The Effects of 20-kDa Human Placental GH in Male and Female GH-deficient Mice: An Improved Human GH?

A rare 20K isoform of GH-V (here abbreviated as GHv) was discovered in 1998. To date, only 1 research article has characterized this isoform in vivo, observing that GHv treatment in male high-fat fed rats had several GH-like activities, but unlike GH lacked diabetogenic and lactogenic activities and failed to increase IGF-1 or body length. Therefore, the current study was conducted to further characterize the in vivo activities of GHv in a separate species and in a GH-deficient model (GH-/- mice) and with both sexes represented. GHv-treated GH-/- mice had significant increases to serum IGF-1, femur length, body length, body weight, and lean body mass and reduced body fat mass similar to mice receiving GH treatment. GH treatment increased circulating insulin levels and impaired insulin sensitivity; in contrast, both measures were unchanged in GHv-treated mice. Since GHv lacks prolactin receptor (PRLR) binding activity, we tested the ability of GH and GHv to stimulate the proliferation of human cancer cell lines and found that GHv has a decreased proliferative response in cancers with high PRLR. Our findings demonstrate that GHv can stimulate insulin-like growth factor-1 and subsequent longitudinal body growth in GH-deficient mice similar to GH, but unlike GH, GHv promoted growth without inhibiting insulin action and without promoting the growth of PRLR-positive cancers in vitro. Thus, GHv may represent improvements to current GH therapies especially for individuals at risk for metabolic syndrome or PRLR-positive cancers.

Inhibition of B16 melanoma growth in vivo by retroviral vector-mediated human ribonuclease inhibitor.

Human ribonuclease inhibitor (hRI) can inhibit angiogenesis by reversibly binding angiogenin, a member of the RNaseA superfamily, and by suppressing the expression of basic fibroblast growth factor (bFGF). Angiogenesis is necessary for the growth and metastasis of tumors. To study the links between hRI, angiogenesis, and melanoma growth, the hRI gene was intravenously administered to mice in a recombinant retroviral vector, and expression of the hRI gene was induced to block melanoma angiogenesis. Expression, distribution, and contribution of the target gene in mice were assayed. The results showed that the tumors of mice in the hRI treatment group grew slower with less vascularity than those of mice in control groups. The introduced hRI gene inhibited tumor growth without causing significant side effects in the animals. More hRI expression in vimentin-positive cells of the tumor than in melanoma cells suggested that mesenchymal cells in the fibrous envelope of the tumor play important roles in this gene therapy.

Antitumor effects of human ribonuclease inhibitor gene transfected on B16 melanoma cells.

Human ribonuclease inhibitor (RI) is a cytoplasmic acidic protein. The experiment demonstrated that it might effectively inhibit tumor-induced angiogenesis and inhibit tumor growth. Ribonuclease inhibitor is constructed almost entirely of leucine-rich repeats, which might be involved in unknown biological effects besides inhibiting RNase A and angiogenin activities. The exact molecular mechanism of antitumor on ribonuclease inhibitor remains unclear so far. In order to further understand the function of ribonuclease inhibitor and investigate the relationship with tumor growth, our study established a transfection of human ribonuclease inhibitor cDNA into the murine B16 cells by the retroviral packaging cell line PA317. The cell line transfected with a stably high expression of ribonuclease inhibitor was identified. We found that the transfected ribonuclease inhibitor could obviously inhibit cell proliferation, regulate cell cycle and induce cell apoptosis in vitro. Mice that were injected with the B16 cells transfected RI cDNA showed a significant inhibition of the tumor growth with lighter tumor weight, lower density of microvessels, longer latent periods, and survival time than those in the other two control groups. In conclusion, the results reveal the novel mechanism that antitumor effect of ribonuclease inhibitor is also associated with inducing apoptosis, regulating cell cycle and inhibiting proliferation besides antiangiogenesis. These results suggest that ribonuclease inhibitor might be a candidate of tumor suppressor gene in some tissues. RI could become a target gene for gene therapy. Our study may be of biological and clinical importance.

Influência de hormonios placentários no parto prematuro / Placentary hormonal influences in premature delivery

Esta revisäo tem por finalidade verificar a correlaçäo existente entre a influência hormonal placentária e a parte prematura. Mesmo sendo discutivel o papel dos hormonios placentários, a queda da progesterona e tida como importante fator desencadeante das contraçöes uterinas. Em vista disto, embora sejam necessários estudos duplo-cegos controlados, recomendamos o uso da progesterona via vaginal em determinadas pacientes com risco elevado para o parto prematuro

[How to stimulate the placental function (author's transl)]. / Cómo estimular la función placentaria.

Imminent abortion, habitual abortion and threatened premature labor, all constitute difficult clinical problems. Those cases require on every occasion a diagnosis as acurate as possible, and unfortunately our present methods of biochemical determinations only represent a means to evaluate placental function. On those cases where a faulty placental function is detected thru the tests presently available, the authors recommend the utilization of a placentotropic substance, Gestanon, that is capable to stimulate and normalize the placental function, a is demostrated by the statistical results published in the international medical bibliography.