GH gene expression in the submaxillary gland in normal and Ames dwarf mice

High local GH-releasing hormone (GHRH) levels are capable of inducing transdifferentiation in salivary cells to synthesize GH. However, the factors implicated in this process remain unknown. To study this subject, normal and Ames dwarf mice were implanted in the submaxillary gland with a slow release pellet releasing 21 microgram GHRH (1-29)-NH(2)/day for 2 months. Control animals received placebo pellets at the same site. After 60 days, heart blood was collected and submaxillary glands were removed. Circulating levels of GH and IGF-I were significantly decreased (P<0.05) in dwarf mice in comparison with controls, and GHRH treatment did not modify either of these two parameters. Controls carrying GHRH pellets showed a significantly higher GH content (P<0.05) in the submaxillary gland than the placebo-treated normal mice. There were no differences between the IGF-I concentrations of placebo- and GHRH-treated salivary tissue from normal mice. Analysis of GH mRNA by RT-PCR followed by Southern blot revealed that GH transcripts were present in the salivary gland samples carrying the placebo pellets in both normal and dwarf mice. The expression of GH was significantly (P<0.05) increased by the GHRH pellets in salivary tissue from normal mice, but not in submaxillary glands from dwarf mice. Pit-1 mRNA was not detected in the GHRH-treated glands of normal and dwarf mice by RT-PCR or by Southern blot. Using these highly sensitive methods, we have been able to detect the transcription of both GH and Pit-1 in pituitaries from Pit-1-deficient Ames dwarf mice. The present experiment demonstrates that salivary tissue synthesizes GH when it is exposed to the influence of GHRH. Both basal and GHRH-induced salivary GH expression appear to be independent of Pit-1.

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Increased Neurogenesis in Dentate Gyrus of Long-Lived Ames Dwarf Mice

Endocrinology ◽

10.1210/en.2004-1115 ◽

2005 ◽

Vol 146 (3) ◽

pp. 1138-1144 ◽

Cited By ~ 72

Author(s):

Liou Y. Sun ◽

M. Steven Evans ◽

Jenny Hsieh ◽

Jacob Panici ◽

Andrzej Bartke

Keyword(s):

Cognitive Function ◽

Dentate Gyrus ◽

Adult Life ◽

Hippocampal Neurogenesis ◽

Trophic Factors ◽

Nuclear Antigen ◽

Ames Dwarf Mice ◽

Igf I ◽

Ames Dwarf ◽

Dwarf Mice

Neurogenesis occurs throughout adult life in the dentate gyrus of mammalian hippocampus and has been suggested to play an important role in cognitive function. Multiple trophic factors including IGF-I have been demonstrated to regulate hippocampal neurogenesis. Ames dwarf mice live considerably longer than normal animals and maintain physiological function at youthful levels, including cognitive function, despite a deficiency of circulating GH and IGF-I. Here we show an increase in numbers of newly generated cells [bromodeoxyuridine (BrdU) positive] and newborn neurons (neuronal nuclear antigen and BrdU positive) in the dentate gyrus of adult dwarf mice compared with normal mice using BrdU labeling. Despite the profound suppression of hippocampal GH expression, hippocampal IGF-I protein levels are up-regulated and the corresponding mRNAs are as high in Ames dwarf as in normal mice. Our results suggest that local/hippocampal IGF-I expression may have induced the increase in hippocampal neurogenesis, and increased neurogenesis might contribute to the maintenance of youthful levels of cognitive function during aging in these long-lived animals.

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Salivary gland is capable of GH synthesis under GHRH stimulation

Journal of Endocrinology ◽

10.1677/joe.0.1600217 ◽

1999 ◽

Vol 160 (2) ◽

pp. 217-222 ◽

Cited By ~ 12

Author(s):

JA Tresguerres ◽

C Ariznavarreta ◽

B Granados ◽

JA Costoya ◽

A Perez-Romero ◽

...

Keyword(s):

Salivary Gland ◽

In Situ Hybridization ◽

Submaxillary Gland ◽

Treated Group ◽

Female Rats ◽

Submaxillary Glands ◽

Igf I ◽

Heart Blood ◽

Plasma Gh

Twelve female rats weighing approximately 150 g received in the submaxillary gland a pellet capable of releasing 3.5 microg GHRH/h for 60 days. Another eight sex- and weight-matched animals received placebo pellets in the same place. After two months the animals were killed, heart blood was collected and pituitary and submaxillary glands were carefully dissected. Pituitary GH content in both placebo- and GHRH-treated animals showed similar values, but plasma GH and IGF-I levels were significantly lower in the animals carrying GHRH pellets (P<0.03); these animals also had a significantly higher GH content in the submaxillary gland (19.2+/-8 ng/mg protein) compared with the placebo-treated group (1.1+/-0.3 ng/mg protein). GH mRNA was present only in the submaxillary gland of GHRH-treated rats as determined by PCR-Southern blot and by in situ hybridization methods. It is concluded that high local GHRH levels are capable of inducing transdifferentiation in submaxillary gland cells to synthesize GH.

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Endothelial function and vascular oxidative stress in long-lived GH/IGF-deficient Ames dwarf mice

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.412.2008 ◽

2008 ◽

Vol 295 (5) ◽

pp. H1882-H1894 ◽

Cited By ~ 111

Author(s):

Anna Csiszar ◽

Nazar Labinskyy ◽

Viviana Perez ◽

Fabio A. Recchia ◽

Andrej Podlutsky ◽

...

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Ros Generation ◽

No Production ◽

Wild Type ◽

Ames Dwarf Mice ◽

Igf I ◽

Ames Dwarf ◽

Dwarf Mice ◽

Vascular Oxidative Stress

Hypopituitary Ames dwarf mice have low circulating growth hormone (GH)/IGF-I levels, and they have extended longevity and exhibit many symptoms of delayed aging. To elucidate the vascular consequences of Ames dwarfism we compared endothelial O2•− and H2O2 production, mitochondrial reactive oxygen species (ROS) generation, expression of antioxidant enzymes, and nitric oxide (NO) production in aortas of Ames dwarf and wild-type control mice. In Ames dwarf aortas endothelial O2•− and H2O2 production and ROS generation by mitochondria were enhanced compared with those in vessels of wild-type mice. In Ames dwarf aortas there was a less abundant expression of Mn-SOD, Cu,Zn-SOD, glutathione peroxidase (GPx)-1, and endothelial nitric oxide synthase (eNOS). NO production and acetylcholine-induced relaxation were also decreased in aortas of Ames dwarf mice. In cultured wild-type mouse aortas and in human coronary arterial endothelial cells treatment with GH and IGF significantly reduced cellular O2•− and H2O2 production and ROS generation by mitochondria and upregulated expression of Mn-SOD, Cu,Zn-SOD, GPx-1, and eNOS. Thus GH and IGF-I promote antioxidant phenotypic changes in the endothelial cells, whereas Ames dwarfism leads to vascular oxidative stress.

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