The Growth Hormone (GH) Gene Is Expressed in the Lateral Hypothalamus: Enhancement by GH-Releasing Hormone and Repression by Restraint Stress

Yoshizato, Hideo; Fujikawa, Takahiko; Soya, Hideaki; Tanaka, Minoru; Nakashima, Kenichiro

doi:10.1210/endo.139.5.6009

Cited by 46 publications

(13 citation statements)

References 36 publications

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“…hCS-A expression was detectable at trace levels in brain, testis, ovary, and kidney. Recent studies have reported low levels of GH gene expression in the rat brain (38) and GH and CS gene expression in human testis (39) and ovary (40). These observations suggest that the low level "ectopic" expression from the hGH/P1 transgene that we have observed may instead reflect normal physiologic patterns of low level gene expression.…”

Section: Discussionmentioning

confidence: 43%

The Human Growth Hormone Gene Cluster Locus Control Region Supports Position-independent Pituitary- and Placenta-specific Expression in the Transgenic Mouse

Su¹,

Liebhaber²,

Cooke³

2000

Journal of Biological Chemistry

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The human growth hormone (hGH) cluster contains five genes. The hGH-N gene is predominantly expressed in pituitary somatotropes, whereas the remaining four genes, the chorionic somatomammotropin genes (hCS-L, hCS-A, and hCS-B) and hGH-V, are expressed selectively in the placenta. In contrast, the mouse genome contains a single pituitary-specific GH gene and lacks any GHrelated CS genes. Activation of the hGH transgene in the mouse is dependent on its linkage to a previously described locus control region (LCR) located ؊15 to ؊32 kilobases upstream of the hGH cluster. The sporadic, nonreproducible expression of hCS transgenes lacking the LCR suggests that they may be dependent on hGH LCR activity as well. To determine whether the hCS genes could be expressed with appropriate placental specificity, a series of five transgenic mouse lines carrying an 87-kilobase human genomic insert encompassing the majority of the hGH gene cluster and the entire contiguous LCR was established. All of the hGH cluster genes were appropriately expressed in each of these lines. High level expression of hGH was restricted to the pituitary and hCS to the labyrinthine layer of the placenta. The expression of the GH cluster genes in their respective tissues paralleled transgene copy numbers irrespective of the transgene insertion site in the host mouse genome. These studies have extended the utility of the transgenic mouse model for the analysis of the full spectrum of hGH gene cluster activation. Further, they support a role for the hGH LCR in placental hCS, as well as pituitary hGH gene activation, and expression.

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Section: Discussionmentioning

confidence: 43%

The Human Growth Hormone Gene Cluster Locus Control Region Supports Position-independent Pituitary- and Placenta-specific Expression in the Transgenic Mouse

Su¹,

Liebhaber²,

Cooke³

2000

Journal of Biological Chemistry

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“…IGF-IA, IB and -actin mRNA expressions were detected by reverse transcription-polymerase chain reaction (RT-PCR)/Southern blot hybridization as described previously [9]. The primer pairs used for PCR of IGF-I cDNA can detect IGF-IA and IB at the same time and as different length of fragments (Fig.…”

Section: Methodsmentioning

confidence: 99%

20kDa Human Growth Hormone (20K hGH) Stimulates Insulin-Like Growth Factor-I (IGF-I) Gene Expression at Lower Concentrations than 22K hGH in hGH Receptor-Expressing Ba/F3 Cells

et al. 2000

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Abstract.Growth hormone (GH) secreted from the pituitary is essential for postnatal growth in animals. GH exerts its actions by a direct effect on target organs and by stimulating insulin-like growth factor I (IGF-I) production. In the human pituitary, there is a naturally occurring variant protein which has a molecular mass of 20 kDa (20K hGH) besides the major 22 kDa hGH (22K hGH), but the physiological actions of 20K hGH are still poorly understood. In this study we have examined its effects on the IGF-I mRNA expression in the pro B-cell line Ba/F3 cells stably expressing hGH receptor (Ba/F3-hGHR).Ba/F3-hGHR cells were incubated for 2 h with a series of various concentrations (10 pM^ 10 nM) of 20K or 22K hGH. The IGF-I mRNA expression in the Ba/F3-hGHR cells was detected by the RT-PCR method.IGF-I gene expression was increased by 20K and 22K hGH stimulation, but not by PRL or IL-3 in the Ba/F3-hGHR.And this effect was not observed in parental Ba/F3 cells. Lower concentrations of 20K hGH more strongly induced IGF-I gene expression than 22K-hGH.These results suggest that 20K and 22K hGH stimulate the IGF-I gene expression in the Ba/F3-hGHR through hGH receptors, and that the stronger effect of 20K hGH than that of 22K hGH in enhancing the IGF-I gene expression may be correlated with a 20K hGH specific receptor dimerization mechanism. GROWTH hormone (GH) exerts its growth promoting actions mainly by stimulating insulin-like growth factor I (IGF-I) production. In liver and skeletal muscle, IGF-I mRNA expression is known to be regulated by GH through the GH receptor (GHR) [1][2][3]. In the human pituitary gland and plasma, there is a naturally occurring variant GH protein whose molecular mass is 20 kDa (20K hGH) besides the major 22 kDa hGH (22K hGH) [4]. The 20K hGH lacks the amino acid residues 32 to 46 of 22K hGH and derives from the same gene (hGH-N) as 22K hGH by alternative mRNA splicing. 20K hGH has also been documented to possess full growthpromoting activity and somatomedin-generating potency as in 22K hGH via GHR in vivo [4, 5]. It also shows the same affinity for hGHR [6], although these two hGH isoforms have differences in clearance rates [7], and in the formation of GHR dimers and binding to GH binding protein [8]. But other physiological actions of 20K-hGH, especially the IGF-I mRNA expression which is one of the major effect of GH, are still poorly understood. In this study we have examined their effects on IGF-I mRNA expression in the pro B-cell line, Ba/F3 cells, stably expressing hGH receptor (Ba/F3-hGHR), and have found evidence that 20K hGH is more potent than 22K hGH in inducing IGF-I mRNA expression.

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“…Species GH GH mRNA Neural Tissues brain human Kyle et al 1981rat Pacold et al 1978Lechan et al 1981Hojvat et al 1982a, b Gossard et al 1987Martinoli et al 1991Yoshizato et al 1998chicken Render et al 1995bRender et al 1995bfrog Yon et al 1991 Lechan et al 1981 Reproductive tissues testis human Untergasser et al 1997, 1998aUntergasser et al 1996, 1998achicken Hull et al 1999 Mol et al 1995bMol et al 1995bdog Eigenmenn et al 1983Mol et al 1995a, 1996Van Garderen et al 1997Selman et al 1991, 1994a, b Mol et al 1995acat Watson et al 1987Mol et al 1995a Lymphoid tissues thymus human Wu et al 1996Sabharwal and Varma 1996Wu et al 1996 rat Binder et al 1994thymic epithelia human Maggiano et al 1994de Mello-Coelho et al 1998Maggiano et al 1994;Wu et al 1996 Varma et al 1993Malarkey et al 1996rat Weigent et al 1988Baxter et al 1991aWeigent et al 1992 human Kao et al 1992b…”

Section: Tissuementioning

confidence: 99%

“…The release of GH from amygdaloid, hippocampal, and hypothalamic cells in vitro is, however, suppressed by SRIF, as is the release of pituitary GH (Pacold et al 1978;Hojvat et al 1982b). However, while restraint stress represses GH gene expression in the rat lateral hypothalamus, it has no effect on pituitary GH mRNA (Yoshizato et al 1998). The turnover of GH mRNA in the rat hypothalamus also appears to be more rapid than in pituitary tissue (Yoshizato et al 1998), and the increase in hypothalamic GH mRNA induced by GHRH is far greater than the GHRH-induced increase in pituitary GH mRNA (Yoshizato et al 1998).…”

Section: Extrapituitary Gh: Tissue-specific Synthesismentioning

confidence: 99%

Pituitary and extrapituitary growth hormone: Pit-1 dependence?

Harvey

Azumaya²,

Hull³

2000

Can. J. Physiol. Pharmacol.

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Growth hormone (GH) is primarily produced in pituitary somatotrophs. The synthesis of this hormone is thought to be dependent upon a pituitary-specific transcription factor (Pit-1). However, many extrapituitary tissues are now known to express GH genes. The extrapituitary production of GH may therefore indicate an extrapituitary distribution of the Pit-1 gene. The extrapituitary production of GH may, alternatively, indicate that GH expression occurs independently of Pit-1 in extrapituitary tissues. These possibilities are considered in this brief review.

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The Growth Hormone (GH) Gene Is Expressed in the Lateral Hypothalamus: Enhancement by GH-Releasing Hormone and Repression by Restraint Stress

Cited by 46 publications

References 36 publications

The Human Growth Hormone Gene Cluster Locus Control Region Supports Position-independent Pituitary- and Placenta-specific Expression in the Transgenic Mouse

The Human Growth Hormone Gene Cluster Locus Control Region Supports Position-independent Pituitary- and Placenta-specific Expression in the Transgenic Mouse

20kDa Human Growth Hormone (20K hGH) Stimulates Insulin-Like Growth Factor-I (IGF-I) Gene Expression at Lower Concentrations than 22K hGH in hGH Receptor-Expressing Ba/F3 Cells

Pituitary and extrapituitary growth hormone: Pit-1 dependence?

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