Identification of target cells for growth hormone's action in the arcuate nucleus

Burton, Kimberly A.; Kabigting, E B; Steiner, Robert A.; Clifton, Donald K.

doi:10.1152/ajpendo.1995.269.4.e716

Cited by 27 publications

(23 citation statements)

References 19 publications

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“…Nevertheless, recent data indicate that the GH receptor gene is expressed in the rat hypothalamus , and GH receptor mRNA-containing cells have been visualized in the PeV and the ARC, the major respective locations of SRIH and GHRH neurons (Burton et al, 1992;Minami et al, 1993;Burton et al, 1995). A comparable distribution has also been reported on the basis of immunohistochemical studies (Lobie et al, 1993).…”

Section: Abstract: Antisense Oligonucleotides; Growth Hormone Receptmentioning

confidence: 75%

“…In a similar protocol, V1 receptor mRNA levels were also markedly increased locally after intraseptal infusion of AS oligonucleotides when compared with those of vehicle-or scrambled sequence-infused animals, and this resulted in a 60% decrease in V1 receptor binding (Landgraf et al, 1995). The effect of intracerebroventricular AS infusion on GH receptor mRNA levels was significantly more marked in the PeV than in the ARC, two major sites of rGH-R expression in the hypothalamus (Burton et al, 1992;Minami et al, 1993;Burton et al, 1995). We cannot exclude the possibility that diffusion of the ODN from the ventricle to the ARC is different than to the PeV, because of the presence of specialized ependymocytes such as the tanycytes.…”

Section: Discussionmentioning

confidence: 92%

“…GHRH neurons in the ARC have not yet been convincingly reported as expressing GH receptor gene transcripts, in contrast to the majority of arcuate NPY-containing neurons (Chan et al, 1995;Burton et al, 1995). Moreover, in hypophysectomized rats, 60 min after an intravenous injection of GH, expression of the c-fos gene is increased in arcuate NPY but not in GHRH neurons (Kamegai et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

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Central Administration of a Growth Hormone (GH) Receptor mRNA Antisense Increases GH Pulsatility and Decreases Hypothalamic Somatostatin Expression in Rats

et al. 1996

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To test the hypothesis of the involvement of centrally expressed rat growth hormone receptors (rGH-R) in the ultradian rhythmicity of pituitary GH secretion, adult male rats were submitted to a 60 hr intracerebroventricular infusion of an antisense (AS) oligodeoxynucleotide (ODN) complementary to the sequence of rGH-R mRNA. Eight hour (10 A.M.-6 P.M.) GH secretory profiles, obtained from freely moving male rats infused with 2.0 nmol/hr of rGH-R AS, revealed a marked increase in GH peak amplitude (150 +/- 12 vs 101 +/- 10 ng/ml), trough levels (16.2 +/- 3.0 vs 5.4 +/- 1.4 ng/ml), and number of peaks (2.9 +/- 0.3 vs 1.8 +/- 0.2). No change was observed in rats treated with an ODN complementary to the prolactin receptor mRNA sequence (2.0 nmol/hr). Infusion of increasing ODN concentrations resulted in a dose-dependent stimulation of GH release. In parallel, somatogenic binding sites in the choroid plexus were decreased by 40%, and levels of rGH-R mRNA were increased in the periventricular nucleus (PeV) but unchanged in the arcuate nucleus (ARC). Levels of somatostatin mRNA, in the PeV but not in the ARC, were lowered by the treatment. Levels of GH-releasing hormone mRNA in the ARC were not affected. These data suggest that GH negative feedback results from a direct effect on central GH receptors and a subsequent activation of hypophysiotropic somatostatin neurons located in the anterior periventricular hypothalamus.

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Section: Abstract: Antisense Oligonucleotides; Growth Hormone Receptmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

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Central Administration of a Growth Hormone (GH) Receptor mRNA Antisense Increases GH Pulsatility and Decreases Hypothalamic Somatostatin Expression in Rats

et al. 1996

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“…The actions of GH would necessarily be mediated by GH receptor signaling. In the rat hypothalamus, GH receptors have been localized to PeN SRIH neurons [35], and neuropeptide Y (NPY)-containing neurons, but only minimally on GHRH neurons in the arcuate nucleus [7, 36]. It is likely that GH receptors are present on the same neuronal types in the mouse hypothalamus.…”

Section: Discussionmentioning

confidence: 99%

Growth Hormone Releasing Hormone Expression During Postnatal Development in Growth Hormone-Deficient Ames Dwarf Mice:mRNA in situ Hybridization

1998

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Several genetic mutations in mice and rats that produce lifelong growth hormone (GH) deficiency result in overexpression of GH-releasing hormone (GHRH) mRNA in hypothalamic arcuate nucleus neurons. In order to examine the development of this condition, GHRH mRNA expression was quantified in Ames dwarf (df/df) and normal (DF/?) mice at 1 (day of birth), 3, 7, 14, 21 and 60 postnatal days (d) following in situ hybridization. Total mRNA was assessed using computer-assisted densitometry after X-ray film autoradiography, and mRNA expression per neuron was quantified by counts of grains per cell after emulsion autoradiography. Total GHRH mRNA was the same in dwarf and normal mice at 1, 3 and 7d. GHRH mRNA in dwarfs increased at 14d to 240% of that in DF/? (p < 0.005); the percentage overexpression in dwarf mice remained ≧200% through 60d, although total GHRH mRNA increased in both dwarfs and normals during this period. GHRH mRNA per neuron was the same in normal and dwarf mice at 1d, then increased in dwarfs to 190% of that in normals at 3d (p < 0.05), and rose to 300% of normal levels by 7d and beyond (p < 0.005). There was no sexual dimorphism in expression by either measure in normal or dwarf mice. These results indicate that an increase in GHRH mRNA in Ames dwarf mice is first detectable at 3d, a period of approximately 7d after the failure to initiate GH production, which occurs normally at embryonic day 17.5. The onset of GHRH overexpression occurs earlier than the decline of either hypophysiotropic somatostatin or dopamine in Ames dwarf mice. This difference may be due to the stimulatory action of GHRH, as opposed to the inhibitory effects of factors examined previously.

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“…To determine whether c-fos might be involved in the response of central neurones to GH, we have used both single-and double-label in situ hybridization to study the effect of GH administration on c-fos mRNA in hypothalamic neurones [8], We found that GH induces c-fos expression in the ARC, suggesting that immediate early gene expression plays a role in transduc ing feedback action of GH on the brain. However, although c-yb.s-expressing neurones in the medial ARC are abundant, few, if any, of these are either GHRH or soma tostatin neurones.…”

Section: Growth Hormone-dependent Feedbackmentioning

confidence: 99%

Role of NPY Neurones in GH-Dependent Feedback Signalling to the Brain

Chan¹,

Clifton²,

Steiner³

1996

Horm Res

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The neuroendocrine regulation of pulsatile growth hormone (GH) secretion involves the reciprocal interactions between growth hormone-releasing hormone (GHRH)- and somatostatin-containing neurones, residing primarily in the hypothalamic arcuate nucleus (ARC) and the periventricular nucleus (PeN), respectively. Considerable evidence supports the concept that GH itself participates in the regulation of its own rhythmic secretion through a reciprocal feedback on GHRH and somatostatin neurones. The direct actions of GH are mediated through GH receptors, and in the PeN, the majority of somatostatin neurones express this receptor. GH induces the expression of the immediate early gene c-fos in the ARC; however, few GHRH residing in the ARC express the GH receptor, suggesting that the action of GH on GHRH cells must be indirect through another population of unidentified cells. NPY neurones express c-fos in response to GH, and preliminary results suggest that NPY neurones in the ARC express the GH receptor. These observations suggest that NPY neurones play a physiological role in the feedback of regulation of GH secretion.

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Identification of target cells for growth hormone's action in the arcuate nucleus

Cited by 27 publications

References 19 publications

Central Administration of a Growth Hormone (GH) Receptor mRNA Antisense Increases GH Pulsatility and Decreases Hypothalamic Somatostatin Expression in Rats

Central Administration of a Growth Hormone (GH) Receptor mRNA Antisense Increases GH Pulsatility and Decreases Hypothalamic Somatostatin Expression in Rats

Growth Hormone Releasing Hormone Expression During Postnatal Development in Growth Hormone-Deficient Ames Dwarf Mice:mRNA in situ Hybridization

Role of NPY Neurones in GH-Dependent Feedback Signalling to the Brain

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