Developmental regulation of insulin-like growth factor-I and growth hormone receptor gene expression

Shoba, Lungile N. N.; An, Mi Ra; Frank, Stuart J.; Lowe, William L.

doi:10.1016/s0303-7207(99)00045-3

Cited by 46 publications

(22 citation statements)

References 53 publications

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“…There have been two fetal versus postnatal liver analyses of JAK/STATs in the rat (Shoba et al 1999, Phornphutkul et al 2000. Contrary to our data (Goodyer et al 2001a), Phornphutkul et al (2000) found no difference in GH binding levels between late gestation (d17, d19) fetal and postnatal rat livers.…”

Section: Discussioncontrasting

confidence: 99%

“…Finally, GH was able to enhance CATexpression of two GHRE reporter vectors transfected into FHs, leading Phornphutkul et al (2000) to conclude that hepatic GH signaling mechanisms are functional in the late gestation rat. Similar to our data (Goodyer et al 2001a), Shoba et al (1999) found a marked increase in GHR mRNA and protein in fetal (d17) compared with postnatal (4 months) rat livers. Over the same time frame, surprisingly, JAK2, STAT1, and STAT3 protein levels dropped while STAT5 levels remained unchanged.…”

Section: Discussionsupporting

confidence: 93%

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Developmental changes in the human GH receptor and its signal transduction pathways

Kenth

Mergelas²,

Goodyer

2008

Journal of Endocrinology

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We previously reported the presence of functional human GH receptors (hGHRs) in the human fetal hepatocyte (FH) as early as the first trimester. Interestingly, fetal serum levels of hGH are in the acromegalic range, yet certain hGH-dependent factors are expressed at very low levels (IGF-I, IGF-binding protein-3), suggesting that fetal liver has limited responsiveness to hGH. To determine whether this is due to the fetal tissue levels of hGHR or factors in the hGH/hGHR axis that might influence hGHR function, we compared hGHR isoforms and downstream signaling proteins in FH versus human adult liver (HAL). Immunoprecipitation/immunoblotting (IB) analyses found similar precursor and mature hGHR forms while RT-PCR assays of truncated (T) hGHR 1-279 , dominant negative for the full-length (FL) receptor, showed similar T/FL mRNA ratios in FH and HAL. IB demonstrated that Janus kinase (JAK) 2, signal transducers and activators of transcription (STAT(1, 3, 5A/B)), and suppressors of cytokine signaling (SOCS(1, 2, 3, cytokineinducible SH2-containing protein (CIS))) proteins were detectable in all FH and HAL tested (12 weeks of fetal age to 60 years); the levels were similar (STAT5B) or lower (JAK2/STAT1/STAT3/STAT5A: 38-53%, SOCS/CIS: 58-76%) in FH compared with HAL. Our studies to date demonstrate that, during hepatocyte development, hGHR levels are lower in the fetal cells but the hGHR isoforms, including the relative amount of truncated versus FL, remain unchanged. The JAK2/STAT/SOCS signaling molecules are present in the FH as early as the first trimester. However, they are generally at !50% level in postnatal liver. These data suggest that low expression of both hGHR and major hGHR signaling components may explain the limited responsiveness of the fetal cells to the high circulating levels of hGH.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 93%

Developmental changes in the human GH receptor and its signal transduction pathways

Kenth

Mergelas²,

Goodyer

2008

Journal of Endocrinology

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“…Moreover, these authors showed that GH stimulation of the receptor-induced tyrosine kinase activity, indicating that the fetal rat lung GHR is functional. Shoba et al (1999) similarly correlated GHR abundance in the rat lung with the activity of proteins involved in GHR signaling (STAT-1, -3, -5, and JAK 2), and Lu et al (2001) found that a GHregulated gene (Grtp1) was also present in the rat lung. The presence of GH and GHR in the developing lungs of perinatal and neonatal rats, therefore, suggests GH actions in lung development or in pulmonary function.…”

Section: Discussionmentioning

confidence: 84%

Growth hormone expression in the perinatal and postnatal rat lung

Beyea

Olson

Harvey

2005

Developmental Dynamics

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It is now established that the lung is a target site for pituitary growth hormone (GH) action, because pathophysiological states of pituitary GH excess and deficiency are associated with impaired pulmonary function. The onset of lung development and differentiation is, however, before the ontogenic differentiation of pituitary somatotrophs. GH may be involved, nevertheless, in lung development, because it is present in extrapituitary tissues of preimplantation mouse embryos and in the lung buds of embryonic chickens. The possibility that GH may be expressed in the rat lung during fetal and neonatal development, therefore, has been assessed. GH mRNA was detected in the lung, and its 693-bp sequence was identical to that in the pituitary gland. By in situ hybridization, this transcript was found to be abundantly expressed in the lungs of embryonic day (ED) 17 rats in mesenchymal, mucosal epithelial, and smooth muscle cells. This transcript was expressed in neonates until at least day 14 postnatally and was localized to type I and II epithelial cells and to pulmonary tissue macrophages and alveolar macrophages. GH immunoreactivity paralleled GH mRNA cellular localization throughout the time course studied. This immunoreactivity was specific and was lost after antibody preabsorption. The perinatal and postnatal lung is, therefore, an extrapituitary site of GH gene expression during development. Given that the GH receptor is present in the lung from early development, lung GH may have autocrine and/or paracrine roles in lung growth or differentiation or in pulmonary function.

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“…In the brain, IGF-I is expressed mainly by neurons, especially those in the relay centers of the somatosensory and cerebellar systems (34). GH produced in the brain may influence neuronal IGF-I production, as levels of GH receptor mRNA coordinate with those of IGF-I mRNA (38). In addition, neuronal IGF-I expression is influenced by developmental stage (34), nutrition status (39), glucocorticoid (40), and brain injury (18,41).…”

mentioning

confidence: 99%

Potential Role of IGF-I in Hypoxia Tolerance Using a Rat Hypoxic-Ischemic Model: Activation of Hypoxia-Inducible Factor 1α

et al. 2004

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Hypoxia preconditioning and subsequent tolerance to hypoxia-ischemia damage is a well-known phenomenon and has significant implications in clinical medicine. In this investigation, we tested the hypothesis that the transcriptional activation of IGF-I is one of the underlying mechanisms for hypoxia-induced neuroprotection. In a rodent model of hypoxia-ischemia, hypoxia preconditioning improved neuronal survival as demonstrated by decreased hypoxia-ischemia-induced neuronal apoptosis. To study the role of IGF-I in hypoxia tolerance, we used in situ hybridization to examine IGF-I mRNA distribution on adjacent tissue sections. In cerebral cortex and hippocampus, hypoxia preconditioning resulted in an increase in neuronal IGF-I mRNA levels with or without hypoxia-ischemia. To test its direct effects, we added IGF-I to primary neuronal culture under varying oxygen concentrations. As oxygen concentration decreased, neuronal survival also decreased, which could be reversed by IGF-I, especially at the lowest oxygen concentration. Interestingly, IGF-I treatment resulted in an activation of hypoxia-inducible factor 1␣ (HIF-1␣), a master transcription factor for hypoxiainduced metabolic adaptation. To evaluate whether IGF-I transcriptional activation correlates with HIF-1␣ activity, we studied the time course of HIF-1␣ DNA binding activity in the same rat model of hypoxia-ischemia. After hypoxia-ischemia, there was an increase in HIF-1␣ DNA binding activity in cortical tissues, with the highest increase around 24 h. Like IGF-I mRNA levels, hypoxia preconditioning increased HIF-1␣ DNA binding activity alone or with subsequent hypoxia ischemia. Overall, our results suggest that IGF-I transcriptional activation is one of the metabolic adaptive responses to hypoxia, which is likely mediated by a direct activation of HIF-1␣. Abbreviations HIF-1, hypoxia-inducible factor 1 HIF-1␣, hypoxia-inducible factor 1␣ HIF-1␤, hypoxia-inducible factor 1␤ VEGF, vascular endothelial growth factor dNTP, nucleotides dGTP, 2'-deoxyguanosine 5'-triphosphate, sodium salt dCTP, 2'-deoxycytidine 5'-triphosphate, sodium salt dTTP, 2'-deoxythymidine 5'-triphosphate, sodium salt dATP, 2'-deoxyadenosine 5'-triphosphate, sodium salt SSC, sodium chloride and sodium citrate buffer EMSA, electrophoretic mobility shift assay W18, wild-type M18, mutant MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide ϩϩϩ ] RT-PCR, reverse transcription PCR Hypoxia preconditioning is a process by which prior treatment of a sublethal dose of hypoxia renders cells tolerant to otherwise lethal hypoxia or hypoxia/ischemia insult. This phenomenon has been observed at cellular (1), tissue (2), and whole animal levels (3-6). Preconditioning and subsequent tolerance is not unique to hypoxia. In the brain, neurons can become tolerant to ischemia if exposed to a brief sublethal episode of ischemia (7,8), spreading depression (9), or exposure to metabolic inhibitors (10). To survive, cells seem to be armed with sophisticated adaptive mechanisms that enable them to sense t...

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Developmental regulation of insulin-like growth factor-I and growth hormone receptor gene expression

Cited by 46 publications

References 53 publications

Developmental changes in the human GH receptor and its signal transduction pathways

Developmental changes in the human GH receptor and its signal transduction pathways

Growth hormone expression in the perinatal and postnatal rat lung

Potential Role of IGF-I in Hypoxia Tolerance Using a Rat Hypoxic-Ischemic Model: Activation of Hypoxia-Inducible Factor 1α

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