共表达生长激素释放激素(GHRH)与垂体腺苷酸环化酶(PACAP)对动物生长的影响

生长激素释放激素(GHRH)与垂体腺苷酸环化酶(PACAP)在序列及功能方面均相似,且同为PACAP/胰高血糖素超家族成员．研究了这二者对生长激素释放的刺激作用,以及对动物生长的影响．构建了3个表达载体,pIRES1- GHRH-PACAP(P-G-P),pIRES1-GHRH(P-G) 及 pIRES1-PACAP(P-P),并转染到CHO细胞中,进行RT-PCR,Dot-ELISA以及Westen-blot检测．此外,给大鼠注射细胞上清表达产物,检测其生物学活性．注射8 h后,注射表达P-G-P上清的大鼠血清中IGF-Ⅰ浓度显著高于其他组(P < 0.05)．用PLGA微球包裹各种质粒,并注射到家兔后肢胫前肌．观察家兔生长情况,并于注射后0,15,30,45天时分别采集家兔血液,检测血液中IGF-Ⅰ浓度．结果显示,三质粒注射组动物体重变化及血液中IGF-Ⅰ浓度均高于对照组．注射后30天时,P-G-P组增重较对照组提高81% (P < 0.01),P-G组比对照组提高15%(P > 0.05),P-P组比对照组高7%(P > 0.05)．另一方面,P-G-P组动物血液中IGF-Ⅰ含量比分别比P-G、P-P及对照组提高16.68% (P > 0.05),17.14%(P > 0.05),50.46%(P < 0.05)．以上结果揭示：给动物注射PLGA微球包裹的共表达GHRH与PACAP质粒,可以增强动物体内生长激素(GH)的分泌,并促进动物生长．通过上述研究发现,肌肉注射PACAP表达质粒可以促进家兔的生长,PACAP和GHRH 共表达可以起到协同作用．这可能为动物的促生长研究提供新的方法．     

PLGA Microsphere-Mediated Growth Hormone Release Hormone Expression Induces Intergenerational Growth

To improve animal growth, growth hormone-releasing hormone (GHRH) expression vectors that maintain constant GHRH expression can be directly injected into muscles. To deliver the GHRH expression vectors, biodegradable microspheres have been used as a sustained release system. Although administering GHRH through microspheres is a common practice, the intergenerational effects of this delivery system are unknown. To investigate the intergenerational effects of polylactic-co-glycolic acid (PLGA) encapsulated plasmid-mediated GHRH supplements, pCMV-Rep-GHRH microspheres were injected into pregnant mice. Growth and expression of GHRH were measured in the offspring. RT-PCR and immunohistochemistry reveal GHRH expression 3–21 days post-injection. The proportion of GH-positive cells in the GHRH treated offspring was 48.2% higher than in the control group (P < 0.01). The GHRH treated offspring were 6.15% (P < 0.05) larger than the control offspring. At day 49 post-injection, IGF-I serum levels were significantly higher in the treatment group than in the control group. This study confirms that intramuscular expression of GHRH mediated by PLGA microspheres significantly enhances intergenerational growth.     

慢病毒载体介导GHRH基因在小鼠肌肉组织表达及对动物生长的影响

人与动物体内生长激素受生长激素释放激素(Growth Hormone Releasing Hormone,GHRH)与生长激素抑制激素(Somatostatin,SST)两种因子共同调节,在体内表达外源GHRH,可以提高体内GH基础水平,进而达到促进体内GH释放,加速动物生长的效果.对慢病毒载体系统加以改造,使之成为C...     

Hypothalamic-pituitary somatotropic function in prepubertal hypothyroid rats: effect of growth hormone replacement therapy.

The effect of thyroid hormone deficiency and growth hormone (GH) treatment on hypothalamic GH-releasing hormone (GHRH)/somatostatin (SS) concentrations, GHRH/SS mRNA levels, and plasma GH and somatomedin-C (IGF-I) concentrations were studied in 28- and 35-day-old rats made hypothyroid by giving dams propylthiouracil in the drinking water since the day of parturition. Hypothyroid rats, at both 28 and 35 days of life, had decreased hypothalamic GHRH content and increased GHRH mRNA levels, unaltered SS content and SS mRNA levels, and reduced plasma GH and IGF-I concentrations. Treatment of hypothyroid rats with GH for 14 days completely restored hypothalamic GHRH content and reversed the increase in GHRH mRNA, but did not alter plasma IGF-I concentrations. These data indicate that, in hypothyroid rats, the changes in hypothalamic GHRH content and gene expression are due to the GH deficiency ensuing from the hypothyroid state. Failure of the GH treatment to increase plasma IGF-I indicates that the feedback regulation on GHRH neurons is operated by circulating GH and/or perhaps tissue but not plasma IGF-I concentrations. Presence of low plasma IGF-I concentrations would be directly related to thyroid hormone deficiency.     

Effect of long-term GHRH and somatostatin administration on GH release and body weight in prepubertal female rats

In order to find a chronic GHRH administration capable of stimulating growth rate without depleting pituitary GH content, prepubertal female rats were subcutaneously (sc) treated with GHRH (1-29)-NH2 and somatostatin (SS). In experiment 1, the rats received sc injections of GHRH and cyclic natural SS for 19 days. In the second study, female rats were continuously treated during 21 days with GHRH, using a slow release pellet, alone or combined with one daily injection of long acting SS (octreotide). In experiment 1, body weight was significantly increased when GHRH was administered at the highest daily dosage (1200 microg/day), accompanied by an slight increment in pituitary GH content. Hypothalamic SS concentrations decreased when GHRH or SS were administered alone whereas the combined treatment with both peptides did not modify this parameter, which suggests the existence of a balance between the chronic actions of both peptides on hypothalamus. In experiment 2, the continuous infusion of GHRH increased plasma GH levels and tended to enhance pituitary GH content. Nevertheless, GHRH effect was not effective enough to increase body weight. By adding one daily injection of SS both GHRH effects on the pituitary gland were abolished. Our study indicates that female rats retain responsiveness to chronic GHRH and SS treatments at both pituitary and hypothalamic levels.     

Investigation of Growth Hormone Releasing Hormone Receptor Structure and Activity Using Yeast Expression Technologies

Abstract

Growth hormone releasing hormone (GHRH) is the positive regulator of growth hormone synthesis and secretion in the anterior pituitary. The peptide confers activity by binding to a seven transmembrane domain G protein-coupled receptor. Signal transduction proceeds through subsequent Gas stimulation of adenylyl cyclase. To investigate ligand/receptor and receptor/G protein associations, the human GHRH receptor was expressed in a modified S. cerevisiae strain which allows for facile measurement of receptor activity by cell prototrophy mediated by a reporter gene coupled to the yeast pheromone response pathway. GHRH-dependent signal activation in this system required the substitution of yeast Gα protein with proteins containing C-terminal regions of Gαs. A D60G variant (analogous to the little mouse mutation) of the receptor failed to respond to agonist. In parallel studies, GHRH₂₉ and the N-terminal extracellular region of the receptor were expressed as Gal4 fusion proteins in a 2-hybrid assay. A specific interaction between these proteins was readily observed. The D60G mutation was engineered into the receptor fusion protein. This protein failed to interact with the ligand fusion, confirming the specificity of the association between unmodified proteins. These two yeast expression technologies should prove invaluable in additional structure/activity analyses of this ligand/receptor pair as well as other peptide ligands and receptors.     

A 66‐bp deletion in growth hormone releasing hormone gene 5′‐flanking region with largemouth bass recessive embryonic lethal

Growth hormone releasing hormone (GHRH) regulates the secretion of growth hormone (GH) in the pituitary gland. A 66‐bp deletion (c.‐923_‐858del) was detected in the 5′‐flanking sequence of the largemouth bass (Micropterus salmoides) GHRH gene. In two cultured random populations of adult individuals (A: n = 170 and B: n = 150), the genotype ratios of +/+:+/? were 2.5:1 and 2.8:1 respectively. Only one ?/? fish was detected. A Largemouth bass family was constructed with two heterozygous individuals (+/?) as parents. The genotype ratio of +/+:+/?:?/? in the filial generation embryos was 1:1.6:0.1 at the neurula and 1:2:0 at hatched larvae stages. This indicated that the 66‐bp deletion was a recessive lethal site and that homozygous individuals (?/?) died off in embryonic development. The growth traits (body weight, body length and body depth) were measured, and the GHRH mRNA expression levels in brain tissue were detected using real‐time PCR. The effects of genotype (+/?) on growth traits and GHRH mRNA expression were not significant. Although the cause of death was not clear, the results hint that the 66‐bp deletion site in GHRH 5′‐flanking sequence significantly affects the livability in largemouth bass embryonic development.     

Masculinization of growth hormone (GH) secretory pattern by dihydrotestosterone is associated with augmentation of hypothalamic somatostatin and GH-releasing hormone mRNA levels in ovariectomized adult rats.

The role of androgen in the sexual dimorphism in hypothalamic growth hormone (GH)-releasing hormone (GHRH) and somatostatin (SS) gene expression was examined in rats. In the first study, the SS and GHRH mRNA levels were measured in both male and female rats at 4, 6, 8, and 10 weeks of age. A significant sex-related difference in the SS and GHRH mRNA levels was observed after 8 weeks of age, when sexual maturation is fully attained. Male rats had higher SS and GHRH mRNA levels than the female rats. In the second study, adult ovariectomized rats received daily injection of dihydrotestosterone (DHT), nonaromatizable testosterone, at a dose of 2 mg/rat for 21 days. The DHT treatment masculinized the GH secretory pattern, which was indistinguishable from that of intact male rats, and simultaneously augmented the SS and GHRH mRNA levels. The DHT treatment of ovariectomized rats after hypophysectomy significantly raised the level of SS mRNA, but not that of GHRH mRNA compared to the control animals. These findings suggest that the activation of the SS gene expression through androgen receptor plays an important role in the maintenance of sexual dimorphism in GH secretion in rats.     

Insights into a role of GH secretagogues in reversing the age-related decline in the GH/IGF-I axis

Growth hormone (GH) secretion and serum insulin-like growth factor-I (IGF-I) decline with aging. This study addresses the role played by the hypothalamic regulators in the aging GH decline and investigates the mechanisms through which growth hormone secretagogues (GHS) activate GH secretion in the aging rats. Two groups of male Wistar rats were studied: young-adult (3 mo) and old (24 mo). Hypothalamic growth hormone-releasing hormone (GHRH) mRNA and immunoreactive (IR) GHRH dramatically decreased (P < 0.01 and P < 0.001) in the old rats, as did median eminence IR-GHRH. Decreases of hypothalamic IR-somatostatin (SS; P < 0.001) and SS mRNA (P < 0.01), and median eminence IR-SS were found in old rats as were GHS receptor and IGF-I mRNA (P < 0.01 and P < 0.05). Hypothalamic IGF-I receptor mRNA and protein were unmodified. Both young and old pituitary cells, cultured alone or cocultured with fetal hypothalamic cells, responded to ghrelin. Only in the presence of fetal hypothalamic cells did ghrelin elevate the age-related decrease of GH secretion to within normal adult range. In old rats, growth hormone-releasing peptide-6 returned the levels of GH and IGF-I secretion and liver IGF-I mRNA, and partially restored the lower pituitary IR-GH and GH mRNA levels to those of young untreated rats. These results suggest that the aging GH decline may result from decreased GHRH function rather than from increased SS action. The reduction of hypothalamic GHS-R gene expression might impair the action of ghrelin on GH release. The role of IGF-I is not altered. The aging GH/IGF-I axis decline could be rejuvenated by GHS treatment.     

Changes in the hypothalamic-pituitary somatotropic function of infant hypothyroid rats

The effects of the perturbation of the pituitary-thyroid axis induced during development on the functional activity of the growth hormone (GH) regulatory neuronal systems, GH-releasing hormone (GHRH), and somatostatin (SS) were studied in 14- and 21-day-old rats made hypothyroid by giving dams propylthiouracil in the drinking water since the day of parturition. Infant hypothyroid rats, both at 14 and 21 days of life, had elevated plasma thyroid-stimulating hormone levels and decreased pituitary and plasma GH levels. Simultaneous determination of hypothalamic GHRH/SS-like immunoreactivity (LI) and GHRH/SS mRNA levels did not reveal any difference in 14-day-old hypothyroid rats when compared with age-matched controls. In contrast, 21-day-old hypothyroid rats had decreased GHRH-LI content and a striking rise in GHRH mRNA levels, whereas SS-LI content and SS gene expression remained unaltered. These data indicate that in infant hypothyroid rats, changes in the functional activity of the GHRH neuronal system occur later than changes in GH secretion and are probably dependent on the GH deficiency. The functional activity of SS neurons was apparently unaltered in these hypothyroid rats, pointing to a lesser sensitivity of this system to the perturbation of the pituitary-thyroid axis.     

Overexpression of GRF Encapsulated in PLGA Microspheres in Animal Skeletal Muscle Induces Body Weight Gain

Biodegradable nanospheres or microspheres have been widely used as a sustained release system for the delivery of bioagents. In the present study, injectable sustained-release growth hormone-releasing factor (GRF) (1–32) microspheres were prepared by a double emulsion-in liquid evaporation process using biodegradable polylactic-co-glycolic acid (PLGA) as the carrier. The entrapment efficiency was 89.79% and the mean particle size was 4.41 μm. The microspheres were injected into mouse tibialis muscle. After 30 days, mice injected with GRF (1–32) microspheres (group I) gained significantly more weight than any other treatment group, including mice injected with the naked plasmid (group II) (10.26 ± 0.13 vs. 9.09 ± 0.56; P < 0.05), a mixture of microspheres and plasmid (group III) (10.26 ± 0.13 vs. 8.57 ± 0.02; P < 0.05), or saline (IV) (10.26 ± 0.13 vs. 6.47 ± 0.26; P < 0.05). In addition, mice treated with the GRF (1–32) microspheres exhibited the highest expression levels of GRF as detected by PCR, RT-PCR, and ELISA (mean 2.56 ± 0.40, P < 0.05, overall comparison of treatment with groups II, III, and IV). Additionally, rabbits were injected in the tibialis muscle with the same treatments described above. After 30 days, the group treated with GRF (1–32) microspheres gained the most weight. At day 30 postinjection, weight gain in group I was 63.93% higher than group II (plasmid) (877.10 ± 24.42 vs. 535.05 ± 26.38; P < 0.05), 108.59% higher than group III (blank MS) (877.10 ± 24.42 vs. 420.50 ± 19.39; P < 0.05), and 93.94% higher than group IV (saline) (877.10 ± 24.42 vs. 452.25 ± 27.38; P < 0.05). Furthermore, IGF-1 levels in the serum from GRF microsphere-treated group were elevated relative to all other groups. The present results suggest that encapsulation of GRF with PLGA increases GRF gene expression in muscle after local plasmid delivery, and stimulates significantly more weight gain than delivery of the naked plasmid alone.     

Chronic upper airway resistive loading induces growth retardation via the GH/IGF-I axis in prepubescent rats.

The effect of upper airway loading on longitudinal bone growth and various components of the growth hormone (GH)/insulin-like growth factor I (IGF-I) axis has not been fully elucidated. In the present study, the effect of chronic resistive airway loading (CAL) in a prepubescent rat model on linear bone growth and weight gain was investigated. We hypothesize that CAL induced in prepubescent rats will lead to impaired longitudinal growth due to impairment in circulating and liver GH/IGF-I parameters. The tracheae of 22-day-old rats were obstructed by tracheal banding to increase inspiratory esophageal pressure. The GH/IGF-I markers were analyzed using ELISA, RT-PCR, and Western immunoblot analysis 14 days after surgery. Animals exhibited impaired longitudinal growth as demonstrated by reduction of tibia and tail length gains by 40% (P < 0.0001) and body weight gain by 24% (P < 0.0001). No differences were seen in total body energy balance, i.e., oxygen consumption, daily food intake, or arterial blood gases. Circulating GH, IGF-I, and IGF binding protein-3 (IGFBP-3) levels were reduced by 40% (P = 0.037), 30% (P < 0.006), and 27% (P = 0.02), respectively, in the CAL group. Liver IGF-I mRNA level decreased by 20% (P < 0.0002), whereas GH receptor mRNA and protein expression were unchanged. We conclude that impaired longitudinal growth in prepubescent CAL rats is related to a decrease in GH, IGF-I, and IGFBP-3 levels.     

Two Novel Coding SNPs of SREBP1c Gene are Associated with Body Weight and Average Daily Gain in Bovine

It is known that the SREBP1c gene is an important gene responsible for adipogenesis and regulation of the expression of genes controlling fatty acid biosynthesis. Its expression levels increase in parallel with obesity. Therefore, the present study focused on screening the genetic variation within bovine SREBP1c gene and analyzing its effect on growth traits in 1035 individuals belonging to four Chinese cattle breeds (QC, NY, JX, CH) using PCR-SSCP, DNA sequencing, and forced PCR-RFLP methods. The results revealed two novel mutations: NC_007317: g. 10781 C > A (457aa), 10914 G > A (502aa). Association analysis with growth traits in the Nangyang breed indicated that: The SNPs in the bovine SREBP1c gene had significant effects on body weight and average daily gain at birth, 6 and 12 months old (P < 0.05 or P < 0.01). Therefore, these results suggest that the SREBP1c gene is a strong candidate gene that affects growth traits in cattle.     

Influence of estrogen administration on the growth response to growth hormone (GH) in GH-deficient mice

In women who are growth hormone (GH) deficient, exogenous estrogens increase the dosage of GH that is needed to normalize circulating levels of insulin-like growth factor (IGF-1). Serum IGF-1 derives mostly from the liver, and it is unknown whether the peripheral effects of GH are also impaired by estrogens. Because the ultimate effect of GH is longitudinal growth, we have investigated the influence of estrogen administration on the growth response to recombinant mouse GH therapy in prepubertal GH-deficient (GHD) GHRH knockout (GHRHKO) female mice. Twenty-four GHRHKO female mice (4 animals/group) were treated for 4 weeks (from the second to sixth week of age) with the following schedules: Group I, GH only (25 microg/day); Group II, subcutaneous (sc) ethynil estradiol (EE) (0.035 ES01247g/day); Group III, GH + scEE; Group IV, oral (po) EE (0.035 microg/day); Group V, GH + poEE; Group VI, placebo. At the end of the treatment period, we measured uterine weight, total body weight (TBW), body length (nose-anus, N-A), and femur length. In addition, serum IGF-1 levels were measured. Uteri of mice treated with oral or scEE showed similar increases in weight. There was no difference in the increase in longitudinal growth parameters between mice treated with GH alone or with GH in association with oral or scEE. Serum IGF-1 decreased in animals treated with GH + scEE, compared with GH group, but no group was significantly different from placebo. These results show that subcutaneous or oral EE does not reduce the growth response to GH in female GHD mice.     

Induction of growth hormone (GH) mRNA by pulsatile GH-releasing hormone in rats is pattern specific

Growth hormone-releasing hormone (GHRH) is a main inducer of growth hormone (GH) pulses in most species studied to date. There is no information regarding the pattern of GHRH secretion as a regulator of GH gene expression. We investigated the roles of the parameters of exogenous GHRH administration (frequency, amplitude, and total amount) upon induction of pituitary GH mRNA, GH content, and somatic growth in the female rat. Continuous GHRH infusions were ineffective in altering GH mRNA levels, GH stores, or weight gain. Changing GHRH pulse amplitude between 4, 8, and 16 microg/kg at a constant frequency (Q3.0 h) was only moderately effective in augmenting GH mRNA levels, whereas the 8 microg/kg and 16 microg/kg dosages stimulated weight gain by as much as 60%. When given at a 1.5-h frequency, GHRH doubled the amount of GH mRNA, elevated pituitary GH stores, and stimulated body weight gain. In the rat model, pulsatile but not continuous GHRH administration is effective in inducing pituitary GH mRNA and GH content as well as somatic growth. These studies suggest that the greater growth rate, pituitary mRNA levels, and GH stores seen in male compared with female rats are likely mediated, in part, by the endogenous episodic GHRH secretory pattern present in males.     

Effects of acute intravenous injection of two growth hormone-releasing hormones (GHRH 1-40 and 1-29) on serum growth hormone and other pituitary hormones in short children with pulsatile growth hormone secretion

We administered two different growth hormone-releasing hormones (GHRH) to 20 short, prepubertal children who had spontaneous secretion of growth hormone (GH), assessed from 24-hour GH secretion profiles (72 sampling periods of 20 min). We compared one i.v. injection of 1 microgram/kg of GHRH 1-40 with that of GHRH 1-29 regarding serum concentrations of GH, prolactin, luteinizing hormone, follicle-stimulating hormone and IGF-I. The children were allocated to two groups without statistical randomization. Both groups were given both peptides, with at least 1 week in between. The first group started with GHRH 1-40, the other with GHRH 1-29. The peptides both induced an increased serum concentration of GH of the same magnitude: mean maximal peak of 89 +/- 12 mU/l after GHRH 1-40 and 94 +/- 10 mU/l after GHRH 1-29 (n.s.). The mean difference in maximum serum GH concentration in each child after injection was 52 +/- 9 mU/l, range 1-153 mU/l. GHRH 1-29 also induced a short-term, small increase in the concentrations of prolactin (p less than 0.05), luteinizing hormone (p less than 0.01) and follicle-stimulating hormone (p less than 0.05). We conclude that the shorter sequence GHRH 1-29, when given in a dose of 1 microgram/kg, gives a rise in serum concentration of GH similar to that after the native form GHRH 1-40.     

GH responses to GHRH and GHRP-6 in Streptozotocin (STZ)-diabetic rats

GH responses to GHRH, the physiologic hypothalamic stimulus, and GHRP-6, a synthetic hexapeptide that binds the Ghrelin receptor, were studied in rats treated with streptozotocin (STZ), an experimental model of diabetes. Sprague-Dawley male rats received a single injection either of STZ (70 mg/Kg in 0.01 M SSC, i.p.) or of the vehicle (0.01 M SSC). GH responses were challenged with two different doses of GHRH (1 and 10 microg/kg) or GHRP-6 (3 and 30 microg/kg) and with a combination of both at low (1 + 3 microg/kg) or high (10 + 30 microg/kg) doses, respectively. We observed a dose-dependent effect for GH responses to GHRH both in STZ-treated rats and in controls. However, we could not find significant differences between STZ-rats and controls. GH responses to GHRP-6 occurred in a dose-dependent manner in STZ-rats, but not in controls. GH responses to GHRP-6 in both groups were clearly lower than those elicited by GHRH. GH responses to 30 microg/Kg of GHRP-6 were significantly greater in STZ-rats than in controls (AUC: 3549.9 +/- 1001.4 vs. 2046.4 +/- 711.7; p<0.05). The combined administration of GHRH plus GHRP-6 was the most potent stimuli for GH in both groups. The administration of doses in the lower range (1 + 3 microg/Kg, GHRH + GHRP-6 respectively) induced a great peak of GH in STZ-rats and in control rats, revealing a synergistic effect of GHRH and GHRP-6 in both groups. When the higher doses were administered (10 + 30 microg/kg), GH levels in time 5, and AUC were significantly higher in control rats. In addition, a negative correlation between WT (weight tendency) values and GH responses, represented as AUC, could be established in STZ-rats (r2=-0.566, p=0.004 for GHRH; r2=-0.412, p=0.028 for GHRP-6). Thus, the more negative the values of WT were, the more severe the metabolic alteration and, therefore, the higher the GH response to GHRH and GHRHP-6. In conclusion, our results do not support the existence of a functional hypothalamic hypertone of SS in diabetic rats, as GH responses were not usually reduced in STZ-rats, except when both secretagogues were administered together at the higher doses. Besides, GH responses to GHRH and GHRP-6 were inversely correlated with the severity of the metabolic alteration in STZ-rats, meaning that worse glycaemic control promoted higher GH secretion. These results resemble those found in humans, where GH responses to secretagogues are increased in type-1 diabetes and depend on hyperglycaemia, and are representative of not well-controlled insulin-dependent diabetic status.     

Effect of High Dietary Copper on Somatostatin and Growth Hormone-Releasing Hormone Levels in the Hypothalami of Growing Pigs

This experiment was conducted to examine the effect of dietary copper supplementation on somatostatin (SS) and growth hormone-releasing hormone (GHRH) mRNA expression levels in the hypothalami of growing pigs. A total of 45 crossbred pigs were randomly assigned to three groups of 15 pigs each; five replicates of three animals comprised each group. Pigs were allocated to diets that contained 5 mg/kg copper (control), 125 mg/kg copper sulfate, or 125 mg/kg copper methionine. At the end of the experiment, five pigs were selected at random from each group and slaughtered, and hypothalami were collected for determination of SS and GHRH mRNA expression levels. The results showed that the SS expression levels were lower and the GHRH levels were higher in pigs fed the diets with 125 mg/kg copper methionine (P < 0.05) and 125 mg/kg copper sulfate (P < 0.05), respectively, than in pigs fed the diet with 5 mg/kg copper. Furthermore, the relationship between SS mRNA and GHRH mRNA abundance had a significantly negative correlation (P < 0.05). The data indicated that high dietary copper could enhance GHRH mRNA expression levels and suppress SS mRNA expression levels in the hypothalami of pigs. High lever dietary copper (125 mg/kg copper sulfate or 125 mg/kg copper methionine) increased pigs’ growth performance and feed efficiency but had no significant effect on daily feed intake; 125 mg/kg copper sulfate or 125 mg/kg copper methionine at the same lever had no difference on growth promoting in pigs.