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Poult Sci 2007. 86:423-430
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RAPID COMMUNICATION

Cloning of Chicken Glucocorticoid Receptor (GR) and Characterization of its Expression in Pituitary and Extrapituitary Tissues

A. H. Y. Kwok, Y. Wang, C. Y. Wang and F. C. Leung1

Department of Zoology, The University of Hong Kong, Hong Kong, China

1 Corresponding author: fcleung{at}hkucc.hku.hk


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Substantial evidence suggests that glucocorticoids play critical roles in the differentiation of somatotroph and lactotroph in embryonic pituitaries of birds. However, the basic information on the expression of glucocorticoid receptor (GR) in avian species is limited. In this study, the full-length cDNA for chicken GR was cloned from the chicken kidney. It encodes 772 amino acids and shares high homology with that of the human (73%), mouse (73%), rat (71%), rabbit (72%), and trout (51%) sequences. Similar to mammals, chicken GR is widely expressed in all adult tissues being investigated. Among the 12 tissues investigated, relatively high expression of GR was detected in pituitary, muscle, ovary, and kidney using reverse transcription-PCR assay. Using semiquantitative reverse transcription-PCR, GR is shown to be abundantly expressed at a more or less constant level during embryonic pituitary development (from d 8 to 20), supporting the hypothesis that the expression of GR is unlikely to be a limiting factor in initiating the differentiation of somatotroph and lactotroph in embryonic pituitary of birds. Moreover, an abundant expression of GR in the whole embryos at earlier developmental stages (from d 2 to 5) was also detected in the present study, though its physiological relevance remains to be determined.

Key Words: glucocorticoid receptor • pituitary • embryo • chicken


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Glucocorticoids (GC), an essential class of stress-induced endogenous steroid hormones under control of the hypothalamic-pituitary-adrenal axis, affect virtually all tissues and regulate various biologically important functions, from metabolism, behavior, immune response to growth and development in cell type-specific manner (Mangelsdorf et al., 1995). Most, if not all, of these effects are mediated by the GC receptors (GR). Glucocorticoid receptor belongs to the nuclear hormone receptor superfamily, which also includes mineralocorticoid receptor (MR), estrogen receptor, progesterone receptor, and androgen receptor (Mangelsdorf et al., 1995). All members are known as ligand-activated transcription factors and are constitutively consisted of 3 major domains: an N-terminal domain carrying a transactivation region (AF-1/tau-1/enh2; Giguere et al., 1986; Dieken and Miesfeld, 1992), a central DNA-binding domain responsible for binding to a specific DNA element and nuclear export (Giguere et al., 1986; Black et al., 2001; Kumar and Thompson, 2005), and a C-terminal ligand-binding domain containing ligand-dependent transcriptional activation function (AF-2) domain and responsible for receptor dimerization (Giguere et al., 1986; Tang et al., 1998).

Glucocorticoid receptor modulates target gene transcription through direct interactions with a specific cis DNA element, enhancing transcription when it binds to a GC response element or suppressing transcription when it binds to a negative GC response element. It is also proposed that GR modulates gene transcription via crosstalk with other transcription factors such as activator protein-1 (Schule et al., 1990; Caelles et al., 1997; Hirasawa et al., 1998), nuclear factor-{kappa}B (McKay and Cidlowski, 2000), members from the signal transduction and activator of transcription factor family (Stocklin et al., 1996; Zhang et al., 1997), and Smads (Song et al., 1999).

Glucocorticoids regulate embryonic development at various levels of the hypothalamic-pituitary-adrenal axis. They directly affect growth hormone and prolactin synthesis in cultured pituitary cells (Nogami and Tachibana, 1993; Nogami et al., 1997; Bossis and Porter, 2003; Fu and Porter, 2004; Nogami et al., 2005). They are also shown to regulate both growth hormone-releasing hormone synthesis in the hypothalamus and its growth hormone-releasing hormone receptor expression in rat and chicken pituitary (Senaris et al., 1996; Miller and Mayo, 1997; Nogami et al., 1999; Bossis and Porter, 2003; Nogami et al., 2005; Porter et al., 2006). Recent studies have proposed that pituitary expression of GR during chicken embryonic development may contribute to somatotroph and lacto-troph differentiation (Dean and Porter, 1999; Bossis and Porter, 2003; Bossis et al., 2004; Fu and Porter, 2004; Porter, 2005). Thus, the expression of GR appears to be another critical point in controlling the differentiation of somatotroph and lactotroph in embryonic pituitaries.

The full-length cDNA for GR are cloned and characterized in several mammalian species including human (Hollenberg et al., 1985), mouse (Francke and Gehring, 1980), rat (Miesfeld et al., 1986), and rabbit (James et al., 2003), and in teleost fish, like trout (Gao et al., 1994). However, it is yet to be cloned in the avian species. Therefore, in this study, we aim to investigate the presence of GR expression in chickens, and if so, its temporal expression during embryonic pituitary development and spatial expression in adult chickens.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Bird Tissues
Adult chickens and chicken embryos were provided by Kadoorie Agricultural Research Center. All embryos were incubated at 37.5° C in a humidified incubator. Chicken pituitaries from embryonic d 8 (E8), 12 (E12), 16 (E16), and 20 (E20) were isolated and separated from the attached brain tissue carefully under a dissection microscope. Embryos from d 2, 3, 4, and 5 were rapidly frozen in liquid N. Adult chickens 25 wk old were decapitated, and 12 different tissues (including brain, pituitary, lung, heart, liver, kidney, intestine, pancreas, breast muscle, spleen, ovary, and testis) were collected for total RNA extraction. Whole ovary was used in the present study, though large yolky follicles (F5 to F1) were removed due to difficulty encountered in RNA extraction.

Cloning the Full-Length cDNA of Chicken GR
Based on the predicted sequence for chicken GR (Gen-Bank accession no. XM_414659), 2 gene-specific primers (GR-rL1 and GR-rL2) were designed to amplify the 5' cDNA ends of GR using the SMART RACE kit (Clontech Laboratories Inc., Palo Alto, CA; Table 1Go). The amplified fragment was cloned into pBluescript SK (±) through TA cloning (Stratagene Inc., La Jolla, CA), followed by sequencing analysis (PE Biosystems, Foster City, CA). To obtain the full-length cDNA of GR, 2 new gene-specific primers (GR-U1-2 and GR-L1) flanking both start and stop codon were designed (Table 1Go). A full-length cDNA was amplified from the adult chicken kidney by using the Expand High FidelityPLUS PCR System (Roche Diagnostics, Basel, Switzerland). This cDNA was cloned into pBluescript SK (+) through TA cloning (Stratagene Inc.). The full-length cDNA of GR was finally determined by sequencing 2 independent clones containing whole open reading frame regions and other clones containing partial cDNA.


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  		Table 1. Primers used
 
RNA Extraction, Reverse Transcription PCR, and Semiquantitative Reverse Transcription PCR
Total RNA was extracted from pituitaries and 11 different adult tissues using TRI Reagent (Molecular Research Center, Cincinnati, OH), according to the manufacturer’s instructions. Reverse transcription (RT) was performed at 42° C for 2 h in a total volume of 10 µL consisting of 2µ g of RNA, 1 x PCR buffer, 10 mM dithiothreitol, 0.5 µM each deoxynucleoside triphosphate, 0.5 µg of oligo(dT), and 100 U of SuperScript II (Invitrogen Corp., Carlsbad, CA). One microliter of the first-strand cDNA was used as the template for each PCR reaction. According to our previously established methods (Wang and Ge, 2003, 2004; Wang et al., 2003, 2006), a semiquantitative RT-PCR assay was also performed to examine the expression of GR in the embryonic pituitaries from E8, E12, E16, and E20. The PCR was performed under the following conditions: 2 min at 95° C for denaturation, followed by 23 cycles (for ß-actin: 30 s at 95° C, 30 s at 62° C, and 30 s at 72° C), 29 cycles (for GR: 30 s at 95° C, 30 s at 58° C, and 30 s at 72° C) of reactions, ending with a 10-min extension at 72° C. The primers used are listed in Table 1Go. The PCR products were electrophoresized in 2% agarose gels, stained with ethidium bromide, and visualized under ultraviolet illumination. The intensity of each band was quantified using Quantity One software (BioRad Laboratories Inc., Hercules, CA).

Data Analysis
The mRNA level of the gene was first calculated relative to that of ß-actin (which was amplified as the internal control). Then it was expressed as the percentage of the mRNA level at E8. The data were analyzed by 1-way ANOVA followed by Dunnett’s test.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Cloning of Full-Length cDNA for Chicken GR
The full-length cDNA for chicken GR is 2,319 bp (Gen-Bank accession no. DQ227738 [GenBank] ) and encodes a precursor of 772 amino acids, which shares high sequence identity with that of human (73%; Hollenberg et al., 1985), mouse (73%; Francke and Gehring, 1980), rat (71%; Miesfeld et al., 1986), rabbit (72%; James et al., 2003), and trout (51%; Gao et al., 1994), as shown in Figure 1Go. Comparison of the GR cDNA sequence with the chicken genome database (http://www.ensembl.org/Gallus_gallus) revealed that the gr gene is located on chromosome 13 and consists of 9 exons (Figure 2Go). Exon 1 consists solely of 5' untranslated region, whereas the coding region stretches from exon 2 to 9. Exon 2 encodes the N-terminal domain containing the transactivation domain (AF-1/tau-1/enh2); exons 3 and 4 encode the central DNA-binding domain; exons 5 to 9 encode the C-terminal ligand-binding domain; and part of exon 9 contains 3' untranslated region. The predicted GenBank sequence shows great discrepancies from our cloned full-length chicken GR (cGR) cDNA. The 5' region of the predicted sequence (approximately 700 bp) shows no homology to our cGR and GR from other species, and it does not include the transactivation domain (tau-1). An insertion of 200 bp, not found in our cGR and GR from other species, is observed within exon 3, which interrupts coding of the DNA-binding domain (Figure 2Go).


Figure 1
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  		Figure 1. Amino acid sequence alignment of chicken glucocorticoid receptor (cGR) with that of the human (hGR), rat (rGR), mouse (mGR), and trout (tGR). Boxed amino acid residues (Met) are the putative internal translation initiation sites in the N-terminus of GR. The activation functional domain (AF-1/tau-1) is shaded and underlined. The DNA-binding domain (DBD) and ligand-binding domain (LBD) are underlined and shaded, respectively. The conserved amino acid residues in DBD, including 8 Cys for Zn binding and pair of phenylalanines (FF) critical for nuclear export, are boxed. The dots represent amino acid residues identical to cGR (panel A). Phylogenetic tree (constructed by neighbor-joining method) showing the evolutionary relationships among GR in different species. Numbers adjacent to the branch point indicate the bootstrap values (panel B).

 

Figure 2
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  		Figure 2. Amino acid sequence alignment of cloned chicken glucocorticoid receptor (cGR; cloned-cGR: DQ227738) with that of predicted cGR (predicted-cGR: XM_414659). Only the boxed regions (363 amino acids) are identical, whereas other regions show no sequence identity. The activation functional domain (AF-1/tau-1) is shaded (panel A). Genomic organization of cGR receptor. Nine exons are labeled with E1 to E9, respectively. The arrows indicate the location of translation initiation site (ATG) and stop site (TGA). Dots represent amino acid residues identical to cloned cGR (panel B).

 
Tissue Distribution of GR Expression
To examine the mRNA expression of GR in adult chicken tissues, RT-PCR assay was used. As shown in Figure 3Go, GR is widely expressed in all 12 tissues investigated, including brain, pituitary, lung, heart, liver, kidney, intestine, pancreas, breast muscle, spleen, ovary, and testis. We detected relatively high expression of GR in pituitary, muscle, ovary, and kidney (Figure 3Go). In contrast, no PCR band could be detected in all negative controls (data not shown).


Figure 3
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  		Figure 3. Expression of glucocorticoid receptor (GR) in adult chicken tissues. Numbers in parentheses indicate the PCR cycle numbers used.

 
Expression of GR in Early Embryos and Embryonic Pituitaries
The expression of GR in embryonic pituitaries was studied using semiquantitative RT-PCR. To ensure that PCR amplification was in the linear range (or the exponential phase), using RT product from embryonic chicken pituitaries, we first examined the kinetics of PCR reaction to determine cycle numbers used in the following experiments (Figure 4Go). Based on the amplification kinetics, 23 cycles were chosen for ß-actin gene and 29 cycles for GR (Figure 4Go). As shown in Figure 5Go, GR is shown to be expressed at a relatively constant level during embryonic pituitary development (at E8, E12, E16, and E20; Figure 5Go).


Figure 4
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  		Figure 4. Validation of the semiquantitative reverse transcription PCR assay for chicken ß-actin gene (upper) and glucocorticoid receptor (GR) gene (lower). Kinetics of PCR amplification with the electrophoretic images is shown at the bottom. The cycle numbers (23 cycles for ß-actin and 29 cycles for GR), at which PCR amplification was performed in its linear range, were used to analyze the expression levels of genes in pituitary. Reverse transcription products from embryonic pituitaries were used as a template for PCR reactions.

 

Figure 5
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  		Figure 5. Expression profile of glucocorticoid receptor (GR) during embryonic pituitary development. The GR:ß-actin at E8 is used as a reference point, and GR expression level is represented as percentage of GR:ß-actin at E8. Each data point represents the mean ± SEM of at least 3 individual chicken embryos. The electrophoretic image is shown above the graph. E8, E12, E16 and E20 indicate pituitaries collected from embryonic d 8, 12, 16, and 20, respectively.

 
Interestingly, high expression level of GR was also observed in early chicken embryos (from embryonic d 2 to 5; Figure 6Go).


Figure 6
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  		Figure 6. Detection of glucocorticoid receptor (GR) mRNA in whole chicken embryos from embryonic d 2 (E2) to 5 (E5). Numbers in parentheses indicate the PCR cycle numbers used.

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
In the present study, we cloned the full-length cDNA for cGR and investigated its tissue distribution and expression profile during embryonic pituitary development. The results from our experiments demonstrated the expression of GR in the embryonic pituitaries, whole embryos at early developmental stages, and all adult tissues of chickens.

Alignment of GR amino acid sequences from different species shows that the cGR shares higher sequence identity with that of mammals, including the human (73%; Hollenberg et al., 1985), mouse (73%; Francke and Gehring, 1980), rat (71%; Miesfeld et al., 1986), rabbit (72%; James et al., 2003), and lower sequence identity with that of trout (51%; Gao et al., 1994), as shown in Figure 1Go. A phylogenetic tree with bootstrap values was constructed by MEGA 3.1 (Figure 1Go, panel B). Chicken GR is shown to be more closely related to that of mammalian species than that of fish.

The central DNA binding domain (amino acids 416 to 481) is conserved in cGR and shares 100% sequence identity to human GR (hGR), mouse GR (mGR), and rat GR. This includes 8 Cys residues critical for Zn finger formation and phenylalanine residues (amino acids 444 and 445 in hGR) critical for nuclear export (Black et al., 2001), which are shown to be conserved throughout members of the retinoic acid, thyroid, and steroid receptor superfamily (Lu and Cidlowski, 2005). The C-terminal ligand-binding domain of cGR also shares high homology to GR from other species (89% to hGR and rat GR; 90% to mGR), possibly due to their need to bind to a common ligand, the glucocorticoids. In contrast, the cGR N-terminal modulatory domain shows comparatively lower homology to that of the other species than the other functional domains (60% and 59% to hGR and mGR, respectively).

In the present study, we have not identified cGR isoforms by RT-PCR yet. However, GR isoforms are widely observed in other species (Hollenberg et al., 1985; Korn et al., 1998). In humans, alternative splicing of exon 9{alpha} and 9ß in GR yields 2 transcriptional isoforms: GR{alpha} and GRß (Lu and Cidlowski, 2005). To date, we have found no evidence of an alternative 9ß exon and thus no proof of ß-isoform in cGR. Alternative translation initiation due to mechanisms such as leaky ribosomal scanning are also shown to generate translational isoforms in GR from many mammalian species (Yudt and Cidlowski, 2001; Lu and Cidlowski, 2005). Alternative translation initiation sites, similar to that of hGR, are in cGR: Met 29, Met 88, Met 92, and Met 100, corresponding to Met 27, Met 86, Met 90, and Met 98, which generate GR-B, GR-C1, GR-C2, and GR-C3 isoforms in hGR, respectively (Lu and Cidlowski, 2005; Figure 1Go). Thus, we cannot rule out the possibility that chicken GR may also exist in multiple isoforms, because the differential expression of these variants may give rise to a tissue-specific population that determines unique biological responses in a particular tissue. Further investigations would be required to determine the presence of cGR isoforms, their functional difference, and corresponding roles in transduction of GC actions in chickens.

The importance of GR in metabolism and other important cellular functions is well documented in mammals (Rouleau et al., 1987; Darmaun et al., 1988; Lamounier-Zepter and Ehrhart-Bornstein, 2006). Concurring with previous studies on mammalian GR, our cGR is expressed in all adult tissues investigated. Though expressed in all tissues, the level of expression observed varies among different tissues. The GR is shown to be abundantly expressed in pituitary and kidney. They are both targets for the negative feedback mechanism of GC, because corticotrophs in the pituitary and adrenal cortex above the kidney enhance GC level indirectly by release of adrenocorticotropic hormone and directly, respectively. It explains the high expression level of GR for regulation on GC production in these 2 organs. Muscle and liver are also shown to have relatively high expression of GR. Elevated GC production due to stress regulates metabolism of proteins in muscle and carbohydrates in liver, thus adequate GR expression is required for transduction of GC actions for either proteolysis or gluconeogenesis. It is well demonstrated that GC affects reproduction in mammals; for instance, it helps to stimulate parturition in sheep (Challis et al., 2001).

Abundant GR expression was found in whole chicken embryos collected at embryonic d 2, 3, 4, and 5 (Figure 6Go). As the chicken pituitary appears to become fully separated from Rathke’s pouch only at embryonic d 7 to E8 (Sasaki et al., 2003), we speculate extrapituitary organs should be responsible for GR expression detected. Organs developed in the early embryonic stage (from embryonic d 2 to 5), such as the brain, are believed to be the major source of GR. Because GR expression appears much earlier than the detectable serum GC level, the physiological relevance of GR in earlier embryonic development remains to be clarified.

Glucocorticoid receptor expression was first detected in the chicken pituitary at E8 when it becomes fully separated, and it remains more or less constant during development (from E8 to E20). Somatotrophs are shown to first appear at embryonic d 14, whereas pituitary cells collected at E12 differentiate into somatotroph after treatment of corticosterone (Porter et al., 1995; Dean and Porter, 1999). Moreover, 3 d of GC exposure can also induce lactotroph differentiation in pituitaries from embryonic d 13 (Fu and Porter, 2004). From these findings, the responsiveness of somatotroph and lactotroph to glucocorticoids appears to be limited by expression of GR, which is supposed to increase during embryonic development and thus allow cells to become more sensitive to GC and affect biological responses. However, evidence from our present study and previous studies using western blotting with antibody against hGR (Bossis et al., 2004) showed abundant GR expression was first detected in chicken pituitary at E8, suggesting that expression of GR is not a limiting factor to GC responsiveness in pituitary cells collected before E12. Studies have shown a surge of MR expression coincides with somatotroph differentiation, and MR expression is only detected in growth hormone-containing cells nearly exclusively. Mineralocorticoid receptor is therefore suggested to be related to enhanced GC responsiveness in pituitary development (Bossis et al., 2004). Evidence has shown that GR and MR can form heterodimers with better capacity in DNA binding and transactivation than GR or MR homodimers (Trapp et al., 1994). However, the mechanism of how GR and MR act in concert to signal the onset of somatotroph and lactotroph differentiation in embryonic pituitary remains unclear.

In summary, a full-length cDNA coding for chicken GR has been successfully cloned in the present study. To our knowledge, this represents the first one in avian species. Reverse transcription PCR assay shows that GR is widely expressed in all tissues examined. Using semi-quantitative RT-PCR, we have further demonstrated that GR is abundantly expressed in embryonic pituitaries from E8 to E20, clearly suggesting that expression of GR is not a limiting factor in GC-induced differentiation of somatotroph and lactotroph in the embryonic pituitary of birds.


   ACKNOWLEDGMENTS
 
This work was supported by the Research Grants Council of the Hong Kong government, HKU7345/03M.

Received for publication May 1, 2006. Accepted for publication August 29, 2006.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Black, B. E., J. M. Holaska, F. Rastinejad, and B. M. Paschal. 2001. DNA binding domains in diverse nuclear receptors function as nuclear export signals. Curr. Biol. 11:1749–1758.[ISI][Medline]

Bossis, I., S. Nishimura, M. Muchow, and T. E. Porter. 2004. Pituitary expression of type I and type II glucocorticoid receptors during chicken embryonic development and their involvement in growth hormone cell differentiation. Endocrinology 145:3523–3531.[Abstract/Free Full Text]

Bossis, I., and T. E. Porter. 2003. Evaluation of glucocorticoid-induced growth hormone gene expression in chicken embryonic pituitary cells using a novel in situ mRNA quantitation method. Mol. Cell. Endocrinol. 201:13–23.[ISI][Medline]

Caelles, C., J. M. Gonzalez-Sancho, and A. Munoz. 1997. Nuclear hormone receptor antagonism with AP-1 by inhibition of the JNK pathway. Genes Dev. 11:3351–3364.[Abstract/Free Full Text]

Challis, J. R., D. Sloboda, S. G. Matthews, A. Holloway, N. Alfaidy, F. A. Patel, W. Whittle, M. Fraser, T. J. Moss, and J. Newnham. 2001. The fetal placental hypothalamic-pituitary-adrenal (HPA) axis, parturition and post natal health. Mol. Cell. Endocrinol. 185:135–144.[ISI][Medline]

Darmaun, D., D. E. Matthews, and D. M. Bier. 1988. Physiological hypercortisolemia increases proteolysis, glutamine, and alanine production. Am. J. Physiol. 255:E366–E373.

Dean, C. E., and T. E. Porter. 1999. Regulation of somatotroph differentiation and growth hormone (GH) secretion by corticosterone and GH-releasing hormone during embryonic development. Endocrinology 140:1104–1110.[Abstract/Free Full Text]

Dieken, E. S., and R. L. Miesfeld. 1992. Transcriptional transactivation functions localized to the glucocorticoid receptor N terminus are necessary for steroid induction of lymphocyte apoptosis. Mol. Cell. Biol. 12:589–597.[Abstract/Free Full Text]

Francke, U., and U. Gehring. 1980. Chromosome assignment of a murine glucocorticoid receptor gene (Grl-1) using intra-species somatic cell hybrids. Cell 22:657–664.[ISI][Medline]

Fu, X., and T. E. Porter. 2004. Glucocorticoid induction of lactotrophs and prolactin gene expression in chicken embryonic pituitary cells: A delayed response relative to stimulated growth hormone production. Endocrinology 145:1322–1330.[Abstract/Free Full Text]

Gao, X., E. Kalkhoven, J. Peterson-Maduro, B. van der Burg, and O. H. Destree. 1994. Expression of the glucocorticoid receptor gene is regulated during early embryogenesis of Xenopus laevis. Biochim. Biophys. Acta 1218:194–198.[Medline]

Giguere, V., S. M. Hollenberg, M. G. Rosenfeld, and R. M. Evans. 1986. Functional domains of the human glucocorticoid receptor. Cell 46:645–652.[ISI][Medline]

Hirasawa, N., Y. Sato, Y. Fujita, S. Mue, and K. Ohuchi. 1998. Inhibition by dexamethasone of antigen-induced c-Jun N-terminal kinase activation in rat basophilic leukemia cells. J. Immunol. 161:4939–4943.[Abstract/Free Full Text]

Hollenberg, S. M., C. Weinberger, E. S. Ong, G. Cerelli, A. Oro, R. Lebo, E. B. Thompson, M. G. Rosenfeld, and R. M. Evans. 1985. Primary structure and expression of a functional human glucocorticoid receptor cDNA. Nature 318:635–641.[Medline]

James, E. R., L. Robertson, E. Ehlert, P. Fitzgerald, N. Droin, and D. R. Green. 2003. Presence of a transcriptionally active glucocorticoid receptor a in lens epithelial cells. Invest. Ophthalmol. Vis. Sci. 44:5269–5276.[Abstract/Free Full Text]

Korn, S. H., E. Koerts-de Lang, G. E. Engel, J. W. Arends, E. F. Wouters, and F. B. Thunnissen. 1998. {alpha} and ß Glucocorticoid receptor mRNA expression in skeletal muscle. J. Muscle Res. Cell Motil. 19:757–765.[ISI][Medline]

Kumar, R., and E. B. Thompson. 2005. Gene regulation by the glucocorticoid receptor: Structure:function relationship. J. Steroid Biochem. Mol. Biol. 94:383–394.[ISI][Medline]

Lamounier-Zepter, V., and M. Ehrhart-Bornstein. 2006. Fat tissue metabolism and adrenal steroid secretion. Curr. Hypertens. Rep. 8:30–34.[ISI][Medline]

Lu, N. Z., and J. A. Cidlowski. 2005. Translational regulatory mechanisms generate N-terminal glucocorticoid receptor isoforms with unique transcriptional target genes. Mol. Cell 18:331–342.[ISI][Medline]

Mangelsdorf, D. J., C. Thummel, M. Beato, P. Herrlich, G. Schutz, K. Umesono, B. Blumberg, P. Kastner, M. Mark, P. Chambon, and R. M. Evans. 1995. The nuclear receptor superfamily: The second decade. Cell 83:835–839.[ISI][Medline]

McKay, L. I., and J. A. Cidlowski. 2000. CBP (CREB binding protein) integrates NF-{kappa}B (nuclear factor-{kappa}B) and glucocorticoid receptor physical interactions and antagonism. Mol. Endocrinol. 14:1222–1234.[Abstract/Free Full Text]

Miesfeld, R., S. Rusconi, P. J. Godowski, B. A. Maler, S. Okret, A. C. Wikstrom, J. A. Gustafsson, and K. R. Yamamoto. 1986. Genetic complementation of a glucocorticoid receptor deficiency by expression of cloned receptor cDNA. Cell 46:389–399.[ISI][Medline]

Miller, T. L., and K. E. Mayo. 1997. Glucocorticoids regulate pituitary growth hormone-releasing hormone receptor messenger ribonucleic acid expression. Endocrinology 138:2458–2465.[Abstract/Free Full Text]

Nogami, H., Y. Hiraoka, K. Ogasawara, S. Aiso, and S. Hisano. 2005. The role of pit-1 in the regulation of the rat growth hormone-releasing hormone receptor gene transcription by glucocorticoids. J. Mol. Endocrinol. 35:477–488.[Abstract/Free Full Text]

Nogami, H., K. Inoue, and K. Kawamura. 1997. Involvement of glucocorticoid-induced factor(s) in the stimulation of growth hormone expression in the fetal rat pituitary gland in vitro. Endocrinology 138:1810–1815.[Abstract/Free Full Text]

Nogami, H., K. Inoue, H. Moriya, A. Ishida, S. Kobayashi, S. Hisano, M. Katayama, and K. Kawamura. 1999. Regulation of growth hormone-releasing hormone receptor messenger ribonucleic acid expression by glucocorticoids in MtT-S cells and in the pituitary gland of fetal rats. Endocrinology 140:2763–2770.[Abstract/Free Full Text]

Nogami, H., and T. Tachibana. 1993. Dexamethasone induces advanced growth hormone expression in the fetal rat pituitary gland in vivo. Endocrinology 132:517–523.[Abstract]

Porter, T. E. 2005. Regulation of pituitary somatotroph differentiation by hormones of peripheral endocrine glands. Domest. Anim. Endocrinol. 29:52–62.[ISI][Medline]

Porter, T. E., G. S. Couger, C. E. Dean, and B. M. Hargis. 1995. Ontogeny of growth hormone (GH)-secreting cells during chicken embryonic development: Initial somatotrophs are responsive to GH-releasing hormone. Endocrinology 136:1850–1856.[Abstract]

Porter, T. E., L. E. Ellestad, A. Fay, J. L. Stewart, and I. Bossis. 2006. Identification of the chicken growth hormone-releasing hormone receptor (GHRH-R) mRNA and gene: Regulation of anterior pituitary GHRH-R mRNA levels by homologous and heterologous hormones. Endocrinology 147:2535–2543.[Abstract/Free Full Text]

Rouleau, G., G. Karpati, S. Carpenter, M. Soza, S. Prescott, and P. Holland. 1987. Glucocorticoid excess induces preferential depletion of myosin in denervated skeletal muscle fibers. Muscle Nerve 10:428–438.[ISI][Medline]

Sasaki, F., A. Doshita, Y. Matsumoto, S. Kuwahara, Y. Tsukamoto, and K. Ogawa. 2003. Embryonic development of the pituitary gland in the chick. Cells Tissues Organs 173:65–74.[ISI][Medline]

Schule, R., P. Rangarajan, S. Kliewer, L. J. Ransone, J. Bolado, N. Yang, I. M. Verma, and R. M. Evans. 1990. Functional antagonism between oncoprotein c-Jun and the glucocorticoid receptor. Cell 62:1217–1226.[ISI][Medline]

Senaris, R. M., F. Lago, R. Coya, J. Pineda, and C. Dieguez. 1996. Regulation of hypothalamic somatostatin, growth hormone-releasing hormone, and growth hormone receptor messenger ribonucleic acid by glucocorticoids. Endocrinology 137:5236–5241.[Abstract]

Song, C. Z., X. Tian, and T. D. Gelehrter. 1999. Glucocorticoid receptor inhibits transforming growth factor-ß signaling by directly targeting the transcriptional activation function of Smad3. Proc. Natl. Acad. Sci. USA 96:11776–11781.[Abstract/Free Full Text]

Stocklin, E., M. Wissler, F. Gouilleux, and B. Groner. 1996. Functional interactions between Stat5 and the glucocorticoid receptor. Nature 383:726–728.[Medline]

Tang, Y., R. H. Getzenberg, B. N. Vietmeier, M. R. Stallcup, M. Eggert, R. Renkawitz, and D. B. DeFranco. 1998. The DNA-binding and tau2 transactivation domains of the rat glucocorticoid receptor constitute a nuclear matrix-targeting signal. Mol. Endocrinol. 12:1420–1431.[Abstract/Free Full Text]

Trapp, T., R. Rupprecht, M. Castren, J. M. Reul, and F. Holsboer. 1994. Heterodimerization between mineralocorticoid and glucocorticoid receptor: A new principle of glucocorticoid action in the CNS. Neuron 13:1457–1462.[ISI][Medline]

Wang, Y., and W. Ge. 2003. Involvement of cyclic adenosine 3',5'-monophosphate in the differential regulation of activin ß A and ß B expression by gonadotropin in the zebrafish ovarian follicle cells. Endocrinology 144:491–499.[Abstract/Free Full Text]

Wang, Y., and W. Ge. 2004. Developmental profiles of activin ß A, ß B, and follistatin expression in the zebrafish ovary: Evidence for their differential roles during sexual maturation and ovulatory cycle. Biol. Reprod. 71:2056–2064.[Abstract/Free Full Text]

Wang, C. Y., Y. Wang, J. Li, and F. C. Leung. 2006. Expression profiles of growth hormone-releasing hormone and growth hormone-releasing hormone receptor during chicken embryonic pituitary development. Poult. Sci. 85:569–576.[Abstract/Free Full Text]

Wang, Y., A. O. Wong, and W. Ge. 2003. Cloning, regulation of messenger ribonucleic acid expression, and function of a new isoform of pituitary adenylate cyclase-activating polypeptide in the zebrafish ovary. Endocrinology 144:4799–4810.[Abstract/Free Full Text]

Yudt, M. R., and J. A. Cidlowski. 2001. Molecular identification and characterization of a and b forms of the glucocorticoid receptor. Mol. Endocrinol. 15:1093–1103.[Abstract/Free Full Text]

Zhang, Z., S. Jones, J. S. Hagood, N. L. Fuentes, and G. M. Fuller. 1997. STAT3 acts as a co-activator of glucocorticoid receptor signaling. J. Biol. Chem. 272:30607–30610.[Abstract/Free Full Text]





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