Skip to main content
SpringerLink
Log in

Analysis of Growth Hormone Effects on Hepatic Gene Expression in Hypophysectomized Rats

  • Chapter
Genomics in Endocrinology

Part of the book series: Contemporary Endocrinology ((COE))

  • 891 Accesses

Abstract

As indicated by its name, the Growth hormone is the main regulator of longitudinal growth in mammals. GH is mainly produced in the pituitary gland and acts distantly on target tissues through the activation of the transmembrane GH receptor. The liver expresses the highest content of GH receptor. Accordingly, the liver is of key importance for the physiological actions of GH. Global expression analysis of the hepatic GH actions using microarrays clearly indicate that most of the known physiological effects of GH can be explained, at least in part, through its effects on the transcription of specific genes. To this end, GH is known to activate a network of transcription factors in liver that include among others the nuclear receptor such as PPARα, CAR or SHP, buts also SREBP CRBP, and STAT5b. The latest is of particular importance in the regulation of body growth through its regulation of the expression of IGF-I and the ALS of the IGFBP3 binding protein which in turn mediate many of the GH actions in extra hepatic tissues. STAT5b and presumably the members of the nuclear receptor family under GH control also influence genes involve in xenobiotic metabolism. GH actions in liver lead to increase lipogenesis and decreased aminoacid catabolism, thereby promoting anabolic growth in bone and muscle tissue. These effects can be explained by increase expression of lipogeneic genes as consequence of the activation of the key lipogenic transcription factor SREBP1 as well as diminished expression of PPARα, a transcription factor regulating genes involved in lipid oxidation. In addition, reduced aminoacid catabolism correlates to diminished expression of aminotransferases in liver upon GH treatment. Microarray-based expression profiling of GH actions has not only provided molecular correlates to its known physiological action buts has identified a large number of regulated genes for which physiological function is unknown or poorly understood. This opens the opportunity to increase our understanding of liver physiology and the characterization of novel GH effects.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Isaksson, O. G., Jansson, J. O. & Gause ,I. A. (1982). Growth hormone stimulates longitudinal bone growth directly. Science 216, 1237–9.

    Article  PubMed  CAS  Google Scholar 

  • Isgaard, J., Nilsson, A., Lindahl, A., Jansson, J. O. & Isaksson, O. G. (1986). Effects of local administration of GH and IGF-1 on longitudinal bone growth in rats. Am J Physiol 250, E367–72.

    PubMed  CAS  Google Scholar 

  • Davidson, M. B. (1987). Effect of growth hormone on carbohydrate and lipid metabolism. Endocr Rev 8, 115–31.

    PubMed  CAS  Google Scholar 

  • Kostyo, J. L. (1968). Rapid effects of growth hormone on amino acid transport and protein synthesis. Ann N Y Acad Sci 148, 389–407.

    Article  PubMed  CAS  Google Scholar 

  • Kostyo, J. L. & Nutting, D. F. (1974). Growth hormone and protein metabolism. In Handbook of physiology (Sawyer, W. H. & Knobil, E., eds.), Vol. IV, part 2, pp. 187–210. American Physiology Society, Washington DC.

    Google Scholar 

  • Madsen, K., Friberg, U., Roos, P., Eden, S. & Isaksson, O. (1983). Growth hormone stimulates the proliferation of cultured chondrocytes from rabbit ear and rat rib growth cartilage. Nature 304, 545–7.

    Article  PubMed  CAS  Google Scholar 

  • Billestrup, N. & Nielsen, J. H. (1991). The stimulatory effect of growth hormone, prolactin, and placental lactogen on beta-cell proliferation is not mediated by insulin-like growth factor-I. Endocrinology 129, 883–8.

    PubMed  CAS  Google Scholar 

  • Barnard, R., Ng, K. W., Martin, T. J. & Waters, M. J. (1991). Growth hormone (GH) receptors in clonal osteoblast-like cells mediate a mitogenic response to GH. Endocrinology 128, 1459–64.

    PubMed  CAS  Google Scholar 

  • Slootweg, M. C., Swolin, D., Netelenbos, J. C., Isaksson, O. G. & Ohlsson, C. (1997). Estrogen enhances growth hormone receptor expression and growth hormone action in rat osteosarcoma cells and human osteoblast-like cells. J Endocrinol 155, 159–64.

    Article  PubMed  CAS  Google Scholar 

  • Chen, H. T., Schuler, L. A. & Schultz, R. D. (1998). Growth hormone receptor and regulation of gene expression in fetal lymphoid cells. Mol Cell Endocrinol 137, 21–9.

    Article  PubMed  CAS  Google Scholar 

  • Jeay, S., Sonenshein, G. E., Postel-Vinay, M. C., Kelly, P. A. & Baixeras, E. (2002). Growth hormone can act as a cytokine controlling survival and proliferation of immune cells: New insights into signaling pathways. Mol Cell Endocrinol 188, 1–7.

    Article  PubMed  CAS  Google Scholar 

  • Lombardi, G., Colao, A., Ferone, D., Marzullo, P., Orio, F., Longobardi, S. & Merola, B. (1997). Effect of growth hormone on cardiac function. Horm Res. 48 Suppl 4:38–42. Review.

    Google Scholar 

  • Yoshizato, H., Fujikawa, T., Soya, H., Tanaka, M. & Nakashima, K. (1998). The growth hormone (GH) gene is expressed in the lateral hypothalamus: Enhancement by GH-releasing hormone and repression by restraint stress. Endocrinology 139, 2545–51.

    Article  PubMed  CAS  Google Scholar 

  • Tsushima, T. & Friesen, H. G. (1973). Radioreceptor assay for growth hormone. J Clin Endocrinol Metab 37, 334–7.

    PubMed  CAS  Google Scholar 

  • Leung, D. W., Spencer, S. A., Cachianes, G., Hammonds, R. G., Collins, C., Henzel, W. J., Barnard, R., Waters, M. J. & Wood, W. I. (1987). Growth hormone receptor and serum binding protein: Purification, cloning and expression. Nature 330, 537–43.

    Article  PubMed  CAS  Google Scholar 

  • Cosman, D. (1993). The hematopoietin receptor superfamily. Cytokine 5, 95–106.

    Article  PubMed  CAS  Google Scholar 

  • Argetsinger, L. S., Campbell, G. S., Yang, X., Witthuhn, B. A., Silvennoinen, O., Ihle, J. N. & Carter Su, C. (1993). Identification of JAK2 as a growth hormone receptor-associated tyrosine kinase. Cell 74, 237–44.

    Google Scholar 

  • Carter-Su, C., Argetsinger, L. S., Campbell, G. S., Wang, X., Ihle, J. & Witthuhn, B. (1994). The identification of JAK2 tyrosine kinase as a signaling molecule for growth hormone. Proc Soc Exp Biol Med 206, 210–5.

    PubMed  CAS  Google Scholar 

  • Rosenfeld, R. G., Rosenbloom, A. L. & Guevara-Aguirre, J. (1994). Growth hormone (GH) insensitivity due to primary GH receptor deficiency. Endocr Rev 15, 369–90.

    Article  PubMed  CAS  Google Scholar 

  • Zhou, Y., Xu, B. C., Maheshwari, H. G., He, L., Reed, M., Lozykowski, M., Okada, S., Cataldo, L., Coschigamo, K., Wagner, T. E., Baumann, G. & Kopchick, J. J. (1997). A mammalian model for Laron syndrome produced by targeted disruption of the mouse growth hormone receptor/binding protein gene (the Laron mouse). Proc Natl Acad Sci U S A 94, 13215–20.

    Article  PubMed  CAS  Google Scholar 

  • Sotiropoulos, A., Perrot Applanat, M., Dinerstein, H., Pallier, A., Postel Vinay, M. C., Finidori, J. & Kelly, P. A. (1994). Distinct cytoplasmic regions of the growth hormone receptor are required for activation of JAK2, mitogen-activated protein kinase, and transcription [see comments]. Endocrinology 135, 1292–8.

    Article  PubMed  CAS  Google Scholar 

  • Frank, S. J., Gilliland, G., Kraft, A. S. & Arnold, C. S. (1994). Interaction of the growth hormone receptor cytoplasmic domain with the JAK2 tyrosine kinase. Endocrinology 135, 2228–39.

    Article  PubMed  CAS  Google Scholar 

  • Mathews, L. S., Enberg, B., Norstedt, G., (1989) Regulation of rat growth hormone receptor gene expression. J Biol Chem. 264(17):9905–10.

    PubMed  CAS  Google Scholar 

  • Sjogren, K., Liu, J. L., Blad, K., Skrtic, S., Vidal, O., Wallenius, V., LeRoith, D., Tornell, J., Isaksson, O. G., Jansson, J. O. & Ohlsson, C. (1999). Liver-derived insulin-like growth factor I (IGF-I) is the principal source of IGF-I in blood but is not required for postnatal body growth in mice. Proc Natl Acad Sci U S A 96, 7088–92.

    Article  PubMed  CAS  Google Scholar 

  • Powell-Braxton, L., Hollingshead, P., Giltinan, D., Pitts-Meek, S. & Stewart, T. (1993). Inactivation of the IGF-I gene in mice results in perinatal lethality. Ann N Y Acad Sci 692, 300–1.

    Article  PubMed  CAS  Google Scholar 

  • Powell-Braxton, L., Hollingshead, P., Warburton, C., Dowd, M., Pitts-Meek, S., Dalton, D., Gillett, N. & Stewart, T. A. (1993). IGF-I is required for normal embryonic growth in mice. Genes Dev 7, 2609–17.

    Article  PubMed  CAS  Google Scholar 

  • Yakar, S., Liu, J. L., Stannard, B., Butler, A., Accili, D., Sauer, B. & LeRoith, D. (1999). Normal growth and development in the absence of hepatic insulin-like growth factor I. Proc Natl Acad Sci U S A 96, 7324–9.

    Article  PubMed  CAS  Google Scholar 

  • Haluzik, M., Yakar, S., Gavrilova, O., Setser, J., Boisclair, Y. & LeRoith, D. (2003). Insulin resistance in the liver-specific IGF-1 gene-deleted mouse is abrogated by deletion of the acid-labile subunit of the IGF-binding protein-3 complex: Relative roles of growth hormone and IGF-1 in insulin resistance. Diabetes 52, 2483–9.

    Article  PubMed  CAS  Google Scholar 

  • Goodyer, C. G., Zogopoulos, G., Schwartzbauer, G., Zheng, H., Hendy, G. N. & Menon, R. K. (2001). Organization and evolution of the human growth hormone receptor gene 5′-flanking region. Endocrinology 142, 1923–34.

    Article  PubMed  CAS  Google Scholar 

  • Schwartzbauer, G. & Menon, R. K. (1998). Regulation of growth hormone receptor gene expression. Mol Genet Metab 63, 243–53.

    Article  PubMed  CAS  Google Scholar 

  • Caron, R. W., Jahn, G. A. & Deis, R. P. (1994). Lactogenic actions of different growth hormone preparations in pregnant and lactating rats. J Endocrinol 142, 535–45.

    PubMed  CAS  Google Scholar 

  • Mode, A., Tollet, P., Strom, A., Legraverend, C., Liddle, C. & Gustafsson, J. A. (1992). Growth hormone regulation of hepatic cytochrome P450 expression in the rat. Adv Enzyme Regul 32, 255–63.

    Article  PubMed  CAS  Google Scholar 

  • Flores-Morales, A., Greenhalgh, C. J., Norstedt, G. & Rico-Bautista, E. (2005). Negative regulation of GH receptor signaling. Mol Endocrinol. 20(2):241–253.

    Article  PubMed  CAS  Google Scholar 

  • Palmiter, R. D., Norstedt, G., Gelinas, R. E., Hammer, R. E. & Brinster, R. L. (1983). Metallothionein-human GH fusion genes stimulate growth of mice. Science 222, 809–14.

    Article  PubMed  CAS  Google Scholar 

  • Holloway, A. J., van Laar, R. K., Tothill, R. W. & Bowtell, D. D. (2002). Options available—from start to finish—for obtaining data from DNA microarrays II. Nat Genet 32 Suppl, 481–9.

    Article  PubMed  CAS  Google Scholar 

  • Flores-Morales, A., Stahlberg, N., Tollet-Egnell, P., Lundeberg, J., Malek, R. L., Quackenbush, J., Lee, N. H. & Norstedt, G. (2001). Microarray analysis of the in vivo effects of hypophysectomy and growth hormone treatment on gene expression in the rat. Endocrinology 142, 3163–76.

    Article  PubMed  CAS  Google Scholar 

  • Tollet-Egnell, P., Parini, P., Stahlberg, N., Lonnstedt, I., Lee, N. H., Rudling, M., Flores-Morales, A. & Norstedt, G. (2004). Growth hormone-mediated alteration of fuel metabolism in the aged rat as determined from transcript profiles. Physiol Genomics 16, 261–7.

    PubMed  CAS  Google Scholar 

  • Greenhalgh, C. J., Rico-Bautista, E., Lorentzon, M., Thaus, A. L., Morgan, P. O., Willson, T. A., Zervoudakis, P., Metcalf, D., Street, I., Nicola, N. A., Nash, A. D., Fabri, L. J., Norstedt, G., Ohlsson, C., Flores-Morales, A., Alexander, W. S. & Hilton, D. J. (2005). SOCS2 negatively regulates growth hormone action in vitro and in vivo. J Clin Invest 115, 397–406.

    Article  PubMed  CAS  Google Scholar 

  • Olsson, B., Bohlooly, Y. M., Brusehed, O., Isaksson, O. G., Ahren, B., Olofsson, S. O., Oscarsson, J. & Tornell, J. (2003). Bovine growth hormone-transgenic mice have major alterations in hepatic expression of metabolic genes. Am J Physiol Endocrinol Metab 285, E504–11.

    PubMed  CAS  Google Scholar 

  • Rowland, J. E., Lichanska, A. M., Kerr, L. M., White, M., d’Aniello, E. M., Maher, S. L., Brown, R., Teasdale, R. D., Noakes, P. G. & Waters, M. J. (2005). In vivo analysis of growth hormone receptor signaling domains and their associated transcripts. Mol Cell Biol 25, 66–77.

    Article  PubMed  CAS  Google Scholar 

  • Rastegar, M., Rousseau, G. G. & Lemaigre, F. P. (2000). CCAAT/enhancer-binding protein-alpha is a component of the growth hormone-regulated network of liver transcription factors. Endocrinology 141, 1686–92.

    Article  PubMed  CAS  Google Scholar 

  • Piwien-Pilipuk, G., Van Mater, D., Ross, S. E., MacDougald, O. A. & Schwartz, J. (2001). Growth hormone regulates phosphorylation and function of CCAAT/enhancer-binding protein beta by modulating Akt and glycogen synthase kinase-3. J Biol Chem 276, 19664–71.

    Article  PubMed  CAS  Google Scholar 

  • Liao, J., Piwien-Pilipuk, G., Ross, S. E., Hodge, C. L., Sealy, L., MacDougald, O. A. & Schwartz, J. (1999). CCAAT/enhancer-binding protein beta (C/EBPbeta) and C/EBPdelta contribute to growth hormone-regulated transcription of c-fos. J Biol Chem 274, 31597–604.

    Article  PubMed  CAS  Google Scholar 

  • Meton, I., Boot, E. P., Sussenbach, J. S. & Steenbergh, P. H. (1999). Growth hormone induces insulin-like growth factor-I gene transcription by a synergistic action of STAT5 and HNF-1alpha. FEBS Lett 444, 155–9.

    Article  PubMed  CAS  Google Scholar 

  • Lahuna, O., Rastegar, M., Maiter, D., Thissen, J. P., Lemaigre, F. P. & Rousseau, G. G. (2000). Involvement of STAT5 (signal transducer and activator of transcription 5) and HNF-4 (hepatocyte nuclear factor 4) in the transcriptional control of the hnf6 gene by growth hormone. Mol Endocrinol 14, 285–94.

    Article  PubMed  CAS  Google Scholar 

  • Le Stunff, C. & Rotwein, P. (1998). Growth hormone stimulates interferon regulatory factor-1 gene expression in the liver. Endocrinology 139, 859–66.

    Article  PubMed  CAS  Google Scholar 

  • Yoshioka, S., Okimura, Y., Takahashi, Y., Iida, K., Kaji, H., Matsuo, M. & Chihara, K. (2004). Up-regulation of mitochondrial transcription factor 1 mRNA levels by GH in VSMC. Life Sci 74, 2097–109.

    Article  PubMed  CAS  Google Scholar 

  • Ashcom, G., Gurland, G. & Schwartz, J. (1992). Growth hormone synergizes with serum growth factors in inducing c-fos transcription in 3T3-F442A cells. Endocrinology 131, 1915–21.

    Article  PubMed  CAS  Google Scholar 

  • Gurland, G., Ashcom, G., Cochran, B. H. & Schwartz, J. (1990). Rapid events in growth hormone action. Induction of c-fos and c-jun transcription in 3T3-F442A preadipocytes. Endocrinology 127, 3187–95.

    PubMed  CAS  Google Scholar 

  • Krupczak-Hollis, K., Wang, X., Dennewitz, M. B. & Costa, R. H. (2003). Growth hormone stimulates proliferation of old-aged regenerating liver through forkhead box m1b. Hepatology 38,1552–62.

    PubMed  CAS  Google Scholar 

  • Ziros, P. G., Georgakopoulos, T., Habeos, I., Basdra, E. K. & Papavassiliou, A. G. (2004). Growth hormone attenuates the transcriptional activity of Runx2 by facilitating its physical association with Stat3beta. J Bone Miner Res 19, 1892–904.

    Article  PubMed  CAS  Google Scholar 

  • Zhang, X., Zhu, T., Chen, Y., Mertani, H. C., Lee, K. O. & Lobie, P. E. (2003). Human growth hormone-regulated HOXA1 is a human mammary epithelial oncogene. J Biol Chem 278, 7580–90.

    Article  PubMed  CAS  Google Scholar 

  • Wood, T. J., Sliva, D., Lobie, P. E., Pircher, T. J., Gouilleux, F., Wakao, H., Gustafsson, J. A., Groner, B., Norstedt, G. & Haldosen, L. A. (1995). Mediation of growth hormone-dependent transcriptional activation by mammary gland factor/Stat 5. J Biol Chem 270, 9448–53.

    Article  PubMed  CAS  Google Scholar 

  • Xu, B. C., Wang, X., Darus, C. J. & Kopchick, J. J. (1996). Growth hormone promotes the association of transcription factor STAT5 with the growth hormone receptor. J Biol Chem 271, 19768–73.

    Article  PubMed  CAS  Google Scholar 

  • Zhu, T., Goh, E. L., Graichen, R., Ling, L. & Lobie, P. E. (2001). Signal transduction via the growth hormone receptor. Cell Signal 13, 599–616.

    Article  PubMed  CAS  Google Scholar 

  • Fain, J. N., Ihle, J. H. & Bahouth, S. W. (1999). Stimulation of lipolysis but not of leptin release by growth hormone is abolished in adipose tissue from Stat5a and b knockout mice. Biochem Biophys Res Commun 263, 201–5.

    Article  PubMed  CAS  Google Scholar 

  • Kofoed, E. M., Hwa, V., Little, B., Woods, K. A., Buckway, C. K., Tsubaki, J., Pratt, K. L., Bezrodnik, L., Jasper, H., Tepper, A., Heinrich, J. J. & Rosenfeld, R. G. (2003). Growth hormone insensitivity associated with a STAT5b mutation. N Engl J Med 349, 1139–47.

    Article  PubMed  CAS  Google Scholar 

  • Davey, H. W., McLachlan, M. J., Wilkins, R. J., Hilton, D. J. & Adams, T. E. (1999). STAT5b mediates the GH-induced expression of SOCS-2 and SOCS-3 mRNA in the liver. Mol Cell Endocrinol 158, 111–6.

    Article  PubMed  CAS  Google Scholar 

  • Davey, H. W., Xie, T., McLachlan, M. J., Wilkins, R. J., Waxman, D. J. & Grattan, D. R. (2001). STAT5b is required for GH-induced liver IGF-I gene expression. Endocrinology 142, 3836–41.

    Article  PubMed  CAS  Google Scholar 

  • Woelfle, J. & Rotwein, P. (2004). In vivo regulation of growth hormone-stimulated gene transcription by STAT5b. Am J Physiol Endocrinol Metab 286, E393–401.

    Article  PubMed  CAS  Google Scholar 

  • Lahuna, O., Fernández, L., Karlsson, H., Maiter, D., Lemaigre, F. P., Rousseau, G. G., Gustafsson, J. & Mode, A. (1997). Expression of hepatocyte nuclear factor 6 in rat liver is sex-dependent and regulated by growth hormone. Proc Natl Acad Sci U S A 94, 12309–13.

    Article  PubMed  CAS  Google Scholar 

  • Litterst, C. M., Kliem, S., Marilley, D. & Pfitzner, E. (2003). NCoA-1/SRC-1 is an essential coactivator of STAT5 that binds to the FDL motif in the alpha-helical region of the STAT5 transactivation domain. J Biol Chem 278, 45340–51.

    Article  PubMed  CAS  Google Scholar 

  • Zhu, M., John, S., Berg, M. & Leonard, W. J. (1999). Functional association of Nmi with Stat5 and Stat1 in IL-2- and IFNgamma-mediated signaling. Cell 96, 121–30.

    Article  PubMed  CAS  Google Scholar 

  • Nakajima, H., Brindle, P. K., Handa, M. & Ihle, J. N. (2001). Functional interaction of STAT5 and nuclear receptor co-repressor SMRT: Implications in negative regulation of STAT5-dependent transcription. Embo J 20, 6836–44.

    Article  PubMed  CAS  Google Scholar 

  • Martino, A., Holmes, J. H. T., Lord, J. D., Moon, J. J. & Nelson, B. H. (2001). Stat5 and Sp1 regulate transcription of the cyclin D2 gene in response to IL-2. J Immunol 166, 1723–9.

    PubMed  CAS  Google Scholar 

  • Bergad, P. L., Towle, H. C. & Berry, S. A. (2000). Yin-yang 1 and glucocorticoid receptor participate in the Stat5-mediated growth hormone response of the serine protease inhibitor 2.1 gene. J Biol Chem 275, 8114–20.

    Article  PubMed  CAS  Google Scholar 

  • Wyszomierski, S. L. & Rosen, J. M. (2001). Cooperative effects of STAT5 (signal transducer and activator of transcription 5) and C/EBPbeta (CCAAT/enhancer-binding protein-beta) on beta-casein gene transcription are mediated by the glucocorticoid receptor. Mol Endocrinol 15, 228–40.

    Article  PubMed  CAS  Google Scholar 

  • Stocklin, E., Wissler, M., Gouilleux, F. & Groner, B. (1996). Functional interactions between Stat5 and the glucocorticoid receptor. Nature 383, 726–8.

    Article  PubMed  CAS  Google Scholar 

  • Tronche, F., Opherk, C., Moriggl, R., Kellendonk, C., Reimann, A., Schwake, L., Reichardt, H. M., Stangl, K., Gau, D., Hoeflich, A., Beug, H., Schmid, W. & Schutz, G. (2004). Glucocorticoid receptor function in hepatocytes is essential to promote postnatal body growth. Genes Dev 18, 492–7.

    Article  PubMed  CAS  Google Scholar 

  • Zhou, Y. C. & Waxman, D. J. (1999). STAT5b down-regulates peroxisome proliferator-activated receptor alpha transcription by inhibition of ligand-independent activation function region-1 trans-activation domain. J Biol Chem 274, 29874–82.

    Article  PubMed  CAS  Google Scholar 

  • Carlsson, L., Linden, D., Jalouli, M. & Oscarsson, J. (2001). Effects of fatty acids and growth hormone on liver fatty acid binding protein and PPARalpha in rat liver. Am J Physiol Endocrinol Metab 281, E772–81.

    PubMed  CAS  Google Scholar 

  • Tata, J. (1970). Regulation of protein synthesis by growth and developmental hormones. Biochemical Actions of Hormones (Litwack, G., Ed.),pp. 89–129, Academic Press, New York.

    Google Scholar 

  • Engel, F. & Kostyo, J. (1964). Metabolic actions of pituitary hormones. The Hormones (Pincus, G., Thimann, K. V. & Astwood, E., Eds.), V, Academic Press, New York.

    Google Scholar 

  • Kostyo, J. & Nutting, D. (1974). Growth hormone and protein metabolism. Handbook of Physiology (Sawyer, W. H. & Knobil, E., Eds.), pp. 187–210, American Physiology Society, Washington DC.

    Google Scholar 

  • Kostyo, J. L. & Isaksson, O. (1977). Growth hormone and the regulation of somatic growth. Int Rev Physiol 13, 255–74.

    PubMed  CAS  Google Scholar 

  • Goodman, H. & Schwartz, J. (1974). Growth hormone and lipid metabolism. Handbook of Physiology, (Knobil, E. & Swayer W. H. Eds.), American Physiology Society, pp. 211–231. American Physiology Society, Washington DC.

    Google Scholar 

  • Lagreid, A., Hvidsten, T. R., Midelfart, H., Komorowski, J. & Sandvik, A. K. (2003). Predicting gene ontology biological process from temporal gene expression patterns. Genome Res 13, 965–79.

    Article  PubMed  CAS  Google Scholar 

  • Sjoberg, A., Oscarsson, J., Boren, J., Eden, S. & Olofsson, S. O. (1996). Mode of growth hormone administration influences triacylglycerol synthesis and assembly of apolipoprotein B-containing lipoproteins in cultured rat hepatocytes. J Lipid Res 37, 275–89.

    PubMed  CAS  Google Scholar 

  • Sjoberg, A., Oscarsson, J., Eden, S. & Olofsson, S. O. (1994). Continuous but not intermittent administration of growth hormone to hypophysectomized rats increases apolipoprotein-E secretion from cultured hepatocytes. Endocrinology 134, 790–8.

    Article  PubMed  CAS  Google Scholar 

  • Sjoberg, A., Oscarsson, J., Bostrom, K., Innerarity, T. L., Eden, S. & Olofsson, S. O. (1992). Effects of growth hormone on apolipoprotein-B (apoB) messenger ribonucleic acid editing, and apoB 48 and apoB 100 synthesis and secretion in the rat liver. Endocrinology 130, 3356–64.

    Article  PubMed  CAS  Google Scholar 

  • Horton, J. D., Shah, N. A., Warrington, J. A., Anderson, N. N., Park, S. W., Brown, M. S. & Goldstein, J. L. (2003). Combined analysis of oligonucleotide microarray data from transgenic and knockout mice identifies direct SREBP target genes. Proc Natl Acad Sci U S A 100, 12027–32.

    Article  PubMed  CAS  Google Scholar 

  • Jalouli, M., Carlsson, L., Ameen, C., Linden, D., Ljungberg, A., Michalik, L., Eden, S., Wahli, W. & Oscarsson, J. (2003). Sex difference in hepatic peroxisome proliferator-activated receptor alpha expression: Influence of pituitary and gonadal hormones. Endocrinology 144, 101–9.

    Article  PubMed  CAS  Google Scholar 

  • Zhang, Y. & Dufau, M. L. (2004). Gene silencing by nuclear orphan receptors. Vitam Horm 68, 1–48.

    PubMed  CAS  Google Scholar 

  • Watanabe, M., Houten, S. M., Wang, L., Moschetta, A., Mangelsdorf, D. J., Heyman, R. A., Moore, D. D. & Auwerx, J. (2004). Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c. J Clin Invest 113, 1408–18.

    Article  PubMed  CAS  Google Scholar 

  • Kullak-Ublick, G. A., Stieger, B. & Meier, P. J. (2004). Enterohepatic bile salt transporters in normal physiology and liver disease. Gastroenterology 126, 322–42.

    Article  PubMed  CAS  Google Scholar 

  • Falany, C. N., Xie, X., Wheeler, J. B., Wang, J., Smith, M., He, D. & Barnes, S. (2002). Molecular cloning and expression of rat liver bile acid CoA ligase. J Lipid Res 43, 2062–71.

    Article  PubMed  CAS  Google Scholar 

  • Gartner, L. M. & Arias, I. M. (1972). Hormonal control of hepatic bilirubin transport and conjugation. Am J Physiol 222, 1091–9.

    PubMed  CAS  Google Scholar 

  • Rudling, M., Parini, P. & Angelin, B. (1997). Growth hormone and bile acid synthesis. Key role for the activity of hepatic microsomal cholesterol 7alpha-hydroxylase in the rat. J Clin Invest 99, 2239–45.

    Article  PubMed  CAS  Google Scholar 

  • Boulias, K., Katrakili, N., Bamberg, K., Underhill, P., Greenfield, A. & Talianidis, I. (2005). Regulation of hepatic metabolic pathways by the orphan nuclear receptor SHP. EMBO J 24, 2624–33.

    Article  PubMed  CAS  Google Scholar 

  • Ameen, C. & Oscarsson, J. (2003). Sex difference in hepatic microsomal triglyceride transfer protein expression is determined by the growth hormone secretory pattern in the rat. Endocrinology 144, 3914–21.

    Article  PubMed  CAS  Google Scholar 

  • Chakravarthy, M. V., Pan, Z., Zhu, Y., Tordjman, K., Schneider, J. G., Coleman, T., Turk, J. & Semenkovich, C. F. (2005). “New” hepatic fat activates PPARalpha to maintain glucose, lipid, and cholesterol homeostasis. Cell Metab 1, 309–22.

    Article  PubMed  CAS  Google Scholar 

  • Abu-Elheiga, L., Matzuk, M. M., Abo-Hashema, K. A. & Wakil, S. J. (2001). Continuous fatty acid oxidation and reduced fat storage in mice lacking acetyl-CoA carboxylase 2. Science 291, 2613–6.

    Article  PubMed  CAS  Google Scholar 

  • Pennacchio, L. A. & Rubin, E. M. (2003). Apolipoprotein A5, a newly identified gene that affects plasma triglyceride levels in humans and mice. Arterioscler Thromb Vasc Biol 23, 529–34.

    Article  PubMed  CAS  Google Scholar 

  • Shah, P. K., Kaul, S., Nilsson, J. & Cercek, B. (2001). Exploiting the vascular protective effects of high-density lipoprotein and its apolipoproteins: An idea whose time for testing is coming, part I. Circulation 104, 2376–83.

    Article  PubMed  CAS  Google Scholar 

  • Terauchi, Y., Tsuji, Y., Satoh, S., Minoura, H., Murakami, K., Okuno, A., Inukai, K., Asano, T., Kaburagi, Y., Ueki, K., Nakajima, H., Hanafusa, T., Matsuzawa, Y., Sekihara, H., Yin, Y., Barrett, J. C., Oda, H., Ishikawa, T., Akanuma, Y., Komuro, I., Suzuki, M., Yamamura, K., Kodama, T., Suzuki, H., Yamamura, K., Kodama, T., Suzuki, H., Koyasu, S., Aizawa, S., Tobe, K., Fukui, Y., Yazaki, Y. & Kadowaki, T. (1999). Increased insulin sensitivity and hypoglycaemia in mice lacking the p85 alpha subunit of phosphoinositide 3-kinase. Nat Genet 21, 230–5.

    Article  PubMed  CAS  Google Scholar 

  • Luo, J., Field, S. J., Lee, J. Y., Engelman, J. A. & Cantley, L. C. (2005). The p85 regulatory subunit of phosphoinositide 3-kinase down-regulates IRS-1 signaling via the formation of a sequestration complex. J Cell Biol 170, 455–64.

    Article  PubMed  CAS  Google Scholar 

  • Mathews, S. T., Singh, G. P., Ranalletta, M., Cintron, V. J., Qiang, X., Goustin, A. S., Jen, K. L., Charron, M. J., Jahnen-Dechent, W. & Grunberger, G. (2002). Improved insulin sensitivity and resistance to weight gain in mice null for the Ahsg gene. Diabetes 51, 2450–8.

    Article  PubMed  CAS  Google Scholar 

  • Liu, J., DeYoung, S. M., Hwang, J. B., O’Leary, E. E. & Saltiel, A. R. (2003). The roles of Cbl-b and c-Cbl in insulin-stimulated glucose transport. J Biol Chem 278, 36754–62.

    Article  PubMed  CAS  Google Scholar 

  • Mitra, P., Zheng, X. & Czech, M. P. (2004). RNAi-based analysis of CAP, Cbl, and CrkII function in the regulation of GLUT4 by insulin. J Biol Chem 279, 37431–5.

    Article  PubMed  CAS  Google Scholar 

  • Cheung, N. W., Liddle, C., Coverdale, S., Lou, J. C. & Boyages, S. C. (1996). Growth hormone treatment increases cytochrome P450-mediated antipyrine clearance in man. J Clin Endocrinol Metab 81, 1999–2001.

    Article  PubMed  CAS  Google Scholar 

  • Rendic, S. & Di Carlo, F. J. (1997). Human cytochrome P450 enzymes: A status report summarizing their reactions, substrates, inducers, and inhibitors. Drug Metab Rev 29, 413–580.

    PubMed  CAS  Google Scholar 

  • MacGeoch, C., Morgan, E. T., Halpert, J. & Gustafsson, J. A. (1984). Purification, characterization, and pituitary regulation of the sex-specific cytochrome P-450 15 beta-hydroxylase from liver microsomes of untreated female rats. J Biol Chem 259, 15433–9.

    PubMed  CAS  Google Scholar 

  • Mode, A., Gustafsson, J. A., Jansson, J. O., Eden, S. & Isaksson, O. (1982). Association between plasma level of growth hormone and sex differentiation of hepatic steroid metabolism in the rat. Endocrinology 111, 1692–7.

    PubMed  CAS  Google Scholar 

  • Westin, S., Strom, A., Gustafsson, J. A. & Zaphiropoulos, P. G. (1990). Growth hormone regulation of the cytochrome P-450IIC subfamily in the rat: Inductive, repressive, and transcriptional effects on P-450f (IIC7) and P-450PB1 (IIC6) gene expression. Mol Pharmacol 38, 192–7.

    PubMed  CAS  Google Scholar 

  • Mode, A., Wiersma-Larsson, E.&Gustafsson, J. A. (1989). Transcriptional and posttranscriptional regulation of sexually differentiated rat liver cytochrome P-450 by growth hormone. Mol Endocrinol 3, 1142–7.

    PubMed  CAS  Google Scholar 

  • Ahluwalia, A., Clodfelter, K. H. & Waxman, D. J. (2004). Sexual dimorphism of rat liver gene expression: Regulatory role of growth hormone revealed by deoxyribonucleic acid microarray analysis. Mol Endocrinol 18, 747–60.

    Article  PubMed  CAS  Google Scholar 

  • Stahlberg, N., Merino, R., Hernández, L. H., Fernández-Pérez, L., Sandelin, A., Engstrom, P., Tollet-Egnell, P., Lenhard, B. & Flores-Morales, A. (2005). Exploring hepatic hormone actions using a compilation of gene expression profiles. BMC Physiol 5, 8.

    Article  PubMed  CAS  Google Scholar 

  • Chang, T. K., Teixeira, J., Gil, G. & Waxman, D. J. (1993). The lithocholic acid 6 beta-hydroxylase cytochrome P-450, CYP 3A10 is an active catalyst of steroid-hormone 6 beta-hydroxylation. Biochem J 291 (Pt 2), 429–33.

    PubMed  CAS  Google Scholar 

  • Thummel, K. E. & Wilkinson, G. R. (1998). In vitro and in vivo drug interactions involving human CYP3A. Annu Rev Pharmacol Toxicol 38, 389–430.

    Article  PubMed  CAS  Google Scholar 

  • Choi, H. S., Chung, M., Tzameli, I., Simha, D., Lee, Y. K., Seol, W. & Moore, D. D. (1997). Differential transactivation by two isoforms of the orphan nuclear hormone receptor CAR. J Biol Chem 272, 23565–71.

    Article  PubMed  CAS  Google Scholar 

  • Holck, H. G. O., Munir, A.K., Mills, L. & Smith, E.L. (1937). Studies upon the sex difference in rats in tolerance to certain barbiturates and to nicotine. J Pharmacol Exp Ther 60, 323–346.

    CAS  Google Scholar 

  • Shapiro, B. H. (1986). Sexually dimorphic response of rat hepatic monooxygenases to low-dose phenobarbital. Biochem Pharmacol 35, 1766–8.

    Article  PubMed  CAS  Google Scholar 

  • Mulder, G. J. (1986). Sex differences in drug conjugation and their consequences for drug toxicity. Sulfation, glucuronidation, and glutathione conjugation. Chem Biol Interact 57, 1–15.

    Article  PubMed  CAS  Google Scholar 

  • Srivastava, P. K. & Waxman, D. J. (1993). Sex-dependent expression and growth hormone regulation of class alpha and class mu glutathione S-transferase mRNAs in adult rat liver. Biochem J 294 (Pt 1), 159–65.

    PubMed  CAS  Google Scholar 

  • Zhu, B. T., Suchar, L. A., Huang, M. T. & Conney, A. H. (1996). Similarities and differences in the glucuronidation of estradiol and estrone by UDP-glucuronosyltransferase in liver microsomes from male and female rats. Biochem Pharmacol 51, 1195–202.

    Article  PubMed  CAS  Google Scholar 

  • Runge-Morris, M. & Wilusz, J. (1991). Age- and gender-related gene expression of hydroxysteroid sulfotransferase-a in rat liver. Biochem Biophys Res Commun 175, 1051–6.

    Article  PubMed  CAS  Google Scholar 

  • Fletcher, C. V., Acosta, E. P. & Strykowski, J. M. (1994). Gender differences in human pharmacokinetics and pharmacodynamics. J Adolesc Health 15, 619–29.

    Article  PubMed  CAS  Google Scholar 

  • Veldhuis, J. D. (1996). New modalities for understanding dynamic regulation of the somatotropic (GH) axis: Explication of gender differences in GH neuroregulation in the human. J Pediatr Endocrinol Metab 9 Suppl 3, 237–53.

    PubMed  Google Scholar 

  • Winer, L. M., Shaw, M. A. & Baumann, G. (1990). Basal plasma growth hormone levels in man: New evidence for rhythmicity of growth hormone secretion. J Clin Endocrinol Metab 70, 1678–86.

    Article  PubMed  CAS  Google Scholar 

  • Grofte, T., Wolthers, T., Jensen, S. A., Moller, N., Jorgensen, J. O., Tygstrup, N., Orskov, H. & Vilstrup, H. (1997). Effects of growth hormone and insulin-like growth factor-I singly and in combination on in vivo capacity of urea synthesis, gene expression of urea cycle enzymes, and organ nitrogen contents in rats. Hepatology 25, 964–9.

    Article  PubMed  CAS  Google Scholar 

  • Kurtz, A., Zapf, J., Eckardt, K. U., Clemons, G., Froesch, E. R. & Bauer, C. (1988). Insulin-like growth factor I stimulates erythropoiesis in hypophysectomized rats. Proc Natl Acad Sci U S A 85, 7825–9.

    Article  PubMed  CAS  Google Scholar 

  • Anderson, G. J., Frazer, D. M., McKie, A. T., Vulpe, C. D. & Smith, A. (2005). Mechanisms of haem and non-haem iron absorption: Lessons from inherited disorders of iron metabolism. Biometals 18, 339–48.

    Article  PubMed  CAS  Google Scholar 

  • Bornfeldt, K. E., Arnqvist, H. J., Enberg, B., Mathews, L. S. & Norstedt, G. (1989). Regulation of insulin-like growth factor-I and growth hormone receptor gene expression by diabetes and nutritional state in rat tissues. J Endocrinol 122, 651–6.

    PubMed  CAS  Google Scholar 

  • Straus, D. S. & Takemoto, C. D. (1990). Effect of fasting on insulin-like growth factor-I (IGF-I) and growth hormone receptor mRNA levels and IGF-I gene transcription in rat liver. Mol Endocrinol 4, 91–100.

    PubMed  CAS  Google Scholar 

  • Martínez, V., Balbín, M., Ordóñez, F. A., Rodríguez, J., García, E., Medina, A. & Santos, F. (1999). Hepatic expression of growth hormone receptor/binding protein and insulin-like growth factor I genes in uremic rats. Influence of nutritional deficit. Growth Horm IGF Res 9, 61–8.

    Article  PubMed  Google Scholar 

  • Brameld, J. M., Gilmour, R. S. & Buttery, P. J. (1999). Glucose and amino acids interact with hormones to control expression of insulin-like growth factor-I and growth hormone receptor mRNA in cultured pig hepatocytes. J Nutr 129, 1298–306.

    PubMed  CAS  Google Scholar 

  • Chung, C. S. & Etherton, T. D. (1986). Characterization of porcine growth hormone (pGH) binding to porcine liver microsomes: Chronic administration of pGH induces pGH binding. Endocrinology 119, 780–6.

    PubMed  CAS  Google Scholar 

  • Gluckman, P. D., Breier, B. H. & Sauerwein, H. (1990). Regulation of the cell surface growth hormone receptor. Acta Paediatr Scand Suppl 366, 73–8.

    PubMed  CAS  Google Scholar 

  • Posner, B. I., Patel, B., Vezinhet, A. & Charrier, J. (1980). Pituitary-dependent growth hormone receptors in rabbit and sheep liver. Endocrinology 107, 1954–8.

    PubMed  CAS  Google Scholar 

  • Maiter, D., Underwood, L. E., Maes, M. & Ketelslegers, J. M. (1988). Acute down-regulation of the somatogenic receptors in rat liver by a single injection of growth hormone. Endocrinology 122, 1291–6.

    PubMed  CAS  Google Scholar 

  • Chen, N. Y., Chen, W. Y. & Kopchick, J. J. (1997). Liver and kidney growth hormone (GH) receptors are regulated differently in diabetic GH and GH antagonist transgenic mice. Endocrinology 138, 1988–94.

    Article  PubMed  CAS  Google Scholar 

  • Camarillo, I. G., Thordarson, G., Ilkbahar, Y. N. & Talamantes, F. (1998). Development of a homologous radioimmunoassay for mouse growth hormone receptor. Endocrinology 139, 3585–9.

    Article  PubMed  CAS  Google Scholar 

  • Bennett, P. A., Levy, A., Carmignac, D. F., Robinson, I. C. & Lightman, S. L. (1996). Differential regulation of the growth hormone receptor gene: Effects of dexamethasone and estradiol. Endocrinology 137, 3891–6.

    Article  PubMed  CAS  Google Scholar 

  • Leung, K. C., Doyle, N., Ballesteros, M., Waters, M. J. & Ho, K. K. (2000). Insulin regulation of human hepatic growth hormone receptors: Divergent effects on biosynthesis and surface translocation. J Clin Endocrinol Metab 85, 4712–20.

    Article  PubMed  CAS  Google Scholar 

  • Ji, S., Guan, R., Frank, S. J. & Messina, J. L. (1999). Insulin inhibits growth hormone signaling via the growth hormone receptor/JAK2/STAT5B pathway. J Biol Chem 274, 13434–42.

    Article  PubMed  CAS  Google Scholar 

  • Mullis, P. E., Eble, A., Marti, U., Burgi, U. & Postel-Vinay, M. C. (1999). Regulation of human growth hormone receptor gene transcription by triiodothyronine (T3). Mol Cell Endocrinol 147, 17–25.

    Article  PubMed  CAS  Google Scholar 

  • Mirpuri, E., García-Trevijano, E. R., Castilla-Cortázar, I., Berasain, C., Quiroga, J., Rodríguez-Ortigosa, C., Mato, J. M., Prieto, J. & Avila, M. A. (2002). Altered liver gene expression in CCl4-cirrhotic rats is partially normalized by insulin-like growth factor-I. Int J Biochem Cell Biol 34, 242–52.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. Amilcar Flores-Morales PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Leandro Fernández-Pérez MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Cincinnati Children’s Hospital Medical Center (CCHMC), University of Cincinnati College of Medicine, 3333 Burnett Avenue, Cincinnati, OH 45229, USA

    Stuart Handwerger MD

  2. University of Cincinnati College of Medicine, Cincinnati, OH, USA

    Bruce Aronow PhD

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Humana Press

About this chapter

Cite this chapter

Flores-Morales, A., Fernández-Pérez, L. (2008). Analysis of Growth Hormone Effects on Hepatic Gene Expression in Hypophysectomized Rats. In: Handwerger, S., Aronow, B. (eds) Genomics in Endocrinology. Contemporary Endocrinology. Humana Press. https://doi.org/10.1007/978-1-59745-309-7_3

Download citation

  • DOI: https://doi.org/10.1007/978-1-59745-309-7_3

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-651-1

  • Online ISBN: 978-1-59745-309-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation