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Terry G. Unterman - One of the best experts on this subject based on the ideXlab platform.
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Printed in U.S.A. Copyright © 1998 by The Endocrine Society Hypothalamic/Pituitary-Axis of the Spontaneous Dwarf Rat: Autofeedback Regulation of Growth Hormone (GH) Includes Suppression of GH Releasing-Hormone Receptor Messenger Ribonucleic Acid*
2013Co-Authors: Jun Kamegai, Terry G. Unterman, Lawrence A. Frohman, Rhonda D. KinemanAbstract:In this study, the spontaneous Dwarf Rat (SDR) has been used to examine GHRH production and action in the selective absence of endogenous GH. This Dwarf model is unique in that GH is not produced because of a point mutation in the GH gene. However, other pituitary hormones are not obviously compromised. Examination of the hypothalamic pituitary-axis of SDRs revealed that GHRH messenger RNA (mRNA) levels were increased, whereas somatostatin (SS) and neuropeptide Y (NPY) mRNA levels were decreased, compared with age- and sex-matched normal controls, as determined by Northern blot analysis (n � 5 animals/group; P � 0.05). The elevated levels of GHRH mRNA in the SDR hypothalamus were accompanied by a 56 % increase in pituitary GHRH receptor (GHRH-R) mRNA, as determined by RT-PCR (P � 0.05). To investigate whether the upregulation of GHRH-R mRNA resulted in an increase in GHRH-R function, SDR and control pituitary cell cultures were challenged with GHRH (0.001–10 nM; 15 min), and intracellular cAMP concentRations were measured by RIA. Interestingly, SDR pituitary cells were hyperresponsive to 1 and 10 nM GHRH, which induced a rise in intracellular cAMP concentRations 50 % greater than that observed in control cultures (n � 3 sepaRate experiments; P � 0.05 and P � 0.01
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disruption of growth hormone signaling retards prostate carcinogenesis in the probasin tag Rat
Endocrinology, 2008Co-Authors: Zhuohua Wang, Tomoyuki Shirai, Raúl M. Luque, Rhonda D. Kineman, Vera Ray, Konstantin Christov, Daniel D. Lantvit, Samad Hedayat, Terry G. UntermanAbstract:We asked whether down-regulation of GH signaling could block carcinogenesis in the Probasin/TAg Rat, a model of aggressive prostate cancer. The Spontaneous Dwarf Rat, which lacks GH due to a mutation (dr) in its GH gene, was crossed with the Probasin/TAg Rat, which develops prostate carcinomas at 100% incidence by 15 wk of age. Progeny were heterozygous for the TAg oncogene and homozygous for either the wild-type GH gene (TAg/Gh(+/+)) or the dr mutation (TAg/Gh(dr/dr)). Prostate tumor incidence and burden were significantly reduced, and tumor latency was delayed in TAg/Gh(dr/dr) Rats relative to TAg/Gh(+/+) controls. At 25 wk of age, loss of GH resulted in a 20 and 80% decrease in the area of microinvasive carcinoma in the dorsal and lateral lobes, respectively. By 52 wk of age, invasive prostate adenocarcinomas were observed in all TAg/Gh(+/+) Rats, whereas the majority of TAg/Gh(dr/dr) did not develop invasive tumors. Suppression of carcinogenesis could not be attributed to alteRations in prostate expression of TAg or androgen receptor or changes in serum testosterone levels. As carcinogenesis progressed in TAg/Gh(+/+) Rats, prostate GHR mRNA and protein expression increased significantly, but prostate IGF-I receptor mRNA and protein levels dropped. Furthermore, serum IGF-I and prostate IGF-I levels did not change significantly over the course of carcinogenesis. These findings suggest that GH plays a dominant role in progression from latent to malignant prostate cancer driven by the powerful probasin/TAg fusion gene in Rats and suggest that GH antagonists may be effective at treating human prostate cancer.
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Disruption of Growth Hormone Signaling Retards Prostate Carcinogenesis in the Probasin/TAg Rat
Endocrinology, 2007Co-Authors: Zhuohua Wang, Tomoyuki Shirai, Raúl M. Luque, Rhonda D. Kineman, Vera Ray, Konstantin Christov, Daniel D. Lantvit, Samad Hedayat, Terry G. Unterman, Maarten C. BoslandAbstract:We asked whether down-regulation of GH signaling could block carcinogenesis in the Probasin/TAg Rat, a model of aggressive prostate cancer. The Spontaneous Dwarf Rat, which lacks GH due to a mutation (dr) in its GH gene, was crossed with the Probasin/TAg Rat, which develops prostate carcinomas at 100% incidence by 15 wk of age. Progeny were heterozygous for the TAg oncogene and homozygous for either the wild-type GH gene (TAg/Gh(+/+)) or the dr mutation (TAg/Gh(dr/dr)). Prostate tumor incidence and burden were significantly reduced, and tumor latency was delayed in TAg/Gh(dr/dr) Rats relative to TAg/Gh(+/+) controls. At 25 wk of age, loss of GH resulted in a 20 and 80% decrease in the area of microinvasive carcinoma in the dorsal and lateral lobes, respectively. By 52 wk of age, invasive prostate adenocarcinomas were observed in all TAg/Gh(+/+) Rats, whereas the majority of TAg/Gh(dr/dr) did not develop invasive tumors. Suppression of carcinogenesis could not be attributed to alteRations in prostate expression of TAg or androgen receptor or changes in serum testosterone levels. As carcinogenesis progressed in TAg/Gh(+/+) Rats, prostate GHR mRNA and protein expression increased significantly, but prostate IGF-I receptor mRNA and protein levels dropped. Furthermore, serum IGF-I and prostate IGF-I levels did not change significantly over the course of carcinogenesis. These findings suggest that GH plays a dominant role in progression from latent to malignant prostate cancer driven by the powerful probasin/TAg fusion gene in Rats and suggest that GH antagonists may be effective at treating human prostate cancer.
M J Waters - One of the best experts on this subject based on the ideXlab platform.
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growth hormone gh regulation of submandibular gland structure and function in the gh deficient Rat upregulation of haptocorrin
Journal of Endocrinology, 1997Co-Authors: Peter E Lobie, M J WatersAbstract:Based on localization studies of the GH receptor/binding protein (BP) in the gastrointestinal tract, we have recently demonstRated growth hormone regulation of gastric intrinsic factor. In order to define the role of GH in the submandibular gland (SMG) we have investigated the eVect of GH on SMG structure and function with particular reference to haptocorrin. Bovine GH (65 µg/100 g body weight) was administered twice daily to adult male Dwarf Rats for 6 days (DW+) while control animals received vehicle (DW-). AdministRation of GH produced a significant increase in body weight (P<0·001) and an allometric increase in SMG weight (P=0). There was no change in RNA or protein content per g SMG and GH administRation produced a small decrease in DNA content normalized to SMG weight. Morphometric analysis of the SMG revealed a significant increase in the percentage area of the gland occupied by tubular (GH receptor/BP expressing) structures and a significant increase in the diameter of both the intralobular striated and granular convoluted tubules. The eVect of GH on cellular prolifeRation in the ductular and acinar components was determined by the immunohistochemical detection of nuclear 5*-bromo-2*-deoxyuridine (BrdU) incorpoRated during a 2-h pulse of BrdU. GH treatment induced a 5·5-fold increase in the labelling index of tubular cells whereas the acinar cell labelling index increased only 3·3-fold. Soluble extracts of SMG were prepared for estimation of 57 Co-cyanocobalamin (vitamin B12) binding. GH administRation resulted in an increase in total 57 Cocyanocobalamin (CBL) binding per mg SMG protein. To determine the contribution of haptocorrin (R-protein) the amount of cobinamide dicyanide (CD) displaceable binding was calculated. GH administRation produced a 70% increase in CD displaceable CBL binding per mg SMG indicating GH regulation of haptocorrin. A comparison of total SMG CBL binding and CD displaceable CBL binding between male and female Rats detected no sex diVerence. Therefore sex-specific GH secretory profiles are unlikely to be of importance in the regulation of haptocorrin. In conclusion we have demonstRated that GH stimulates hypertrophy and hyperplasia of components of the SMG in the Dwarf Rat. The observed upregulation of haptocorrin may synergize with the GH-stimulated increase in intrinsic factor to facilitate absorption of CBL during the anabolic state.
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Effect of growth hormone on the distribution of decorin and biglycan during odontogenesis in the Rat incisor
'SAGE Publications', 1995Co-Authors: C.z. Zhang, W. G. Young, Li H, Pm Bartold, M J WatersAbstract:Previous studies have shown that growth hormone can influence the expression of N-acetylgalactosamine-containing molecules in the extracellular matrix of developing Rat incisors. N-acetylgalactosamine is a principal component of proteoglycans containing chondroitin sulfate and dermatan sulfate, as well as of some glycoproteins. Since chondroitin sulfate proteoglycans are identifiable components in enamel, dentin, and cementum, we have tested the hypothesis that growth hormone modulates their expression in developing Rat incisors. The distribution of the chondroitin-sulfate-rich proteoglycans, decorin and biglycan, was investigated. We used the Lewis Dwarf Rat as a model because their circulating growth hormone levels are markedly reduced. Polyclonal antibodies against decorin and biglycan were used to localize these two proteoglycans. Semi-quantitative assessments of the staining patterns and intensities were made for each proteoglycan within compartments of the developing teeth. In normal Lewis Rats, decorin and biglycan differentially expressed throughout the enamel organ, dental papilla, and dental follicle. Decorin displayed a wide distribution throughout all three regions and was closely associated with different cellular components. In contrast, biglycan showed little association with cells and was identified in the predentin and osteoid matrices. The expression of both proteoglycans was dramatically decreased in the, growth-hormone-deficient animals. AdministRation of growth hormone to the Dwarf Rats markedly elevated the expression of both proteoglycans, approximating the distribution and intensity of staining seen in normal animals. These findings confirm that growth hormone status can modulate the expression of decorin and biglycan, and hence matrix deposition, in the Rat tooth
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Growth-Hormone Regulates An N-Acetylgalactosamine Component in Odontogenesis - a Specific Lectin-Binding Study in the Lewis Dwarf Rat
'Wiley', 1994Co-Authors: C.z. Zhang, W. G. Young, Li H, Breipohl W, Doehrn S, M J WatersAbstract:Dental organs of incisors from normal, Dwarf and growth hormone-treated Dwarf Rats were analysed histochemically using a panel of lectins. A distinctive pattern of differential staining was obtained with Helix pomatia agglutinin, a lectin specific for N-acetylgalactosamine. In Bouin's perfused and paraffin-embedded undecalcified tissues from normal Rats, reaction product for N-acetylgalactosamine was Visible in the odontogenic cells and some extracellular matrices. In the growth hormone-deficient Dwarf Rats, the N-acetylgalactosamine reaction was consistently minimal in the odontoblasts, predentin, cementoblasts, cementoid, osteoblasts and osteoid matrices, although the staining of ameloblasts and osteoclasts was similar to normal. AdministRation of growth hormone to Dwarf Rats for six days (66 mu g/100 g Rat b.i.d.) restored the reaction for N-acetylgalactosamine in the affected matrices. Thus, an N-acetylgalactosamine rich matrix component is differentially expressed during odontogenesis. Growth hormone may regulate this component in these matrices, which may be a proteoglycan or a glycoprotein, essential for normal growth of the teeth
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Serum Growth-Hormone Binding-Protein and Hepatic Gh Binding-Sites in the Lewis Dwarf Rat - Effects of Igf-I and Gh
'Elsevier BV', 1994Co-Authors: Barnard R, Wyse B, P. C. Owens, Scott W. Rowlinson, Garciaaragon J, Mulcahy J, Talamantes F, Wr Baumbach, M J WatersAbstract:A radioimmunoassay (RIA) for the Rat growth hormone binding protein (GHBP) was developed using a synthetic peptide (corresponding to the hydrophilic carboxyl-terminal sequence of mouse GHBP) as standard and a monoclonal antibody (MAb 4.3) reactive with this peptide as the primary antibody. The values for GHBP concentRation obtained for normal Rats using this assay compare favourably with those obtained by gel filtRation and ELISA methods. The concentRation of GHBP in normal male Rats at 11 weeks of age (680+/-30 ng/ml, SEM, n=9) was significantly less than the concentRation in normal females (943+/-47 ng/ml, SEM, n=25). In 11-week-old Dwarf male Rats the concentRation of GHBP was 423+/-35 ng/ml (n=8); less than in Dwarf females (542+/-32,
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The Influence of Growth-Hormone On Cell-ProlifeRation in Odontogenic Epithelia by Bromodeoxyuridine Immunocytochemistry and Morphometry in the Lewis Dwarf Rat
'SAGE Publications', 1992Co-Authors: W. G. Young, C.z. Zhang, Li H, Osborne P, M J WatersAbstract:For investigation of how growth hormone affects tooth development, bromodeoxyuridine immunocytochemistry and morphometry were used for the study of cell prolifeRation in odontogenic epithelial cell layers. The number of cells in the S phase, as revealed by this technique, and in mitosis, were counted in Bouin's-perfused and paraffin-embedded undecalcified maxillary incisor enamel organs of normal Rats, in growth-hormone-deficient Dwarf Rats, and in Dwarf Rats treated with growth hormone (66 mug/100 g body wt) twice daily for six days. Significantly fewer labeled nuclei, unlabeled nuclei, and total nuclei of various odontogenic epithelia were found in Dwarf Rats, but in Dwarf Rats treated with growth hormone, numbers of labeled nuclei equivalent to normal were found in the internal enamel epithelium, stRatum intermedium, and Hertwig root sheath. Moreover, the mitotic index for pre-ameloblasts was 1.64 in normal Rats, 0.92 for Dwarf Rats, and 1.66 for growth-hormone-treated Dwarf Rats (SD, 0. 10). Other parameters-such as the labeling index and the Ratio of positive to negative nuclei-were similarly related to GH status. Thus, growth hormone may play a role in the prolifeRation of the odontogenic epithelia in the Rat
Zhuohua Wang - One of the best experts on this subject based on the ideXlab platform.
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disruption of growth hormone signaling retards prostate carcinogenesis in the probasin tag Rat
Endocrinology, 2008Co-Authors: Zhuohua Wang, Tomoyuki Shirai, Raúl M. Luque, Rhonda D. Kineman, Vera Ray, Konstantin Christov, Daniel D. Lantvit, Samad Hedayat, Terry G. UntermanAbstract:We asked whether down-regulation of GH signaling could block carcinogenesis in the Probasin/TAg Rat, a model of aggressive prostate cancer. The Spontaneous Dwarf Rat, which lacks GH due to a mutation (dr) in its GH gene, was crossed with the Probasin/TAg Rat, which develops prostate carcinomas at 100% incidence by 15 wk of age. Progeny were heterozygous for the TAg oncogene and homozygous for either the wild-type GH gene (TAg/Gh(+/+)) or the dr mutation (TAg/Gh(dr/dr)). Prostate tumor incidence and burden were significantly reduced, and tumor latency was delayed in TAg/Gh(dr/dr) Rats relative to TAg/Gh(+/+) controls. At 25 wk of age, loss of GH resulted in a 20 and 80% decrease in the area of microinvasive carcinoma in the dorsal and lateral lobes, respectively. By 52 wk of age, invasive prostate adenocarcinomas were observed in all TAg/Gh(+/+) Rats, whereas the majority of TAg/Gh(dr/dr) did not develop invasive tumors. Suppression of carcinogenesis could not be attributed to alteRations in prostate expression of TAg or androgen receptor or changes in serum testosterone levels. As carcinogenesis progressed in TAg/Gh(+/+) Rats, prostate GHR mRNA and protein expression increased significantly, but prostate IGF-I receptor mRNA and protein levels dropped. Furthermore, serum IGF-I and prostate IGF-I levels did not change significantly over the course of carcinogenesis. These findings suggest that GH plays a dominant role in progression from latent to malignant prostate cancer driven by the powerful probasin/TAg fusion gene in Rats and suggest that GH antagonists may be effective at treating human prostate cancer.
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Disruption of Growth Hormone Signaling Retards Prostate Carcinogenesis in the Probasin/TAg Rat
Endocrinology, 2007Co-Authors: Zhuohua Wang, Tomoyuki Shirai, Raúl M. Luque, Rhonda D. Kineman, Vera Ray, Konstantin Christov, Daniel D. Lantvit, Samad Hedayat, Terry G. Unterman, Maarten C. BoslandAbstract:We asked whether down-regulation of GH signaling could block carcinogenesis in the Probasin/TAg Rat, a model of aggressive prostate cancer. The Spontaneous Dwarf Rat, which lacks GH due to a mutation (dr) in its GH gene, was crossed with the Probasin/TAg Rat, which develops prostate carcinomas at 100% incidence by 15 wk of age. Progeny were heterozygous for the TAg oncogene and homozygous for either the wild-type GH gene (TAg/Gh(+/+)) or the dr mutation (TAg/Gh(dr/dr)). Prostate tumor incidence and burden were significantly reduced, and tumor latency was delayed in TAg/Gh(dr/dr) Rats relative to TAg/Gh(+/+) controls. At 25 wk of age, loss of GH resulted in a 20 and 80% decrease in the area of microinvasive carcinoma in the dorsal and lateral lobes, respectively. By 52 wk of age, invasive prostate adenocarcinomas were observed in all TAg/Gh(+/+) Rats, whereas the majority of TAg/Gh(dr/dr) did not develop invasive tumors. Suppression of carcinogenesis could not be attributed to alteRations in prostate expression of TAg or androgen receptor or changes in serum testosterone levels. As carcinogenesis progressed in TAg/Gh(+/+) Rats, prostate GHR mRNA and protein expression increased significantly, but prostate IGF-I receptor mRNA and protein levels dropped. Furthermore, serum IGF-I and prostate IGF-I levels did not change significantly over the course of carcinogenesis. These findings suggest that GH plays a dominant role in progression from latent to malignant prostate cancer driven by the powerful probasin/TAg fusion gene in Rats and suggest that GH antagonists may be effective at treating human prostate cancer.
Rhonda D. Kineman - One of the best experts on this subject based on the ideXlab platform.
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Printed in U.S.A. Copyright © 1998 by The Endocrine Society Hypothalamic/Pituitary-Axis of the Spontaneous Dwarf Rat: Autofeedback Regulation of Growth Hormone (GH) Includes Suppression of GH Releasing-Hormone Receptor Messenger Ribonucleic Acid*
2013Co-Authors: Jun Kamegai, Terry G. Unterman, Lawrence A. Frohman, Rhonda D. KinemanAbstract:In this study, the spontaneous Dwarf Rat (SDR) has been used to examine GHRH production and action in the selective absence of endogenous GH. This Dwarf model is unique in that GH is not produced because of a point mutation in the GH gene. However, other pituitary hormones are not obviously compromised. Examination of the hypothalamic pituitary-axis of SDRs revealed that GHRH messenger RNA (mRNA) levels were increased, whereas somatostatin (SS) and neuropeptide Y (NPY) mRNA levels were decreased, compared with age- and sex-matched normal controls, as determined by Northern blot analysis (n � 5 animals/group; P � 0.05). The elevated levels of GHRH mRNA in the SDR hypothalamus were accompanied by a 56 % increase in pituitary GHRH receptor (GHRH-R) mRNA, as determined by RT-PCR (P � 0.05). To investigate whether the upregulation of GHRH-R mRNA resulted in an increase in GHRH-R function, SDR and control pituitary cell cultures were challenged with GHRH (0.001–10 nM; 15 min), and intracellular cAMP concentRations were measured by RIA. Interestingly, SDR pituitary cells were hyperresponsive to 1 and 10 nM GHRH, which induced a rise in intracellular cAMP concentRations 50 % greater than that observed in control cultures (n � 3 sepaRate experiments; P � 0.05 and P � 0.01
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disruption of growth hormone signaling retards prostate carcinogenesis in the probasin tag Rat
Endocrinology, 2008Co-Authors: Zhuohua Wang, Tomoyuki Shirai, Raúl M. Luque, Rhonda D. Kineman, Vera Ray, Konstantin Christov, Daniel D. Lantvit, Samad Hedayat, Terry G. UntermanAbstract:We asked whether down-regulation of GH signaling could block carcinogenesis in the Probasin/TAg Rat, a model of aggressive prostate cancer. The Spontaneous Dwarf Rat, which lacks GH due to a mutation (dr) in its GH gene, was crossed with the Probasin/TAg Rat, which develops prostate carcinomas at 100% incidence by 15 wk of age. Progeny were heterozygous for the TAg oncogene and homozygous for either the wild-type GH gene (TAg/Gh(+/+)) or the dr mutation (TAg/Gh(dr/dr)). Prostate tumor incidence and burden were significantly reduced, and tumor latency was delayed in TAg/Gh(dr/dr) Rats relative to TAg/Gh(+/+) controls. At 25 wk of age, loss of GH resulted in a 20 and 80% decrease in the area of microinvasive carcinoma in the dorsal and lateral lobes, respectively. By 52 wk of age, invasive prostate adenocarcinomas were observed in all TAg/Gh(+/+) Rats, whereas the majority of TAg/Gh(dr/dr) did not develop invasive tumors. Suppression of carcinogenesis could not be attributed to alteRations in prostate expression of TAg or androgen receptor or changes in serum testosterone levels. As carcinogenesis progressed in TAg/Gh(+/+) Rats, prostate GHR mRNA and protein expression increased significantly, but prostate IGF-I receptor mRNA and protein levels dropped. Furthermore, serum IGF-I and prostate IGF-I levels did not change significantly over the course of carcinogenesis. These findings suggest that GH plays a dominant role in progression from latent to malignant prostate cancer driven by the powerful probasin/TAg fusion gene in Rats and suggest that GH antagonists may be effective at treating human prostate cancer.
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Disruption of Growth Hormone Signaling Retards Prostate Carcinogenesis in the Probasin/TAg Rat
Endocrinology, 2007Co-Authors: Zhuohua Wang, Tomoyuki Shirai, Raúl M. Luque, Rhonda D. Kineman, Vera Ray, Konstantin Christov, Daniel D. Lantvit, Samad Hedayat, Terry G. Unterman, Maarten C. BoslandAbstract:We asked whether down-regulation of GH signaling could block carcinogenesis in the Probasin/TAg Rat, a model of aggressive prostate cancer. The Spontaneous Dwarf Rat, which lacks GH due to a mutation (dr) in its GH gene, was crossed with the Probasin/TAg Rat, which develops prostate carcinomas at 100% incidence by 15 wk of age. Progeny were heterozygous for the TAg oncogene and homozygous for either the wild-type GH gene (TAg/Gh(+/+)) or the dr mutation (TAg/Gh(dr/dr)). Prostate tumor incidence and burden were significantly reduced, and tumor latency was delayed in TAg/Gh(dr/dr) Rats relative to TAg/Gh(+/+) controls. At 25 wk of age, loss of GH resulted in a 20 and 80% decrease in the area of microinvasive carcinoma in the dorsal and lateral lobes, respectively. By 52 wk of age, invasive prostate adenocarcinomas were observed in all TAg/Gh(+/+) Rats, whereas the majority of TAg/Gh(dr/dr) did not develop invasive tumors. Suppression of carcinogenesis could not be attributed to alteRations in prostate expression of TAg or androgen receptor or changes in serum testosterone levels. As carcinogenesis progressed in TAg/Gh(+/+) Rats, prostate GHR mRNA and protein expression increased significantly, but prostate IGF-I receptor mRNA and protein levels dropped. Furthermore, serum IGF-I and prostate IGF-I levels did not change significantly over the course of carcinogenesis. These findings suggest that GH plays a dominant role in progression from latent to malignant prostate cancer driven by the powerful probasin/TAg fusion gene in Rats and suggest that GH antagonists may be effective at treating human prostate cancer.
Maarten C. Bosland - One of the best experts on this subject based on the ideXlab platform.
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Disruption of Growth Hormone Signaling Retards Prostate Carcinogenesis in the Probasin/TAg Rat
Endocrinology, 2007Co-Authors: Zhuohua Wang, Tomoyuki Shirai, Raúl M. Luque, Rhonda D. Kineman, Vera Ray, Konstantin Christov, Daniel D. Lantvit, Samad Hedayat, Terry G. Unterman, Maarten C. BoslandAbstract:We asked whether down-regulation of GH signaling could block carcinogenesis in the Probasin/TAg Rat, a model of aggressive prostate cancer. The Spontaneous Dwarf Rat, which lacks GH due to a mutation (dr) in its GH gene, was crossed with the Probasin/TAg Rat, which develops prostate carcinomas at 100% incidence by 15 wk of age. Progeny were heterozygous for the TAg oncogene and homozygous for either the wild-type GH gene (TAg/Gh(+/+)) or the dr mutation (TAg/Gh(dr/dr)). Prostate tumor incidence and burden were significantly reduced, and tumor latency was delayed in TAg/Gh(dr/dr) Rats relative to TAg/Gh(+/+) controls. At 25 wk of age, loss of GH resulted in a 20 and 80% decrease in the area of microinvasive carcinoma in the dorsal and lateral lobes, respectively. By 52 wk of age, invasive prostate adenocarcinomas were observed in all TAg/Gh(+/+) Rats, whereas the majority of TAg/Gh(dr/dr) did not develop invasive tumors. Suppression of carcinogenesis could not be attributed to alteRations in prostate expression of TAg or androgen receptor or changes in serum testosterone levels. As carcinogenesis progressed in TAg/Gh(+/+) Rats, prostate GHR mRNA and protein expression increased significantly, but prostate IGF-I receptor mRNA and protein levels dropped. Furthermore, serum IGF-I and prostate IGF-I levels did not change significantly over the course of carcinogenesis. These findings suggest that GH plays a dominant role in progression from latent to malignant prostate cancer driven by the powerful probasin/TAg fusion gene in Rats and suggest that GH antagonists may be effective at treating human prostate cancer.
