Includes bibliographical references (leaves 188-217) Insulin-like growth factor-I circulates at high concentrations in blood, mainly complexed with IGF-binding proteins. The main objective of the thesis is to determine the general role played by plasma IGF-binding proteins in the regulation of IGF transfer from blood to tissues.

Thesis (Ph. D.)--University of Washington, 2006. / Vita. Includes bibliographical references (leaves 44-53).

Thesis (Ph. D.)--University of Washington, 2001. / Vita. Includes bibliographical references (leaves 96-116).

Thesis (Ph. D.)--University of Washington, 2003. / Vita. Includes bibliographical references (leaves 79-87).

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 6 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 5 uppsatser.

Techn. University, Diss., 2005--München.

Dentre os diversos fatores que provocam diminuição no desempenho reprodutivo, a degeneração testicular térmica é o motivo mais freqüente de baixa fertilidade em Bos taurus no Brasil. Baseados nos efeitos sobre a secreção de hormônios hipofisários e gonadais, o GH vem sendo estudado para o tratamento da infertilidade masculina. Um delineamento experimental tipo blocos ao acaso utilizou dezesseis touros adultos submetidos a 4 tratamentos em esquema fatorial 2x2 (0 e 96 horas de insulação testicular, 0 e 1,2 mg bST/kg PV), com o objetivo de testar os efeitos da bST no tratamento de touros submetidos a insulação testicular. Motilidade, alterações de acrossoma, defeitos de cauda e cabeça, gota protoplasmática proximal e defeitos espermáticos totais aumentaram em conseqüência da insulação testicular. As concentrações seminais de Testosterona foram temporariamente diminuídas em resposta a insulação testicular. A ocorrência de gota protoplasmática distal, anomalias de peça intermediária e concentrações seminais de IGF1 não foram afetadas pela insulação testicular. A somatotropina recombinante bovina não afetou as características espermáticas ou concentrações seminais de Testosterona e IGF1. / Testicular heat degeneration is the most common cause of poor fertility of Bos taurus bulls in the tropics. The Growth Hormone has been studied in man infertility treatment with some progress. A randomly blocks experimental design used 16 mature bulls allotted in 4 treatments in a 2x2 factorial arrangement (0 e 96 hours of scrotal insulation, 0 e 1,2 mg bST/kg BW) was performed to asses the effects ob bulls submitted to scrotal insulation. Motility, abnormal acrosome, tail and head defects, proximal droplet, and abnormal sperm increased, and seminal plasma Testosterone was temporally increased in response to scrotal insulation. Distal droplet, midpiece and seminal plasma IGF1 were not affected by bST. The bST did not affect sperm characteristics or seminal Testosterone and IGF1.

Breast cancer is a leading cause of cancer death of women in the U.S. today. Members of the family of insulin-like growth factors (IGFs) are proposed to play a major role in the development and subsequent uncontrolled proliferation of breast cancer cells. Insulin-like growth factor-I (IGF-I) is known to be a potent mitogen for mammary epithelial cells. IGF-I acts by binding to cell surface receptors, thereby stimulating a cascade of events leading to cell division. In the interest of interrupting the effect of IGF-I on cancerous mammary epithelial cells, an understanding of how IGF-I behaves in the presence of other extracellular components is needed. This study examines the IGF-I response of SV40-IGF-I, an immortalized bovine mammary epithelial cell line which secretes IGF-I constitutively. The microphysiometer allows real-time sampling of cellular activity by measuring the excretion of protons from a sample of cells stimulated by IGF-I binding. The contributions of other factors in enhancing or suppressing stimulation can be compared by examining the pH response of cells exposed to IGF-I in the presence of these factors. We present data showing the stimulatory effect of IGF-I in a dose dependent manner on the SV40-IGF-I cell line. In addition, we compare IGF-I stimulation with stimulation by long R3IGF-I, a substituted analogue of IGF-I having a reduced binding affinity for the IGF binding proteins. We examine the effect of insulin-like binding protein-3 (IGFBP-3) both in the presence and absence of IGF-I, finding no IGF-I independent effect in the rapid binding experiment and no effect on stimulation of IGFBP-3 pre-incubated cells by subsequent IGF-I challenge. This is of particular interest due to recent work demonstrating an IGF-independent IGFBP-3 response in a number of cell lines. Binding studies to correlate with the rapid binding stimulation show binding of the IGFBP-3 molecule with high affinity to a small number of surface receptors on the SV40-IGF-I cell. Analysis of the extracellular environment and the components contributing to the binding of IGF-I to the cell membrane receptor will provide information for the development of interventions to slow or interrupt the process of IGF-I binding and therefore cancer growth. Optimization of the Cytosensor(r) Microphysiometer System for the (transfected) SV40-IGF-I and the (parental) MAC-T cell lines was achieved to continue comparison studies of autocrine and paracrine stimulation of bovine mammary epithelial cells by IGF-I. This work was supported by the Whitaker Foundation Biomedical Engineering Grant. / Master of Science

Diss. (sammanfattning) Linköping : Univ., 2004. / Härtill 6 uppsatser.