Developmental programming:the role of growth hormone

Developmental programming of the fetus has consequences for physiologic responses in the offspring as an adult and,more recently,is implicated in the expression of altered phenotypes of future generations.Some phenotypes,such as fertility,bone strength,and adiposity are highly relevant to food animal production and in utero factors that impinge on those traits are vital to understand.A key systemic regulatory hormone is growth hormone(GH),which has a developmental role in virtually all tissues and organs.This review catalogs the impact of GH on tissue programming and how perturbations early in development influence GH function.     

Growth hormones therapy in immune response against Trypanosoma cruzi

Growth hormone (GH) is an important hypophyseal hormone that is primarily involved in body growth and metabolism. In mammals, control of Trypanosoma cruzi parasitism during the acute phase of infection is considered to be critically dependent on direct macrophage activation by cytokines. To explore the possibility that GH might be effective in the treatment of Chagas’ disease, we investigated its effects on the course of T. cruzi infection in rats, focusing our analyses on its influences on parasitemia, NO, TNF-α and IFN-γ concentration and on histopathological alterations and parasite burden in heart tissue. T. cruzi-infected male Wistar rats were intraperitoneally treated with 5 ng/10 g body weight/day of GH. Animals treated with GH showed a significant reduction in the number of blood trypomastigotes during the acute phase of infection compared with untreated animals (P < 0.05). For all experimental days (7, 14 and 21 post infection) of the acute phase, infected and GH treated animals reached higher concentrations of TNF-α, IFN-γ and nitric oxide as compared to untreated and infected counterparts (P < 0.05) Histopathological observations of heart tissue revealed that GH administration also resulted in fewer and smaller amastigote burdens, and less inflammatory infiltrate and tissue disorganization, indicating a reduced parasitism of this tissue. These results show that GH can be considered as an immunomodulator substance for controlling parasite replication and combined with the current drug used may represent in the future a new therapeutic tool to reduce the harmful effects of Chagas’ disease.     

生长激素受体介导的信号转导机制研究进展

生长激素(growth hormone,GH)对动物的生长发育具有重要的生理作用.GH与生长激素受体(growth hormone receptor,GHR)结合后才会发挥一系列的生理作用.近年来,人们对GHR结构和功能的研究取得了巨大的进展,并取得了一些重大的突破.现在已清楚了GH-GHR轴激活一些相关的信号转导通路,但并非所有的通路都依赖酪氨酸激酶.作者从以下几个方面总结了GHR作用下的信号转导机制的研究进展:GHR的结构与功能;依赖JAK2的相关信号通路;不依赖JAK2的相关信号通路;GHR信号负调控因子.阐明这些复杂机制,对进一步了解GH对动物不同的生理和病理作用具有重要意义.     

Growth Hormone and Prolactin Secretion in Horses: Effects of Multiple and Extended Exercise Bouts, β-Hydroxy-β-Methyl Butyrate Feeding,and Arginine and Thyrotropin-Releasing Hormone Pretreatment

Five experiments were performed to test the overall hypothesis that exercise might be a useful indicator of growth hormone (GH) and prolactin status in horses. In experiment 1, geldings were exercised for 5 minutes four times at hourly intervals. The prolactin response (P < .05) to the first two exercise bouts was small and increased with successive bouts. There was a consistent GH response (P < .05) for only the first two bouts. In experiment 2, geldings were exercised for 29 to 39 minutes on a treadmill. After the initial bout, half the geldings were supplemented daily with Ca-β-hydroxy-β-methyl butyrate, and all geldings were conditioned for 12 weeks. Exercise bouts at 7 and 12 weeks indicated no effect (P > .1) of supplementation. In experiment 3, treatment of geldings with arginine before exercise increased (P < .001) prolactin concentrations but had no effect (P > .1) on the GH response to exercise. In experiment 4, the repeatability of the GH response to 5 minutes of exercise was determined by exercising eight stallions on six separate occasions. In addition to a large variation in GH response among stallions, there was a large variation within each stallion. In experiment 5, pretreatment with thyrotropin-releasing hormone 2 hours before exercise did not normalize the GH response to exercise. In conclusion, factors affecting the GH response to exercise likely preclude its usefulness as an indicator of GH status in horses.     

Ghrelin differentially modulates the GH secretory response to GHRH between the fed and fasted states in sheep

The effect of energy balance on the growth hormone (GH) secretory responsiveness to growth hormone-releasing hormone (GHRH) has not been determined in ruminant animals. Therefore, we examined the effects of intravenous injections of 0, 3.3, and 6.6 μg ghrelin/kg body weight (BW), with and without GHRH at 0.25 μg/kg BW, on GH secretory responsiveness in both the fed and fasted sheep. The injections were carried out at 48 h (Fasting state) and 3 h (Satiety state) after feeding. Blood samples were taken every 10 minutes, from 30 minutes before to 120 minutes after the injection. Low (3.3 μg/kg BW) and high (6.6 μg/kg BW) doses of ghrelin stimulated GH secretion significantly (P < .05) greater in the Satiety state than in the Fasting state. Growth hormone-releasing hormone plus both doses of ghrelin stimulated GH secretion significantly (P < .05) greater in the Satiety state than in the Fasting state. Ghrelin and GHRH exerted a synergistic effect in the Satiety state, but not in the Fasting state. Plasma ghrelin levels were maintained significantly (P < .05) greater in the Fasting state than in the Satiety state except the temporal increases after ghrelin administration. Plasma free fatty acid (FFA) concentrations were significantly (P < .01) greater in the Fasting state than in the Satiety state. In conclusion, the present study has demonstrated for the first time that ghrelin differentially modulates GH secretory response to GHRH according to feeding states in ruminant animals.     

Responses of Adenohypophyseal Hormones to Substance P Administration in Geldings: Comparison to Responses After Brief Exercise and Sulpiride Administration

Nine adult geldings were used in three experiments to study the possible role of substance P in the prolactin responses to nondopaminergic stimuli. Experiment 1 was performed as an incomplete Latin square design to determine the secretory responses of prolactin, growth hormone (GH), adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) to IV administration of substance P. Doses tested and compared to no peptide (0 dose, control) were 62, 125, 250, and 500 μg of substance P. The three highest doses of peptide caused an immediate rise in heart rate, sweating, salivation, rhinorrhea, stretching of hind legs, and defecation. The lowest dose (62 μg) caused minor sweating, some rhinorrhea, and a rise in heart rate. Recovery from these physical responses was complete in approximately 30 minutes. All doses of substance P caused an immediate rise (P < .01) in plasma prolactin concentrations, with the three highest doses producing similar responses, and the 62 μg dose producing a minimal response (P < .05). Concentrations of ACTH (P < .01) and GH (P = .05) also increased after substance P administration; concentrations of LH, FSH, and TSH were unaffected. Experiment 2 compared the effects of brief exercise on hormonal characteristics. Two minutes of trotting increased (P < .01) plasma concentrations of GH, ACTH, and prolactin, as well as LH (P = .055). Experiment 3 determined the relative responses of prolactin to a fixed dose of sulpiride (0.1 mg/kg of body weight). In general, the prolactin responses to substance P were similar to those after exercise, which were both generally less than after sulpiride. These data are consistent with a possible role of substance P in the prolactin response to stressful stimuli.     

Endocrine modulation of physiological responses to catabolic disease

Disease or endotoxemia alters the plasma concentrations of anabolic hormones, particularly growth hormone (GH) and insulin-like growth-factor I (IGF-I). In general, these hormones are inhibited during the catabolic disease state. A hypothesis has evolved that anabolic hormones might be useful in patients’ recovery under these and other catabolic circumstances. The treatment of cattle with GH has provided significant improvement in the physiological response of the animals to the subsequent injection of bacterial lypopolysaccharide (LPS), perhaps via inhibition of tumor necrisis factor (TNF) release. However, this improved response to disease was not observed with animals treated with GH and infected with one of two parasitic organisms, Sarcocystis cruzi or Eimeria bovis. Recent attempts with other anabolic hormones, estradiol and progesterone, have proven remarkably effective in improving the adaptive physiological responses of calves to either E. bovis infection or to the injection of LPS. All animals displayed signs of infection, but the intensity and duration of symptoms were reduced. Although a mechanism is not yet known, there were no effects on TNF; cortisol; the percentages of lymphocytes expressing CD2, 4, or 8 antigens; or the production of antibodies.     

A proteomic analysis of the effect of growth hormone on mammary alveolar cell-T (MAC-T) cells in the presence of lactogenic hormones

The bovine mammary alveolar cell-T (MAC-T) cell line is able to uniformly differentiate and secrete casein proteins in response to dexamethasone, insulin, and prolactin and is extensively used to study bovine mammary epithelial cell (MEC) function. Somatotropin, or growth hormone (GH), has been shown to increase milk protein synthesis both in vivo and in mammary cell models and to induce cytoskeletal rearrangement in a 3T3 fibroblast cell line and a Chinese hamster ovary cell line. To identify the nature of the effects of GH in MECs cultured with lactogenic hormones, changes in global protein expression were assessed in the MAC-T cell line with the use of two-dimensional gel electrophoresis and matrix-assisted laser desorption ionization tandem time of flight mass spectrometry. Forty proteins were differentially expressed in response to GH (P < 0.05) and were related to metabolism, the cytoskeleton, protein folding, RNA and DNA processing, and oxidant stress. These widespread changes in protein expression are indicative of a global role of GH in overall cellular differentiation that may underlie the direct modulation of milk component synthesis in MEC models that have been described to date.     

Effects of parachlorophenylalanine,quipazine and cyproheptadine on growth hormone and adrenocorticotropin secretion in steers

Adrenergic and perhaps dopaminergic neurons provide inhibitory regulation of growth hormone (GH) secretion in ruminants. This suggests that either serotonergic or other neurons regulate the stimulatory release of GH. The nature of neurotransmitter control of adrenocorticotropin (ACTH) secretion in ruminants has not been determined. Parachlorophenylalanine (PCPA; serotonin synthesis inhibitor), quipazine (serotonin receptor agonist) and cyproheptadine (serotonin receptor antagonist) were utilized in Holstein steers to determine whether serotonin receptors mediate stimulatory actions on GH and ACTH secretion. PCPA (100 mg/kg BW) administered each day at 1900 hr for three successive days did not alter mean GH concentrations, amplitude of GH peaks, nor the number of GH peaks. Likewise, PCPA altered none of these parameters for ACTH. Quipazine injected iv at .1 or .5 mg/kg BW increased plasma GH (P<.05) and ACTH (P<.001) concentrations. There was a dose effect of quipazine on both GH (P<.05) and ACTH (P<.001) secretion. Pretreatment of steers with cyproheptadine (.06 and .6 mg/kg BW) reduced the stimulation of GH by quipazine (P<.0001) and decreased basal GH concentrations (P<.0004). Cyproheptadine at .06 mg/kg BW did not alter quipazine effects on ACTH, however, the higher dose decreased the peak ACTH response (P<.02) to quipazine. Studies with quipazine and cyproheptadine indicated that serotonergic mechanisms are likely involved in the regulation of GH and ACTH secretion in steers.     

Somatotropin response in vitro to corticosterone and triiodothyronine during chick embryonic development: Involvement of type I and type II glucocorticoid receptors

Corticosterone (CORT) can stimulate growth hormone (GH) secretion on embryonic day (e) 12 in the chicken. However, CORT failed to induce GH secretion on e20 in a single report, suggesting that regulation of GH production changes during embryonic development. Secretion in response to CORT during embryonic development is modulated by the thyroid hormones triiodothyronine (T₃) and thyroxine (T₄). Growth hormone responses on e12 involve both glucocorticoid (GR) and mineralocorticoid receptors (MR); however, involvement of MR has not been evaluated past e12. To further define changes in somatotroph responsiveness to CORT, pituitary cells obtained on e12–e20 were cultured with CORT alone and in combination with T₃ and GH-releasing hormone (GHRH). Growth hormone mRNA levels and protein secretion were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and radioimmunoassay (RIA), respectively. Corticosterone significantly increased GH mRNA and protein secretion on e12; however, mRNA concentration and protein secretion were unaffected on e20. Contributions of GR and MR in CORT responses were evaluated using GR and MR antagonists. Treatment with a GR-specific antagonist effectively blocked the CORT-induced increase in GH secretion on e12. The same treatment on e20 had no effect on GH secretion. These findings demonstrate that GR is directly involved in glucocorticoid stimulation of GH secretion at the time of somatotroph differentiation but is not regulatory at the end of embryonic development. We conclude that positive somatotroph responses to CORT are lost during chicken embryonic development and that GR is the primary regulator of CORT-induced GH secretion.     

The role of the somatotrophic axis in the metabolism of the chicken.

As it is for mammalian species, growth hormone (GH) is indispensable for normal growth and development of avian species. In contrast to mammals, exogenous GH administration has little, if any, potential for improving the growth rate and feed efficiency of rapidly growing broilers; it is more likely to do so in older birds. This is at least partly because of age-related changes in tissue GH-binding activity and GH-receptor mRNA expression. The effects of GH on lipid deposition depends on the age of the bird and pattern of GH administration. Pulsatile, but not continuous, GH administration to older broilers seems to reduce fat deposition. As in rats, the bioactivity of GH might also depend on the pulse-induced cyclicity in GH receptors and GH-binding proteins. In chickens, GH is also a very potent lipolytic hormone, but seems to have no diabetogenic effect, which is reported in mammalian species. Both insulin-like growth factors have apparently no growth-promoting effects in normal growing broilers, but seem to have opposite effects on fat deposition. In contrast to GH, both insulin-like growth factors have a marked hypoglycemic effect. Whether all these effects are direct effects, or are mediated by secondary mechanisms, awaits further investigations.     

Secretory patterns of growth hormone and insulin-like growth factor-I during peripubertal period in intact and castrate male cattle

Fifteen Angus bulls and 15 Angus steers 9 months of age and 275 kg of body weight were bled at 20-min intervals over a 6-hr period and serum GH and IGF-I concentrations were measured by RIA. There were no differences between bulls and steers in the mean GH concentration, pulse frequency and amplitude when analyzed by the computer program PULSAR. Mean IGF-I concentration was not different between the two sex phenotypes, nor was there a significant correlation between the integrated IGF-I and GH concentrations. Subsequently, five bulls and five steers were selected from the 30 animals, full-fed a diet for growth in individual pens for 3 months and bled at 15-min intervals over a 24-hr period. Bulls tended to show a greater weight gain and feed conversion efficiency (P<.10) than steers during the 3-month period. Serum GH concentrations had a pulsatile pattern in all animals with no apparent diurnal rhythm during the 24-hr bleeding. Although mean GH concentration was not different between the two sex phenotypes, bulls tended to have lower baseline levels (P<.10) and greater peak amplitudes than steers. Serum IGF-I concentrations fluctuated within a two-fold concentration range, with no obvious pulsatility similar to that of GH. Mean IGF-I concentrations of each of the 10 animals were correlated with mean peak GH amplitudes (r = .79), but not with mean GH. These results suggest that gonadal hormone(s) modulates the GH secretory pattern and increases IGF-I secretion which may be related to the greater growth rate of bulls compared with steers.     

High glycemic and insulinemic responses to meals affect plasma growth hormone secretory characteristics in Quarter Horse weanlings

Growth hormone is a key component of the somatotropic axis and is critical for the interplay between nutrition, regulation of metabolic functions, and subsequent processes of growth. The objective of this study was to investigate potential relations between meal feeding concentrates differing in the glycemic responses they elicit and GH secretory patterns in young growing horses. Twelve Quarter Horse weanlings (5.4 ± 0.4 mo of age) were used in a crossover design, consisting of two 21-d periods and two treatments, a high-glycemic (HG) or low-glycemic (LG) concentrate meal, fed twice daily. Horses were individually housed and fed hay ad libitum. On the final day of each period, quarter-hourly blood samples were drawn for 24 h to measure plasma glucose, insulin, non-esterified fatty acids, and GH. Growth hormone secretory characteristics were estimated with deconvolution analysis. After a meal, HG-fed horses exhibited a longer inhibition until the first pulse of GH secretion (P = 0.012). During late night hours (1:00 AM to 6:45 AM), HG horses secreted a greater amount of pulsatile GH than LG horses (P = 0.002). These differences highlight the potential relations between glycemic and insulinemic responses to meals and GH secretion. Dietary energy source and metabolic perturbations associated with feeding HG meals to young, growing horses have the potential to alter GH secretory patterns compared with LG meals. This may potentially affect the developmental pattern of various tissues in the young growing horse.     

生长激素激活受体机理的研究进展

生长激素(growth hormone,GH)是一种含有191个氨基酸的多肽类激素,分子质量为22 ku,由垂体前叶分泌进入血液循环,与靶细胞膜表面以二聚体形式存在的生长激素受体(growth hormone receptor,GHR)相结合。对于受体的激活来说,仅是二聚化还不够,还需在GH的诱导下发生构象变化,进而才能诱发Janus激酶2(Janus kinase 2,JAK2)的酪氨酸磷酸化,并通过4条不同的路径将信号传入细胞内,从而发挥代谢、增殖及分化等一系列生理效应。作者就生长激素与受体的结构、作用机理、信号转导通路的进展进行综述。     

不同泌乳相关激素和生长因子对奶牛乳腺上皮细胞增殖的影响

本研究旨在探讨不同泌乳相关激素和生长因子对奶牛乳腺上皮细胞增殖的影响及其与细胞外基质主要成分层黏连蛋白的关系。将正常的荷斯坦泌乳期奶牛乳腺上皮细胞进行体外培养,在未包被或包被层黏连蛋白的条件下,以MTT法检测催乳素(PRL)、牛生长激素(GH)、类胰岛素生长因子-1(IGF-Ⅰ)、类胰岛素生长因子-2(IGF-Ⅱ)对细胞增殖作用的影响。在层黏连蛋白包被条件下,进行血清恢复的同时添加不同泌乳相关激素和生长因子,GH、IGF-Ⅰ有促进细胞增殖的作用(P<0.05),PRL、IGF-Ⅱ有维持细胞存活的作用(P<0.05);无血清时,几种激素和生长因子单独添加均无明显促增殖效应(P>0.05)。无基质条件下,与血清联合使用时,PRL、GH、IGF-Ⅰ、IGF-Ⅱ均对细胞生长有不同程度促进作用(P<0.05);无血清时,仅IGF-Ⅰ使细胞增殖速率显著加快(P<0.05)。层黏连蛋白作为培养基质对于体外培养的泌乳乳腺上皮细胞生长速度没有显著促进作用,但有利于PRL和IGF-Ⅱ发挥促存活作用。PRL、GH、IGF-Ⅰ、IGF-Ⅱ对细胞增殖和存活有促进作用,但需要与血清中其他成分协同才能充分发挥作用,其中IGF-Ⅰ促增殖能力最强。     

Adrenergic regulation of growt hormone secretion in the ewe

This study examined the role of the adrenergic system in the regulation of growth hormone (GH) secretion in sheep. Intravenous infusion of noradrenaline (0.5μg/kg per min for 2 hr) totally suppressed plasma GH concentrations. Concomitant treatment of animals with the β-adrenergic antagonist propranolol completely blocked the noradrenaline-induced suppression of GH. In contrast, intravenous injection of the centrally acting α₂-agonist clonidine (2μg/kg) elicited a release of GH. To further investigate the central adrenergic regulation of GH secretion 10 μg of noradrenaline or adrenaline was microinjected (1μl) directly into the preoptic area of the hypothalamus of ovariectomized ewes. When the time of injection coincided with a GH trough period, both noradrenaline and adrenaline caused an increase in plasma GH concentrations, whereas if the injection coincided with an endogenous pulse of GH no additional GH response was obtained. In conclusion, these results provide evidence for the involvement of the adrenergic system in the regulation of GH secretion in sheep. Centrally, adrenergic pathways exert a stimulatory effect on GH release via an α₂-adrenergic system, whereas peripherally adrenergic pathways exert an inhibitory effect via β-adrenergic mediated mechanisms. Furthermore, adrenergic stimulation of the preoptic area may inhibit somatostatin activity and directly facilitate a GH pulse. Alternatively, adrenergic innervation of the preoptic area may influence neurons (somatostatin or other) that project to the arcuate nucleus and stimulate the release of GH-releasing factor.     

Low doses of estradiol partly inhibit release of GH in sheep without affecting basal levels

Estradiol increases basal growth hormone (GH) concentrations in sheep and cattle. This study sought to determine the effects of estradiol on GH-releasing hormone (GRH)-stimulated GH release in sheep. Growth hormone secretory characteristics, the GH response to GRH, and steady-state GH mRNA concentrations were determined in castrated male lambs treated with 2 different doses of estradiol 17-β for a 28-d experimental period. Although no differences between treatments in mean GH, basal GH, or GH pulse number were observed after 28 d of estradiol treatment, GH pulse amplitude was greater (P < 0.05) in the 2.00-cm implant-treated animals than in the control and 0.75-cm implant group. The effect of estradiol treatment on GRH-stimulated GH release revealed differences between the control and estradiol-treated animals (P < 0.05). The 15-min GH responses to 0.075 μg/kg hGRH in the control, 0.75-cm, and 2.00-cm implant groups, respectively, were 76 ± 10, 22.6 ± 2.1, and 43.6 ± 15.0 ng/mL. Growth hormone mRNA content was determined for pituitary glands from the different treatment groups, and no differences in steady-state GH mRNA levels were observed. There were no differences in the mean plasma concentrations of IGF-I, cortisol, T₃, or T₄ from weekly samples. Growth hormone release from cultured ovine pituitary cells from control sheep was not affected by estradiol after 72 h or in a subsequent 3-h incubation with estradiol combined with GRH. These data suggest that estradiol has differing actions on basal and GRH-stimulated GH concentrations in plasma, but the increase in pulse amplitude does not represent an increased pituitary sensitivity to GRH.     

Effects of growth hormone and gonadotrophin releasing hormone antagonists on ovarian follicle growth in sheep

Our objective was to determine the effects of the administration of growth hormone (GH) alone or plus teverelix, a gonadotrophin releasing hormone antagonist (GnRHa), on follicle development in sheep. Ewes were treated daily for 6 days by the intramuscular route with 15 mg of GH alone (GH group; n = 6) or combined with two subcutaneous doses of GnRHa (1.5 mg) on days 0 and 3 of GH treatment (GH/GnRHa group; n = 6); the control group (n = 6) received similar treatment with saline solution. Plasma follicle stimulating hormone levels were significantly lower in the GH/GnRHa group than in the control (P < 0.001) and GH groups (P < 0.05). The number of follicles > or =2 mm increased to reach significant differences with control (18.7 +/- 0.6) on day 4 in GH/GnRHa group (22.7 +/- 0.5, P < 0.001) and on day 5 in GH group (20.3 +/- 0.4 vs. 17.0 +/- 0.6, P < 0.05). These results indicate that GH and GnRHa may be useful for increasing the number of gonadotrophin-responsive follicles in the ovary. However, follicle function could be affected as both GH and GH/GnRHa groups showed lower plasma inhibin A concentrations than control sheep (90-110 pg/mL vs. 170-185 pg/mL, P < 0.005).     

Interactions of amino acids and hormones regulate the balance between growth and milk protein synthesis in lactating rats fed diets differing in protein content

Insulin-like growth factor-I (IGF-I), growth hormone (GH), and prolactin (PRL) play important roles in milk protein synthesis, and their plasma concentrations were reported to be affected by dietary protein intake. To investigate the relationship between circulating amino acid (AA) and concentrations of these hormones, 18 Wistar rats aged 14 wk were assigned to a low (LP; 9% protein), standard (SP; 21% protein), or high-protein (HP; 35% protein) diet from parturition through day 15 of lactation. Plasma, liver, pituitary gland, skeletal muscle, and mammary gland samples were collected at the end of treatment. Circulating and hepatic IGF-I concentrations increased linearly with elevated dietary protein concentrations (P < 0.0001). Rats receiving the HP diet had higher circulating GH (P < 0.01) and pituitary PRL concentrations (P < 0.0001) but lower pituitary GH concentration (P < 0.0001) relative to those in rats receiving the LP and SP diets. Pearson correlation test performed on composed data across treatments showed that several circulating AAs were correlated with circulating and tissue concentrations of IGF-I, GH, and PRL. Multiple linear regression analyses identified Leu, Gln, Ala, Gly, and Arg as the main AAs associated with hormone responses (R² = 0.37 ~ 0.80; P < 0.05). Rats fed the LP and HP diets had greater Igf1 and Ghr gene expression in skeletal muscle than those fed the SP diets (P < 0.01). However, LP treatment decreased Prlr mRNA abundance in mammary glands as compared with the SP and HP treatments (P < 0.05). The HP diets increased AA transporter expression (P < 0.01) but decreased mammalian target of rapamycin (P < 0.05) and 70 kDa ribosomal protein S6 kinase 1 (P < 0.01) phosphorylation in mammary glands as compared with the LP and SP diets. The results of the present study suggested that several circulating AAs mediated the effects of dietary protein supply on concentrations of IGF-I, GH, and PRL, which in turn altered the metabolism status in peripheral tissues including the lactating mammary glands.