Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During gestation, female rats become resistant to the anabolic actions of GH. The importance of this resistance for conceptus growth was investigated by treating pregnant dams on a reduced diet with ovine (o) or bovine (b) GH during days 10-20 of gestation. Reducing food intake to 60% that of ad libitum-fed controls significantly depleted maternal inguinal fat stores by day 20 of gestation, but it did not affect the growth of the fetuses or the placentas. In the food-restricted dams, twice daily injections of oGH (1 mg/day) or bGH (5 mg/day) during days 10-20 of gestation increased their inguinal fat pad wet weight by 28% and 62%, respectively, but had no effect on the wet weight of maternal heart, liver, or spleen. The dams treated with bGH had significantly heavier kidneys than the PBS- or oGH-treated females. On day 20 of gestation, control animals fed a 60%-diet had total serum insulin-like growth factor-I levels that were depressed to the same extent as those in ad libitum fed dams (i.e. to about 25% of the levels in nonpregnant females). Both the oGH and bGH treatments significantly elevated maternal serum insulin-like growth factor-I to 42% and 300%, respectively, of the levels in the untreated underfed dams. Compared to virgin controls, maternal tibial epiphyseal plate width was also significantly diminished in dams fed ad libitum or a 60% diet. Nevertheless, oGH and bGH were effective at augmenting maternal tibial epiphyseal plate width to equal those in virgin controls. Both doses of GH significantly reduced placental and fetal weights compared to those of PBS-injected dams on a 60% diet, and dams treated with the higher dose of GH were in an advanced stage of fetal and placental resorption by day 20 of gestation. Thus, maternal resistance to the anabolic actions of GH appears to be an important adaptation for diverting nutrients from the mother to the fetus.
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PMID:Administration of growth hormone to pregnant rats on a reduced diet inhibits growth of their fetuses. 193 82

Both insulin-like growth factor-I (IGF-I) and IGF-II have been shown to promote granulosa cell differentiation and proliferation. While both type I and type II IGF receptors have been observed in rat granulosa cells, the identity of the IGF receptor type(s) mediating IGF hormonal action remains uncertain. Whereas the role of the rat type I IGF receptor cannot be completely evaluated at this time due to the lack of specific reagents, the availability of antibodies specific for the rat type II IGF receptor (R-II-PAB1) has made studies of this receptor type possible. To validate the utility of the R-II-PAB1 antiserum at the level of the rat granulosa cell, its ability to immunoneutralize the granulosa cell type II IGF receptor was examined. Significantly, R-II-PAB1 (10-100 micrograms/ml) proved a potent inhibitor of [125I]IGF-II (but not [125I]IGF-I) binding to granulosa cell membrane preparations. Substantial, albeit finite, R-II-PAB1-mediated inhibition of the cross-linking of [125I]IGF-II was also observed. Moreover, R-II-PAB1 proved highly potent in immunoprecipitating the rat granulosa cell type II IGF receptor. In light of these observations, we have proceeded to use R-II-PAB1 to assess the functional role of the rat granulosa cell type II IGF receptor in IGF-I and IGF-II hormonal action. To this end, FSH (20 ng/ml)-primed granulosa cells were cultured for 72 h in the absence or presence of IGF-I or IGF-II (50 ng/ml) with or without increasing (receptor-active) concentrations of R-II-PAB1 (10-100 micrograms/ml). Control incubations were carried out with an ammonium sulfate precipitate of nonimmune rabbit serum dialyzed against PBS. Significantly, both R-II-PAB1 and nonimmune rabbit serum were without effect on the cytodifferentiative action of either IGF-I or IGF-II. Subject to limitations inherent to the immunoneutralizing potency of R-II-PAB1, these findings are in keeping with the notion that (inasmuch as the conventional cytodifferentiative process is concerned) the granulosa cell type II IGF receptor does not appear to participate in transmembrane IGF signalling. By inference, these findings also suggest that IGF-I and IGF-II hormonal action at the level of the granulosa cell may be exerted largely, if not exclusively, via the type I IGF receptor. Thus, the potential relevance and the functional role(s), if any, of the granulosa cell type II IGF receptor remain to be determined.
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PMID:Insulin-like growth factor-I (IGF-I) and IGF-II hormonal action in cultured rat granulosa cells: mediation via type I but not type II IGF receptors. 215 63

We have previously reported that pituitary vasoactive intestinal peptide (VIP) mediates through autoparacrine mechanisms insulin-like growth factor-I and TRH-stimulated PRL release. In the present study, we have investigated whether VIP might also be implicated in the PRL increase that follows dopamine (DA) withdrawal. The experiments were carried out in defined medium supplemented or not with T3, as in a previous study we had found that PRL release increases under low T3 culture conditions due to mediation by concomittant stimulus of VIP. Anterior pituitary (AP) cells from adult male rats were incubated for 1 h in the presence of DA (10 microM), a VIP-receptor antagonist (VIP-At) (200 nM), or DA plus VIP-At. Then media were removed and the cells were washed with PBS and reincubated under the same conditions but without the addition of DA. In the first incubation, DA inhibited PRL release by 80%, and VIP release by 20% in both T3-free and T3 medium. In the second period of incubation, PRL and VIP release were increased in AP cells previously exposed to DA. These effects were greater when the cells were cultured in T3-free medium than in T3-medium (225% and 150%, respectively for PRL release; and 155 and 135%, respectively for VIP release). PRL response to DA withdrawal was inhibited by the simultaneous presence of VIP-At. This inhibition was again greater when the cells were incubated in medium supplemented with T2. Thus, the stimulus of DA withdrawal was inhibited by 88% in T2-free medium and by 37% in T3-medium. To investigate whether pituitary VIP messenger RNA (mRNA) expression is under dopaminergic control, AP cells were incubated in the presence or absence of bromocriptine (BC) (10 nM) for 2 and 24 h. After 24 h of incubation, BC decreased mRNA levels of PRL and of the two transcripts which VIP expresses in AP. As with DA, BC also inhibited PRL and VIP release both at 2 and 24 h. These data demonstrate that VIP, at least partially, mediates DA withdrawal-induced PRL release through an autoparacrine action. They also suggest that simultaneous inhibition of pituitary VIP mRNA expression and VIP release may be a necessary mechanism for the dopaminergic inhibition of PRL mRNA expression and PRL release.
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PMID:Autoparacrine action of vasoactive intestinal peptide on dopaminergic control of prolactin secretion. 859 96

Transection of the sciatic nerve in neonatal rats results discernable loss of motor neurons in the spinal cord. This neuronal death could be due to lack of retrogradely transported target derived neurotrophic factors, since some of these factors have been shown to be effective in injury induced motor neuron death. Another hypothesis suggests that glutamate and its receptors has been implicated as possible mechanism for motor neuron death, because inhibitor of glutamate release and antagonists of glutamate receptors are effective in preventing axotomized motor neuron death. To investigate the effect of insulin-like growth factor-I (IGF-I) and riluzole, a drug that inhibits glutamate release, on axotomy induced motor neuron death. Newborn rats were anesthetized with hypothermia. Sciatic nerve was cut near the obturator tendon in the left thigh. Animals were then treated daily with different doses of IGF-I and riluzole for 14 days with intraperitoneal injections. Control rats received PBS in the same fashion. After the treatment, the number of surviving motor neurons and the motor neuron diameter in the L(4) was assessed. Both IGF-I (1.0 mg/kg) and riluzole (5.0 mg/kg) rescued motor neuron death in a similar way. Co-administration of IGF-I (1.0 mg/kg) and riluzole (5.0 mg/kg) was more effective than either agent alone and there was a statistically significant difference between co-administration and IGF-I alone. However there was no significant difference between simultaneous treatment and riluzole alone. As for diameter of motor neurons, riluzole (5.0 mg/kg) preserved the motor neuron diameter in the lesion side. Nonetheless, no further increase in motor neuron diameter was seen when riluzole (5 mg/kg) and IGF-I (1.0 mg/kg) were applied in combination. Both agents did not affect diameter of motor neurons in the non-axotomy side. Riluzole is available in amyotrophic lateral sclerosis (ALS) and the positive results of clinical trials with IGF-I suggests that combination treatment of IGF-I and riluzole in ALS remains to be determined.
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PMID:Prevention by insulin-like growth factor-I and riluzole in motor neuron death after neonatal axotomy. 1054 24

Pancreatic carcinoma cells overexpress the insulin-like growth factor-I (IGF-I) receptor (IGF-IR) and the hepatocyte growth factor (HGF) receptor, c-Met, which are both known to mediate tumor cell migration and invasion. We hypothesized that IGF-IR and c-Met cooperate to induce migration and invasion of human pancreatic carcinoma cells and that IGF-I-mediated migration and invasion depend on c-Met. Migration and invasion assays were done with the human pancreatic cancer cell line L3.6pl treated with PBS, IGF-I, HGF, or IGF-I plus HGF. To determine if c-Met is necessary for IGF-IR-mediated migration and invasion, c-Met was down-regulated in L3.6pl cells via adenoviral infection with a c-Met ribozyme before IGF-I treatment. IGF-I and HGF increased cell migration and invasion. Furthermore, IGF-I plus HGF had a greater than additive effect on cell migration and invasion compared with either growth factor alone. Down-regulation of c-Met nearly completely inhibited IGF-I-mediated migration and invasion. Our findings suggest that IGF-IR and c-Met cooperate to induce migration and invasion of human pancreatic carcinoma cells. Furthermore, c-Met is required for both HGF- and IGF-I-mediated migration and invasion. Elucidation of the signaling pathways that contribute to tumor progression and metastasis should provide a foundation for the development of targeted therapies for pancreatic carcinoma.
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PMID:Regulatory role of c-Met in insulin-like growth factor-I receptor-mediated migration and invasion of human pancreatic carcinoma cells. 1689 53