animals were tested with rotarod apparatus,balance beam,water maze,elevated plus maze and open field.The changes in CYP2D22,PPARαand PPARγ in brain regions and liver were assayed in male growth hormone receptor knockout mice,SH-SY5 Y cells and HepG2 cells.RESULTS The inhibition of cerebellum CYP2D significantly affected the spatial learning and exploring ability of mice.Compared with WT mice,CYP2D expression was lower in brain regions from GHR(-/-)male mice;however,hepatic CYP2D level was similar.Pulsatile GH decreased PPARα m RNA level,and increased m RNA levels of CYP2D6 and PPARα in SH-SY5 Y cells.In HepG2 cells,pulsatile GH resulted in decreases in PPARα and PPARγ m RNA levels,but not CYP2D6.PPARα inhibitor induced CYP2D6 m RNA and protein by 1.32-fold and 1.43-fold in SH-SY5 Y cells.PPARγ inhibitor decreased CYP2D6 m RNA and protein by 74.76% and 40.93%.PPARα agonist decreased the level of CYP2D22 m RNA in liver and cerebellum,while PPARγ agonist rosiglitazone resulted in diametrically increases.The luciferase assay showed that PPARγ actived the CYP2D6 gene promoter while PPARα inhibited its function.Pulsatile GH declined the binding of PPARα with CYP2D6 promoter by 40%,promoted the binding of PPARγ with CYP2D6 promoter by approximate60%.The levels of brain and liver PPARα expression in male GHR(-/-)mice is obviously higher than those in WT mice.The level of PPARγ in male GHR(-/-)mice was decreased in the frontal cortex and hippocampus,while remained stable in the cerebellum and striatum;meanwhile,PPARγ was increased in the liver.CONCLUSION Brain CYP2D may be involved in learning and memory functions of central system.Masculine GH secretion altered the PPARs expression and the binding of PPARs to CYP2D promoter,leading to the elevated brain CYP2D in a tissue-specific manner.Growth hormone may specifically alter the metabolic and synthetic of important endogenous substances in the central nervous system(such as serotonin) through the specific regulation of brain CYP2D expression.

Comparison of Effect of Brassinosteroid and Gibberellin Biosynthesis Inhibitors on Growth of Rice Seedlings

Brassinosteroid（BR） and gibberellin（GA） are two predominant plant hormones that regulate plant cell elongation. Mutants disrupt the biosynthesis of these hormones and display different degrees of dwarf phenotypes in rice. Although the role of each plant hormone in promoting the longitudinal growth of plants has been extensively studied using genetic methods, their relationship is still poorly understood. In this study, we used two specific inhibitors targeting BR and GA biosynthesis to investigate the roles of BR and GA in growth of rice seedlings. Yucaizol, a specific inhibitor of BR biosynthesis, and Trinexapac-ethyl, a commercially available inhibitor of GA biosynthesis, were used. The effect of Yucaizol on rice seedlings indicated that Yucaizol significantly retarded stem elongation. The IC_（50） value was found to be approximately 0.8 μmol/L. Yucaizol also induced small leaf angle phenocopy in rice seedlings, similarly to BR-deficient rice, while Trinexapac-ethyl did not. When Yucaizol combined with Trinexapac-ethyl was applied to the rice plants, the mixture of these two inhibitors retarded stem elongation of rice at lower doses. Our results suggest that the use of a BR biosynthesis inhibitor combined with a GA biosynthesis inhibitor may be useful in the development of new technologies for controlling rice plant height.

Association of growth rate with hormone levels and myogenic gene expression profile in broilers

Background： The growth rate often varies among individual broilers of the same breed under a common management condition. To investigate whether a variation in the growth rate is associated with a difference in hormone levels and myogenic gene expression profile in broilers, a feeding trial was conducted with 10,000 newly hatched Ross 308 chicks in a commercial production facility under standard management. At 38 d of age,30 fast-, 30 medium-, and 30 slow-growing broilers were selected among 600 healthy male individuals. The levels of insulin-like growth factor-1（IGF-1）, triiodothyronine（T3）, thyroxine（T4）, and growth hormone in the serum or breast muscle were assayed by ELISA or RIA kits, and the expression levels of several representative pro-and anti-myogenic genes in the breast muscle were also measured by real-time PCR.Results： Results showed that both absolute and relative weights of the breast muscle were in linear positive correlations with the body weight of broilers（P 〈 0.001）. Fast-growing broilers had higher concentrations of IGF-1 than slow-growing broilers（P 〈 0.05） in both the serum and breast muscle. The serum concentration of T3 was significantly higher in fast-growing birds than in slow-growing birds（P 〈 0.05）. However, no difference was observed in growth hormone or T4 concentration among three groups of birds. Additionally, a decreased expression of an anti-myogenic gene（myostatin） and increased expressions of pro-myogenic genes such as myogenic differentiation factor 1, myogenin, muscle regulatory factor 4, myogenic factor 5, IGF-1, and myocyte enhancer factor 2B, C, and D were observed in fast-growing broilers（P 〈 0.05）, relative to slow-growing broilers.Conclusions： Collectively, these findings suggested that the growth rate is linked to the hormone and myogenic gene expression levels in broiler chickens. Some of these parameters such as serum concentrations of IGF-1 and T3 could be employed to breed for enhanced growth.