Growth and Bone Changes in Rats Injected With Alkaline Anterior Pituitary Extracts.

Handelsman, Milton B.; Gordon, Ernest F.

doi:10.3181/00379727-27-4788

Cited by 3 publications

(1 citation statement)

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“…The animal model for GH deficiency is a hypophysectomized rat. It has been known for some time that hypopbysectomy causes a decrease in epiphysial cartilage width in the immature rat (Dott and Fraser, 1923;Ray et al, 1941), and that administration of the exttacts from the anterior pituitary lobe partially reverses this effect (Dott, 1923;Handelsman and Gordon, 1930;Smith, 1930). Freud and coworkers further found that the pituitary GH increased the thickness of the tibia growth plate, which primarily stimulates the proliferation of chondrocytes (Freud et al, 1939).…”

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confidence: 93%

Long-Term Expression of the Biologically Active Growth Hormone in Genetically Modified Fibroblasts after Implantation into a Hypophysectomized Rat

Chen¹,

Chang²,

Chen³

et al. 1995

Human Gene Therapy

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We employed the hypophysectomized rats as an animal model to explore the feasibility of using genetically engineered fibroblast cells for growth hormone gene therapy. An internal ribosome entry site (IRES)-directed bicistronic retroviral vector, PSN, which contained a porcine growth hormone (pGH) cDNA at the first cistron and a Neo(r) gene at the second cistron was used to infect primary rat embryo fibroblast (REF) cells. The infected cells (5 x 10(6) cells/rat) were injected directly into the peritoneum of syngeneic hypophysectomized rats. We demonstrate that the implanted PSN-infected REF cells could secrete biologically active pGH in vivo, leading to significant growth of the tibia at day 15 and day 57 post-implantation. We also treated the PSN-infected REF cells with collagen to form a tissue-like structure. The skin-like discs were grafted underneath the skin on the back of rats and cells were retrieved at different times. Using two criteria, semiquantitative reverse transcription-polymerase chain reaction on the pGH RNA extracted from the explants and G418 resistance conferred from the explanted cells, we demonstrate that pGH was expressed in the implanted fibroblasts up to 70 days. Despite the fact that the total pGH RNA level was reduced in the explants of long-time post-implantation, which was probably due to the reduction of transduced cells retained in the explants, the specific efficiencies of pGH RNA expression from these explants were maintained as high as the primary PSN-infected REF prior implantation. These results suggest that fibroblast cells are capable of expressing the foreign genes persistently in vivo.

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confidence: 93%