Endometrial expression of the insulin-like growth factor system during uterine involution in the postpartum dairy cow

Rapid uterine involution in the postpartum period of dairy cows is important to achieve a short interval to conception. Expression patterns for members of the insulin-like growth factor (IGF) family were determined by in situ hybridisation at day 14 ± 0.4 postpartum (n = 12 cows) to investigate a potential role for IGFs in modulating uterine involution. Expression in each uterine tissue region was measured as optical density units and data were analysed according to region and horn. IGF-I mRNA was localized to the sub-epithelial stroma (SES) of inter-caruncular and caruncular endometrium. Both IGF-II and IGF-1R expression was detected in the deep endometrial stroma (DES), the caruncular stroma and myometrium. IGFBP-2, IGFBP-4 and IGFBP-6 mRNAs were all localised to the SES of inter-caruncular and caruncular uterine tissue, and in the DES and caruncular stroma, with IGFBP-4 mRNA additionally expressed in myometrium. IGFBP-3 mRNA was only detectable in luminal epithelium. IGFBP-5 mRNA was found in myometrium, inter-caruncular and caruncular SES and caruncular stroma. These data support a role for IGF-I and IGF-II in the extensive tissue remodelling and repair which the postpartum uterus undergoes to return to its non-pregnant state. The differential expression of binding proteins between tissues (IGFBP-3 in epithelium, IGFBP-2, -4, -5 and -6 in stroma and IGFBP-4 and -5 in myometrium) suggest tight control of IGF activity within each compartment. Differential expression of many members of the IGF family between the significantly larger previously gravid horn and the previously non-gravid horn may relate to differences in their rate of tissue remodelling.     

Effects of L-carnitine on fetal growth and the IGF system in pigs

The effects of L-carnitine on porcine fetal growth traits and the IGF system were determined. Fourth-parity sows were fed a gestation diet with either a 50-g top dress containing 0 (control, n = 6) or 100 mg of L-carnitine (n = 6). At midgestation, fetuses were removed for growth measurements, and porcine embryonic myoblasts (PEM) were isolated from semitendinosus. Real-time quantitative PCR was used to measure growth factor messenger RNA (mRNA) levels in the uterus, placenta, muscle, hepatic tissue, and cultured PEM. A treatment x day interaction (P = 0.02) was observed for maternal circulating total carnitine. Sows fed L-carnitine had a greater (P = 0.01) concentration of total carnitine at d 57 than control sows. Circulating IGF-I was not affected (P = 0.55) by treatment. Supplementing sows with L-carnitine resulted in larger (P = 0.02) litters (15.5 vs. 10.8 fetuses) without affecting litter weight (P = 0.07; 1,449.6 vs. 989.4 g) or individual fetal weight (P = 0.88) compared with controls. No treatment effect was found for muscle IGF-I (P = 0.36), IGF-II (P = 0.51), IGFBP-3 (P = 0.70), or IGFBP-5 (P = 0.51) mRNA abundance. The abundance of IGF-I (P = 0.72), IGF-II (P = 0.34), and IGFBP-3 (P = 0.99) in hepatic tissue was not influenced by treatment. Uterine IGF-I (P = 0.46), IGF-II (P = 0.40), IGFBP-3 (P = 0.29), and IGFBP-5 (P = 0.35) mRNA abundance did not differ between treatments. Placental IGF-I (P = 0.30), IGF-II (P = 0.18), IGFBP-3 (P = 0.94), and IGFBP-5 (P = 0.42) mRNA abundance did not differ between treatments. There was an effect of side of the uterus for IGF-I (P = 0.04) and IGF-II (P = 0.007) mRNA abundance; IGF-I mRNA abundance was greater in the left uterine horn than in the right uterine horn (0.14 and 0.07 relative units, respectively). Placental IGF-II mRNA abundance was greater (P = 0.007) in the left than in the right uterine horn (483.5 and 219.59, respectively). The abundance of IGFBP-3 was not affected by uterine horns in either uterine (P = 0.66) or placental (P = 0.13) tissue. There was no treatment difference for IGF-I (P = 0.31) or IGFBP-5 (P = 0.13) in PEM. The PEM isolated from sows fed L-carnitine had decreased IGF-II (P = 0.02), IGFBP-3 (P = 0.03), and myogenin (P = 0.04; 61, 59, and 67%, respectively) mRNA abundance compared with controls. These data suggest that L-carnitine supplemented to gestating sows altered the IGF system and may affect fetal growth and development.     

Follicular Dominance in Cattle Is Associated With Divergent Patterns of Ovarian Gene Expression for Insulin-Like Growth Factor (IGF)-I,IGF-II,and IGF Binding Protein-2 in Dominant and Subordinate Follicles

A decrease in insulin-like growth factor (IGF) binding protein (BP) amount occurs within the follicular fluid of dominant ovarian follicles. At the same time, concentrations of follicular fluid IGF-I do not change. The mRNA for IGF-I, IGF-II, IGFBP-2, and IGFBP-3 in dominant and subordinate follicles were measured to determine if changes in IGF or IGFBP gene expression are associated with follicular dominance. Heifers were ovariectomized during a follicular wave, either during early-dominance (emerging dominant follicle, 9 mm diameter) or mid-dominance (established dominant follicle, 14–16 mm diameter). Follicles were classified as either dominant (DF), subordinate (SF), or not-recruited (NRF; small antral follicles). mRNA was localized by in situ hybridization and measured by image analyses. The IGF-I mRNA (granulosa cells) was greatest in DF and increased in DF, SF, and NRF from early- to mid-dominance. Likewise, IGF-II mRNA (theca cells) was greatest in DF compared with SF or NRF. The IGFBP-2 mRNA (granulosa cells), however, was nearly undetectable in DF, whereas adjacent SF expressed abundant IGFBP-2 mRNA. The NRF were not uniform in their IGFBP-2 expression because only 5 of 13 NRF had IGFBP-2 mRNA. The IGFBP-3 mRNA (granulosa cells) was found only in two NRF, suggesting that local synthesis is not a predominant source of follicular fluid IGFBP-3. These data show that changes in gene expression for IGFBP-2 are opposite to those for IGF-I or IGF-II. Increased IGF-I and IGF-II mRNA and decreased IGFBP-2 mRNA within the DF may be one mechanism leading to follicular dominance. The opposite pattern of IGFBP-2 gene expression in SF and some NRF may lead to follicular atresia.     

Changes in the local regulation of insulin-like growth factors I and II and insulin-like growth factor-binding proteins in osteoarthritis of the canine stifle joint secondary to cruciate ligament rupture

OBJECTIVES: To investigate changes in concentrations of insulin-like growth factors I (IGF-I) and II (IGF-II) and the expression of IGF-binding proteins (IGFBP) in synovial fluids from dogs with naturally occurring osteoarthritis (OA) of the canine stifle joint secondary to cranial cruciate ligament (CCL) rupture. STUDY DESIGN: Prospective study with synovial fluid sampling from diseased and contralateral unaffected joints at 0, 1.5, and 5 months. SAMPLE POPULATION: Eleven dogs with unilateral CCL deficiency, with unaffected contralateral joints. METHODS: IGF-I and IGF-II concentrations in synovial fluids were estimated by radioimmunoassay at 0, 1.5, and 5 months; Western ligand blotting was performed for intact IGFBPs at 0, 1.5, 5, and 9 months. Both stifle joints were radiographed at 0, 7, and 13 months. RESULTS: The IGF system is altered after CCL rupture and during development of early OA. Mean IGF-I and IGF-II concentrations in index stifle joints at study entry were 201.6 microg/mL and 345.7 microg/mL, respectively, compared with 57.7 microg/mL and 79.4 microg/mL, respectively, for contralateral joints. Index joint IGF concentrations increased after surgical treatment and then declined, although they remained higher than contralateral joints. Index joints had increases in IGFBP-3 and -4, and a decrease in IGFBP-2 expression compared with contralateral joints. CONCLUSIONS: Although IGF concentrations are increased in canine OA, alterations in IGFBP profiles may limit the tissue availability of IGF. CLINICAL RELEVANCE: Manipulation of the IGF system may provide an opportunity for novel treatments of OA in dogs.     

Ontogenic maturation of the somatotropin/insulin-like growth factor axis

The ontogeny of the somatotropin/insulin-like growth factor system was examined in well-fed pigs under basal conditions and during a short-term challenge of porcine ST (pST). The study was conducted with two replicates of eight castrate male pigs from 3.8 kg BW (10 d of age) to 92 kg BW (129 d of age). Pigs were reared individually with ad libitum access to milk replacer through 23 d of age. Thereafter, pigs were fed a corn, soybean meal, and dry skim milk diet formulated to exceed nutrient requirements by approximately 30%. Pigs were randomly assigned to receive daily i.m. injections of either 0 (buffer) or 120 microg/kg BW of pST for a duration of 4 d starting at 10, 19, 33, 43, 63, 83, and 125 d of age. Blood was collected via jugular venipuncture on d 0 and 4 of the challenge. Circulating levels of IGF-I were not dramatically affected by age, but levels of IGF-II were low from 10 to 19 d of age and then increased through later stages of growth. Circulating concentrations of IGF binding protein (BP)-3 increased with age (P < .05), but levels of IGFBP-2, a 30-kDa IGFBP, and IGFBP-4 were unchanged (P > .10). The pST challenge reduced plasma urea nitrogen at all ages, but the magnitude of the response was less in younger pigs compared with the maximum response in pigs greater than 30 kg BW (63 d of age). The IGF-I response to the pST challenge also increased from approximately 30% in young pigs to a threefold increase in older pigs. Regardless of age, concentrations of IGF-II were minimally affected by the pST challenge. Circulating levels of IGFBP-3 increased and IGFBP-2 levels decreased in response to the pST challenge, and the magnitude increased with age. The high nutritional status of pigs in the early phases of growth diminished the postnatal changes in IGF-I and IGFBP-2, but not IGF-II or IGFBP-3. Overall, data demonstrate a developmental regulation of the ST/IGF system, with pST challenges altering circulating concentrations of IGF-I, IGFBP-3, and IGFBP-2 coincident with changes in amino acid metabolism.     

Expression of matrix metalloproteinases during vascularization and ossification of normal and impaired avian growth plate

Enzymes of the matrix metalloproteinase (MMP) family regulate angiogenesis and are involved in the endochondral ossification process. Tibial dyschondroplasia (TD) and rickets are 2 disorders associated with impairments in this process, mainly in the vascularization of the avian growth plate. In this paper, we induced TD and rickets and studied the expression patterns of 4 members of the MMP family known to be important for endochondral ossification, MMP-2, 3, 9, and 13, in normal and impaired avian growth plates. The expression of MMP-3, 9, and 13 was reduced in the lesions and lined up parallel to the expulsion of blood vessels, which was extended up to the border of the lesion, but did not penetrate into it. Matrix metallopro-teinase-2 was not expressed in the TD lesion but was overexpressed in the rachitic lesion. We also studied the differentiation stage of the chondrocytes populating the lesions and found that the rachitic lesions were populated with proliferative chondrocytes, whereas the TD lesions were filled with chondrocytes that presented both proliferative and hypertrophic markers. These results suggest that MMP-3, 9, and 13 play a role in the vascularization and ossification processes, whereas MMP-2 is related to chondrocyte differentiation and may be involved in cartilage remodeling in the avian growth plate.     

Immunohistochemical detection of components of the insulin-like growth factor system during skeletal muscle growth in the pig

The insulin-like growth factor (IGF) system plays an important role in postnatal somatic and skeletal muscle growth in pigs. There is little information on the occurrence and distribution of components of the IGF system in postnatal porcine skeletal muscle. IGF-I, IGF receptor 1 (IGF1R) and the IGF-binding proteins IGFBP-1 and -3 in longissimus dorsi and triceps brachii were localized in muscle biopsies from 12 commercially crossbred pigs aged from 28 to 199 days as well as from the sire generation, by immunohistochemistry. Plasma IGF-I concentrations were also determined using radio-immunoassays. Unlike other species, IGF-I was localized in porcine skeletal muscle fibres. Staining intensity correlated with the highest plasma IGF-I levels and phases of intensive muscle growth from the 11th to 22nd week. The pattern of IGF1R immunostaining, which was strong, correlated with that of IGF-I, IGF1R was also localized in endomysial tissues. IGFBP-1 was not detected within muscle fibres, but was found in the endomysium and vessel walls, while IGFBP-3 was localized with IGF-1 and its receptor. Higher magnification revealed that IGF1R, IGFBP-3 and probably IGF-I appeared in the tubular system. Inhibitory as well as stimulating controls of IGFBP-1 and -3 on IGF functions are discussed, which may maintain a balance between autocrine growth promoting activities of IGF-I and IGF1R.     

Effects of colostrum feeding and dexamethasone treatment on mRNA levels of insulin-like growth factors (IGF)-I and -II, IGF binding proteins-2 and -3, and on receptors for growth hormone, IGF-I, IGF-II, and insulin in the gastrointestinal tract of neonatal calves

The somatotropic axis regulates growth of the gastrointestinal tract (GIT). In addition, colostrum feeding and glucocorticoids affect maturation of the GIT around birth in mammals. We have measured mRNA levels of members of the somatotropic axis to test the hypothesis that colostrum intake and dexamethasone treatment affect respective gene expression in the GIT. Calves were fed either colostrum or an isoenergetic milk-based formula, and in each feeding group, half of the calves were treated with dexamethasone (DEXA; 30 microg/kg body weight per day). Individual parameters of the somatotropic axis differed (P < 0.05) among different GIT sections and formula feeding increased (P < 0.05) mRNA levels of individual parameters at various sites of the GIT. Effects of DEXA on the somatotropic axis in the GIT partly depended on different feeding. In colostrum-fed calves, DEXA decreased (P < 0.05) mRNA levels of IGF-I (esophagus, fundus, duodenum, and ileum), IGF-II (fundus), IGFBP-2 (fundus), IGFBP-3 (fundus), IGF1R (esophagus, ileum, and colon), IGF2R (fundus), GHR (fundus), and InsR (esophagus, fundus), but in formula-fed calves DEXA increased mRNA levels of IGF-I (esophagus, rumen, jejunum, and colon). Furthermore, DEXA increased (P < 0.05) mRNA levels of IGF-II (pylorus), IGFBP-3 (duodenum), IGF2R (pylorus), and GHR (ileum), but decreased mRNA levels of IGFBP-2 (ileum), and IGF1R (fundus). Whereas formula feeding had stimulating effects, effects of DEXA treatment on the gene expression of parameters of the somatotropic axis varied among GIT sites and partly depended on feeding.     

The relationship between endogenous insulin-like growth factors and growth in pigs.

Previous studies have reported conflicting data on gender differences in plasma IGF-I in postnatal pigs. There is also debate over the role of IGF-II in regulation of postnatal growth. We have, therefore, determined the concentrations of plasma IGF-I, IGF-II, and IGF-binding protein-3 (IGFBP-3) in boars, barrows, and gilts and related these to postnatal growth characteristics. Plasma concentrations of IGF-I were higher in boars than in gilts or barrows from 13 wk. of age, and plasma IGF-II levels were generally higher in barrows than in boars or gilts. Plasma IGFBP-3 levels were higher in boars than in gilts or barrows at most ages. Between 15 and 23 wk. of age, IGF-I and IGFBP-3, but not IGF-II, were positively associated with growth rate, voluntary feed intake, and gain:feed ratio. Plasma IGF-II, but not IGF-I or IGFBP-3, was positively associated with backfat depth during this period. These results support the hypothesis that circulating IGF-I and IGF-II are regulators of lean and adipose tissue growth, respectively.     

Effects of fasting on IGF-I,IGF-II,and IGF-binding protein mRNA concentrations in channel catfish (Ictalurus punctatus)

The effects of fasting on insulin-like growth factor (IGF)-I, IGF-II, and IGF-binding protein (IGFBPs) mRNA in channel catfish were examined. Fed control fish (Fed) were compared to fish that had been fasted for 30 d followed by 15 d of additional feeding (Restricted). Sequence alignment and similarity to orthologous proteins in other vertebrates provided structural evidence that the 3 catfish sequences identified in the present research were IGFBP-1, -2, and -3. Prolonged fasting (30 d) reduced body weight approximately 60% (P < 0.001) and decreased IGF-I mRNA in the liver and muscle (P < 0.01). Fifteen days of re-feeding restored concentrations of hepatic and muscle IGF-I mRNA. Liver IGF-II mRNA was not affected by fasting but was increased 2.2-fold after 15 d of re-feeding (P < 0.05). Abundance of muscle IGF-II mRNA was similar between the fed control group and the restricted group throughout the experimental period. Fasting also increased liver IGFBP-1 mRNA (P < 0.05) and decreased IGFBP-3 mRNA (P < 0.01), whereas abundance of IGFBP-2 mRNA was not significantly affected. Interestingly, re-feeding for 15 d did not restore concentrations of IGFBP-1 and IGFBP-3 mRNA relative to fed control concentrations. The IGF results suggest that IGF-I and IGF-II are differently regulated by nutritional status and probably have a differential effect in promoting muscle growth during recovery from fasting. Similar to mammals, IGFBP-1 mRNA in catfish is increased during catabolism, whereas IGFBP-3 mRNA is decreased during inhibited somatic growth. The IGFBP results provide additional evidence of the conserved nature of the IGF-IGFBP-growth axis in catfish.     

Exogenous somatotropin alters IGF axis in porcine endometrium and placenta

The aim of this study was to examine whether exogenous somatotropin (ST) can alter the insulin-like growth factor (IGF) axis in the porcine epitheliochorial placenta. Crossbred gilts were injected either 6 mg of recombinant porcine ST or vehicle from days 10 to 27 after artificial insemination (term day 116). Control and ST-treated gilts were euthanized on day 28 (8 control/5 treated), day 37 (4 control/6 treated), and day 62 (4 control/6 treated) of gestation. Endometrium and placental tissue samples were collected and subjected to mRNA analyses. In control gilts, somatotropin receptor (STR) and IGF-I mRNA abundance in the endometrium decreased with gestation. Conversely, the amounts of IGF-II mRNA and of IGF binding protein (BP)-2 and -3 mRNA, which were analyzed in endometrium and placental chorion, increased with gestation. The endometrium contained less IGF-II mRNA but more IGFBP-2 and-3 mRNA than the placental chorion. In response to pST treatment, the amounts of endometrial STR and IGF-I mRNA were lower at days 28 and 37, but higher at day 62 of gestation. The content of IGF-II mRNA was higher in the endometrium of pST-treated than control gilts on day 37. The amount of IGFBP-2 mRNA was increased on day 37 in endometrium and placenta of pST-treated gilts, whereas no changes in IGFBP-3 mRNA were observed. The IGF-II/IGFBP-2 ratio was higher in the placenta in response to pST on day 28 of gestation. Results show that pST treatment of pregnant gilts during early gestation alters IGF axis in maternal and fetal placental tissues and suggest pST may exert an effect on fetal growth by altering the relative amount of IGFBPs and IGFs at the fetal-maternal interface.     

Alteration of the gene and protein levels of insulin-like growth factors in streptozotocin-induced diabetic male rats

Insulin-like growth factor (IGFs: IGF-I and IGF-II) systems have been reported to be associated with the onset of diabetic mellitus. Therefore, we investigated the effect of diabetes on regulation of the IGF system in the liver, kidneys and heart, which are important organs in the pathogenesis of diabetes. The experimental groups were subdivided into three groups: 1) controls, 2) streptozotocin (STZ)-induced untreated diabetic group, and 3) an insulin-treated group (plus diabetic rats). In the present study, starting on the second day after STZ treatment, the diabetic group exhibited hyperglycemia, polyuria, and polydipsia, which are characteristic of diabetes melittus. Serum levels of IGF-I were decreased, but those of IGF-II were increased in the diabetic group compared with the controls. The expression levels of IGF-I and IGF-II protein in the livers of the diabetic group had a similar pattern to the serum. In addition, the expression levels of liver IGF-I mRNA and IGF-II mRNA were decreased in the diabetic groups. In the heart, IGF-I levels were decreased, but IGF-II levels were increased in the untreated diabetic groups, which was consistent with the expression levels of their mRNA. However, both the IGF-I and IGF-II levels in the kidneys were increased in the untreated diabetic groups, but the mRNA levels were decreased. Insulin treatment ameliorated the changes of IGF system in the serum, liver, kidneys, and heart. In conclusion, diabetes induced alteration of the IGF system tissue-specifically, and this was blocked by insulin treatment.     

Moderate doses of porcine somatotropin do not increase plasma insulin-like growth factor-I (IGF-I) or IGF binding protein-3.

The growth rate of the young pig is generally much less than its potential and may be constrained by endocrine status as well as by nutrient intake. The aim of this study was to determine whether porcine somatotropin (pST) could increase growth in the nursing pig. Fourteen sows nursing litters of 6 (n = 7) or 12 (n = 7) piglets were utilized to establish a high and low plane of nutrition for sucking pigs. On Day 4 of lactation, the median two male pigs from each litter were randomly allocated to one of two doses of pST (0 or 60 micrograms/kg/d) until weaning on Day 31. Pigs were bled on Days 4, 13, 22, and 31 of lactation and the plasma was analyzed for insulin-like growth factor (IGF)-I, IGF-II, and IGF binding protein-3 (IGFBP-3). Pigs were weaned into conventional accommodation and further weighed on Days 63, 91, and 119. Pigs from litters of 6 grew more quickly and weighed 2.2 kg (P = 0.01) and 3.5 kg (P = 0.04) more than pigs from litters of 12 at 31 and 63 d of age, respectively. There was no effect of pST on preweaning growth of sucking pigs (261 vs. 258 g/d, P = 0.68), although growth rate increased in the final 3 d before weaning at 31 d (241 vs. 294 g/d, P = 0.01). IGFBP-3 was greater (1.09 vs. 0.78 micrograms/ml, P < 0.001), whereas IGF-I tended to be greater (206 vs. 176 ng/ml, P = 0.14), in pigs from the small litters. There was no effect of pST on plasma IGF-I (182 vs. 195 ng/ml, P = 0.454) or IGFBP-3 (0.93 vs. 0.94 microgram/ml, P = 0.85) concentrations. Plasma IGF-I and IGFBP-3 were highly correlated with the growth rate of nursing pigs (R = 0.638 and 0.756, respectively). There were no effects of pST (340 vs. 328 ng/ml, P = 0.48) or litter size (336 vs. 333 ng/ml, P = 0.88) on IGF-II. In conclusion, pST had no little or no effect on growth performance or plasma IGF-I, IGF-II, or IGFBP-3 in sucking pigs on either a high or low plane of nutrition.     

Nutritional regulation of the genes encoding the acid-labile subunit and other components of the circulating insulin-like growth factor system in the sheep

In sheep, perinatal maturation of the endocrine arm of the insulin-like growth factor (IGF) system is characterized by two developmental events. First, concentrations of circulating IGF-I increase rapidly after birth and become responsive to changes in nutrition and growth hormone (GH). Second, the liver initiates synthesis of a serum protein called the acidlabile subunit (ALS). The acid-labile subunit promotes the endocrine actions of IGF-I and -II by recruiting them to long-lived complexes of 150 kDa. In this study, we examined the effect of nutrition on hepatic expression of the ALS gene around the time of birth and later in life. Expression of genes encoding other components of the circulating IGF system was also measured. At d 130 of fetal life, fetuses suffering from chronic undernutrition caused by placental insufficiency had lower expression of the ALS and IGF-I genes than well-nourished fetuses, but they did not have any changes in the expression of the IGF-binding protein (IGFBP)-2 or IGFBP-3 genes. In early postnatal life, hepatic gene expression was analyzed between d 12 and 38 in lambs fed a milk replacer at levels sustaining weight gains of 150 or 337 g/d. The lower plane of nutrition decreased the expression of the ALS, IGF-I, and GH receptor genes and increased the expression of the IGFBP-2 gene; expression of the IGFBP-3 gene was not affected by nutrition at this stage of life. Finally, hepatic gene expression was measured in 3-mo-old lambs offered ad libitum levels of a balanced diet or of a diet limiting for both energy and protein. Although the rate of growth of the lambs fed the limiting diet was reduced by 38%, the only effect detected in hepatic gene expression was a ninefold increase in the abundance of IGFBP-2 mRNA. Overall, these results indicate that undernutrition during late fetal and early postnatal life delays hepatic expression of the ALS gene and final maturation of the endocrine IGF system.     

Genetic models for the study of insulin-like growth factors (IGF) and muscle development in birds compared to mammals.

IGFs are important positive modulators of overall body and muscle growth in different species. Genetic variation in IGF-I gene expression exists as shown by the possibility of genetic selection for high or low circulating IGF-I concentrations in mice and the associated variations in growth potential. Targeted over-expression of IGF-I in transgenic mice results in muscle hypertrophy, but it is yet unknown whether genetic variability in muscle IGF-I gene expression exists. Much less data are available in birds. This review is focussed on the potential role of IGFs on chicken muscle development. Apart from the absence of a type 2 IGF receptor (IGF-II receptor), the general characteristics of the chicken IGF system seem to be similar to mammalian species. In different genetic models with altered growth rates or body composition, differences in the IGF system are observed suggesting its importance in regulating body growth in those species. The components for a paracrine action of IGF are also present in chicken muscle but it has not yet been demonstrated if they contribute to differences in muscle development.     

Growth hormone suppresses the expression of IGFBP-5, and promotes the IGF-I-induced phosphorylation of Akt in bovine mammary epithelial cells

Growth hormone (GH) plays a specific role to inhibit apoptosis in the bovine mammary gland through the insulin-like growth factor (IGF)-I system, however, the mechanism of GH action is poorly understood. In this study, we show that GH dramatically inhibits the expression of IGFBP-5, and GH along with IGF-I enhanced the phosphorylation of Akt through the reduction of IGF binding protein (IGFBP)-5. To determine how GH affects Akt through IGF-I in bovine mammary epithelial cells (BMECs), we examined the phosphorylation of Akt in GH treated BMECs and found that IGF-I induced phosphorylation of Akt was significantly enhanced by the treatment with GH. We demonstrated that GH reduces mRNA and protein expression of IGFBP-5 in BMECs, but it does not affect the expression of IGFBP-3. To determine that the enhanced effect of the Akt phosphorylation by the treatment of GH is due to the inhibition of the expression of IGFBP-5, we examined the effect of IGFBP-3 and -5 on the phosphorylation of Akt through IGF-I in the GH-treated BMECs. The phosphorylation of Akt was inhibited in a dose-dependent manner when IGFBP-5 was added at varying concentrations and was also inhibited in the presence of IGFBP-3. The results of this study suggest that GH plays an important role on mammary gland involution in bovine mammary epithelial cells.