Pituitary Growth Hormone-Releasing Factor Receptor Expression in Normal and Dwarf Rats

Carmignac, Danielle; Flavell, David M.; Robinson, I. C. A. F.

doi:10.1159/000127116

Cited by 17 publications

(15 citation statements)

References 44 publications

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“…A shorter (␣) and a longer (␤) subtype of the short isoform have been distinguished; both are functional when expressed in host cells (Zeitler et al, 1998). Significant decreases in the levels of GHRH-R mRNA were reported previously in the pituitary of dw/dw rats (Carmignac et al, 1996;Zeitler et al, 1998), and the current results confirmed these observations. Findings in our laboratory suggest that GHRH binding is almost Figure 3.…”

Section: Discussionsupporting

confidence: 89%

“…In adult dwarf (dw/dw) rats, plasma concentration of GH, GH content of the pituitary, and GH and cAMP responses to GHRH are greatly decreased (Charlton et al, 1988;Carmignac and Robinson, 1990;Downs and Frohman, 1991). GHRH receptor (GHRH-R) mRNA levels are reduced in the pituitary of dw/dw rats (Carmignac et al, 1996;Zeitler et al, 1998). The signal transduction pathway might also be affected distal to the receptor protein (Brain et al, 1991;Downs and Frohman, 1991).…”

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confidence: 99%

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Deficiency of Growth Hormone-Releasing Hormone Signaling Is Associated with Sleep Alterations in the Dwarf Rat

et al. 2001

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The somatotropic axis, and particularly growth hormonereleasing hormone (GHRH), is implicated in the regulation of sleep-wake activity. To evaluate sleep in chronic somatotropic deficiency, sleep-wake activity was studied in dwarf (dw/dw) rats that are known to have a defective GHRH signaling mechanism in the pituitary and in normal Lewis rats, the parental strain of the dw/dw rats. In addition, expression of GHRH receptor (GHRH-R) mRNA in the hypothalamus/preoptic region and in the pituitary was also determined by means of reverse transcription-PCR, and GHRH content of the hypothalamus was measured. Hypothalamic/preoptic and pituitary GHRH-R mRNA levels were decreased in the dw/dw rats, indicating deficits in the central GHRHergic transmission. Hypothalamic GHRH content in dw/dw rats was also less than that found in Lewis rats. The dw/dw rats had less spontaneous nonrapid eye movement sleep (NREMS) (light and dark period) and rapid eye movement sleep (REMS) (light period) than did the control Lewis rats. After 4 hr of sleep deprivation, rebound increases in NREMS and REMS were normal in the dw/dw rat. As determined by fast Fourier analysis of the electroencephalogram (EEG), the sleep deprivation-induced enhancements in EEG slow-wave activity in the dw/dw rats were only one-half of the response in the Lewis rats. The results are compared with sleep findings previously obtained in GHRH-deficient transgenic mice. The alterations in NREMS are attributed to the defect in GHRH signaling, whereas the decreases in REMS might result from the growth hormone deficiency in the dw/dw rat.

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Section: Discussionsupporting

confidence: 89%

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confidence: 99%

Deficiency of Growth Hormone-Releasing Hormone Signaling Is Associated with Sleep Alterations in the Dwarf Rat

et al. 2001

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“…The quantity of the smaller of the two products ranged from 20 to 40% of the larger product based on ethidium bromide staining. Except for a decrease in the amount of product obtained from amplification of dw pituitary RNA, as recently reported (Carmignac et al 1996), there were no gross differences in the amplification products between the normal and dw pituitaries ( Fig. 1; lane 1 vs lane 2).…”

Section: Resultssupporting

confidence: 81%

Functional GHRH receptor carboxyl terminal isoforms in normal and dwarf (dw) rats

Zeitler

Stevens²,

Siriwardana³

1998

Journal of Molecular Endocrinology

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GHRH plays a critical role in pituitary somatotroph development and function, actions which are mediated by a G-protein coupled receptor (GHRHr) that has been recently cloned. PCR amplification of rat pituitary mRNA using primers that span the GHRHr coding region resulted in two distinct products. When sequenced, the two isoforms were identical through bp 1278 of the GHRH coding region. However, the novel variant, which we have termed GHRHr , contains a 131 bp deletion (1279-1408) and resumes at bp 1409 in the 3 UTR of the previously identified transcript (GHRHr ). The identical isoforms were present in pituitaries from dwarf (dw) rats. The predicted amino acid sequence for the alternate receptor isoform differs from the published amino acid sequence at the extreme carboxyl terminus, with the last 5 amino acids of the published sequence replaced and an additional 17 amino acids added to the sequence. When translated in vitro or expressed as an epitope-tagged construct in non-GHRHr containing cell lines, the GHRHr mRNA produces a 42 kDa protein product, appropriately larger than the 40 kDa product of GHRHr mRNA. Furthermore, GHRHr retains the ability to promote cAMP generation in response to GHRH when expressed in non-GHRHr containing cell lines. These results indicate the presence of a splice variant of rat GHRHr mRNA present in normal and dw rat pituitary that codes for a functional receptor protein with an alternate carboxyl terminal domain. These findings raise the possibilities of target cell regulation of GHRH response, modulation of response through receptor isoform interactions and the involvement of multiple intracellular signaling pathways.

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“…Previous studies have described that GHRH receptors are restrictively expressed in GH cells (27)(28)(29), although we cannot exclude the possibility that low levels of receptor may be present in some other pituitary cell types. If GHRH receptors are completely restricted to GH cells, then local alterations in flow are most likely a consequence of secretory activity from stimulated GH cells.…”

Section: Discussionmentioning

confidence: 82%

Cellular in vivo imaging reveals coordinated regulation of pituitary microcirculation and GH cell network function

Lafont

Desarménien

Cassou

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Growth hormone (GH) exerts its actions via coordinated pulsatile secretion from a GH cell network into the bloodstream. Practically nothing is known about how the network receives its inputs in vivo and releases hormones into pituitary capillaries to shape GH pulses. Here we have developed in vivo approaches to measure local blood flow, oxygen partial pressure, and cell activity at single-cell resolution in mouse pituitary glands in situ. When secretagogue (GHRH) distribution was modeled with fluorescent markers injected into either the bloodstream or the nearby intercapillary space, a restricted distribution gradient evolved within the pituitary parenchyma. Injection of GHRH led to stimulation of both GH cell network activities and GH secretion, which was temporally associated with increases in blood flow rates and oxygen supply by capillaries, as well as oxygen consumption. Moreover, we observed a time-limiting step for hormone output at the perivascular level; macromolecules injected into the extracellular parenchyma moved rapidly to the perivascular space, but were then cleared more slowly in a size-dependent manner into capillary blood. Our findings suggest that GH pulse generation is not simply a GH cell network response, but is shaped by a tissue microenvironment context involving a functional association between the GH cell network activity and fluid microcirculation.blood flow | hormone pulsatility | oxygen pressure | tissue microenvironment | extracellular space

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Pituitary Growth Hormone-Releasing Factor Receptor Expression in Normal and Dwarf Rats

Cited by 17 publications

References 44 publications

Deficiency of Growth Hormone-Releasing Hormone Signaling Is Associated with Sleep Alterations in the Dwarf Rat

Deficiency of Growth Hormone-Releasing Hormone Signaling Is Associated with Sleep Alterations in the Dwarf Rat

Functional GHRH receptor carboxyl terminal isoforms in normal and dwarf (dw) rats

Cellular in vivo imaging reveals coordinated regulation of pituitary microcirculation and GH cell network function

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