Quantitative Aspects of Growth Hormone Cell Maturation in the Normal and Little Mutant Mouse

Wilson, Doris B.; Wyatt, Darlene P.; Gadler, Richard M.; Baker, C. Bruce

doi:10.1159/000146504

Cited by 22 publications

(3 citation statements)

References 6 publications

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“…injection of naked DNA. This led to a highly significant body weight increase in an animal model in which an inherited growth defect appears to resemble human isolated GH deficiency type IB 14, 17, 28, 40. We are planning a similar study in immunocompetent dwarf mice (lit/lit), by injecting mouse GH DNA.…”

Section: Discussionmentioning

confidence: 99%

Germ cell tumors in patients infected by the human immunodeficiency virus

Fizazi

Amato

Beuzeboc

et al. 2001

Cancer

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A novel approach for the fabrication of multifunctional microspheres integrating several advantages of mesoporous, luminescence, and temperature responses into one single entity is reported. First, the hollow mesoporous silica capsules are fabricated via a sacrificial template route. Then, Gd2O3:Eu3+ luminescent nanoparticles are incorporated into the internal cavities to form rattle‐type mesoporous silica nanocapsules by an incipient‐wetness impregnation method. Finally, the rattle‐type capsules serve as a nanoreactor for successfully filling temperature‐responsive hydrogel via photoinduced polymerization to form the multifunctional composite microspheres. The organic–inorganic hybrid microspheres show a red emission under UV irradiation due to the luminescent Gd2O3:Eu3+ core. The in vitro cytotoxicity tests show that the samples have good biocompatibility, which indicates that the nanocomposite could be a promising candidate for drug delivery. In addition, flow cytometry and confocal laser scanning microscopy (CLSM) confirm that the sample can be effectively taken up by SKOV3 cells. For in vitro magnetic resonance imaging (MRI), the sample shows the promising spin‐lattice relaxation time (T1) weighted effect and could potentially apply as a T1‐positive contrast agent. This composite drug delivery system (DDS) provides a positive temperature controlled “on‐off”drug release pattern and the drug, indomethacin (IMC), is released fast at 45 °C (on phase) and completely shut off at 20 °C (off phase). Meanwhile Gd2O3:Eu3+ plays an important role as the luminescent tag for tracking the drug loading and release process by the reversible luminescence quenching and recovery phenomenon. These results indicate that the obtained multifunctional composite has the potential to be used as a smart DDS for biomedical applications.

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Section: Discussionmentioning

confidence: 99%

Germ cell tumors in patients infected by the human immunodeficiency virus

Fizazi

Amato

Beuzeboc

et al. 2001

Cancer

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“…There is strong experimental evidence supporting this. These mice show a clear somatotroph hypoplasia due to lack of mitogenic activity of GHRH in these cells (35). Mice carrying the little mutation have a GHRH receptor that cannot bind its ligand (34).…”

Section: Discussionmentioning

confidence: 99%

Growth Hormone-Releasing Hormone Stimulates Mitogen-Activated Protein Kinase*

et al. 2000

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GH-releasing hormone (GHRH) can induce proliferation of somatotroph cells. The pathway involving adenylyl cyclase/cAMP/protein kinase A pathway in its target cells seems to be important for this action, or at least it is deregulated in some somatotroph pituitary adenomas. We studied in this work whether GHRH can also stimulate mitogen-activated protein (MAP) kinase. GHRH can activate MAP kinase both in pituitary cells and in a cell line overexpressing the GHRH receptor. Although both protein kinase A and protein kinase C could activate MAP kinase in the CHO cell line studied, neither protein kinase A nor protein kinase C appears to be required for GHRH activation of MAP kinase in this system. However, sequestration of the betagamma-subunits of the G protein coupled to the receptor inhibits MAP kinase activation mediated by GHRH. This pathway also involves p21ras and a phosphatidylinositol 3-kinase, probably phosphatidylinositol 3-kinase-gamma. Despite the involvement of p21ras, the protein kinase Raf-1 is not hyperphosphorylated in response to GHRH, contrary to what usually occurs when the Ras-Raf-MAP kinase pathway is activated. In summary, this work describes for the first time the activation of MAP kinase by GHRH and outlines a path for this activation that is different from the cAMP-dependent mechanism that has been traditionally described as mediating the mitogenic actions of GHRH.

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“…GHRH is an important factor for somatotroph development and GH synthesis, and the number of somatotrophs and the GH content per somatotroph are reduced in the little mouse (28,31). Similarly, the pituitary glands of our and other patients with the GHRH-R deficiency are small (12) (Baumann, G., H. G. Maheshwari, E. J. Russell; unpublished).…”

Section: Discussionmentioning

confidence: 67%

Selective Lack of Growth Hormone (GH) Response to the GH-Releasing Peptide Hexarelin in Patients with GH-Releasing Hormone Receptor Deficiency¹

Maheshwari¹,

Rahim²,

Shalet³

et al. 1999

The Journal of Clinical Endocrinology & Metabolism

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The mechanism of the synergistic relationship between GH-releasing peptide (GHRP) and GHRH with respect to GH secretion is poorly understood. We report the response to hexarelin, a potent GHRP, in patients affected with a homozygous mutation in the GHRH receptor gene, with consequent GHRH resistance and GH-deficient dwarfism. This newly described syndrome is the human homolog of the little (lit/lit) mouse. Intravenous administration of hexarelin (2 g/kg) to four male adult patients (dwarfs of Sindh) resulted in a complete lack of elevation in plasma GH levels (Ͻ1 ng/mL), an at least 50-to 100-fold deviation from the normal response. In contrast, plasma PRL, ACTH, and cortisol levels rose in a normal manner in response to hexarelin. We conclude that an intact GHRH signaling system is critical for GHRPs to exert their effect on GH release, but that the GHRH system is not necessary for the effect of GHRP on PRL and ACTH secretion. Hexarelin (and probably other GHRPs) are not effective agents for the treatment of patients with GHRH resistance due to GHRH receptor deficiency. (J Clin Endocrinol Metab 84: 956 -959, 1999) T HE GH-RELEASING peptides (GHRP) are a class of small peptides that stimulate GH and, to a lesser degree, PRL and ACTH secretion from the pituitary gland (1-3). They interact with a recently cloned specific receptor that is expressed in the hypothalamus and pituitary (4). Orally active nonpeptide GHRP mimetics that bind to the same receptor and act as GH/PRL/ACTH secretagogues have been developed (3). The GHRPs are believed to represent analogs of a still unknown endogenous ligand for the GHRP receptor. This putative ligand is thought to participate in the regulation of GH secretion, in conjunction with GHRH and somatostatin. GHRPs synergize with GHRH in releasing GH by an unknown, primarily hypothalamic mechanism; coadministration of GHRP with GHRH in vivo results in a large potentiation of the GHRH effect (5, 6). The effect of GHRP on GHRH action at the pituitary level is smaller and additive rather than synergistic (7,8). Despite efforts at elucidating the GHRH-GHRP relationship, the nature of their interaction remains poorly understood, partly because of the difficulty in isolating the effects of GHRH, somatostatin, and GHRP in vivo.To shed further light on the cross-talk between GHRH and GHRP, we studied individuals with a unique new syndrome of genetic GHRH receptor (GHRH-R) deficiency (dwarfism of Sindh) (9, 10) to determine the efficacy of GHRP in elaborating GH, PRL, and ACTH release in the absence of GHRH signaling. Patients affected by this mutation in the GHRH-R are profoundly GH deficient because of GHRH resistance at the pituitary level (9 -12). A practical aim of the study was to determine whether GHRP or its oral analogs may represent a therapeutic modality for the affected patients who live in a rural area of Pakistan where medical services are limited. Hexarelin, the GHRP used in this study, is a potent GHRP whose effects in normal human subjects are well characterized (1...

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Quantitative Aspects of Growth Hormone Cell Maturation in the Normal and Little Mutant Mouse

Cited by 22 publications

References 6 publications

Germ cell tumors in patients infected by the human immunodeficiency virus

Germ cell tumors in patients infected by the human immunodeficiency virus

Growth Hormone-Releasing Hormone Stimulates Mitogen-Activated Protein Kinase*

Selective Lack of Growth Hormone (GH) Response to the GH-Releasing Peptide Hexarelin in Patients with GH-Releasing Hormone Receptor Deficiency¹

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Quantitative Aspects of Growth Hormone Cell Maturation in the Normal and Little Mutant Mouse

Cited by 22 publications

References 6 publications

Germ cell tumors in patients infected by the human immunodeficiency virus

Germ cell tumors in patients infected by the human immunodeficiency virus

Growth Hormone-Releasing Hormone Stimulates Mitogen-Activated Protein Kinase*

Selective Lack of Growth Hormone (GH) Response to the GH-Releasing Peptide Hexarelin in Patients with GH-Releasing Hormone Receptor Deficiency1

Contact Info

Product

Resources

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Selective Lack of Growth Hormone (GH) Response to the GH-Releasing Peptide Hexarelin in Patients with GH-Releasing Hormone Receptor Deficiency¹