Testes-specific transgene expression in insulin-like growth factor-I transgenic mice.

Insulin-like growth factor-I (IGF-I) is a low molecular weight peptide that mediates the cell proliferating actions of growth hormone. Evidence exists indicating that IGF-I is produced by various cell types and this growth factor has been implicated in a variety of reproductive processes. To investigate the effect of IGF-I over-expression on reproductive systems, we generated three independent lines of transgenic mice harbouring a human IGF-I cDNA (hIGF-I) under the control of a Cytomegalovirus immediate early (CMV) promoter. The CMV promoter was used in an attempt to direct expression of IGF-I into a variety of tissues both reproductive and non-reproductive. Yet expression of the foreign hIGF-I gene, determined by Northern blot, was found to occur only in the testicular tissues of the male mice, apparently due to methylation of the transgene in all the tissues tested except the testes, which demonstrate transgene hypomethylation. Evaluation of the transgene expression during testicular development revealed that expression begins between 10 and 15 days of development, coinciding with the appearance of the zygotene and pachytene primary spermatocytes during early spermatogenesis, therefore indicating germ line expression of the transgene. Extensive study of the CMV-hIGF-I transgenic lines of mice has revealed that the effects of the transgene expression do not extend beyond the testicular tissues. No significant differences (P > 0.05) in the IGF-I serum levels, growth rates, or testicular histology have been observed between transgenic and non-transgenic male siblings. The ability of transgenic males to produce offspring also appears unaffected. Evaluation of the IGF binding protein (IGFBP) levels in the testicular tissues of CMV-hIGF-I transgenic mice by Western ligand blot revealed an increase in the concentration of testicular proteins with molecular weights corresponding to IGFBP-2 and IGFBP-3. These results suggest that the testicular over-expression of IGF-I induces increased IGFBP localization in this tissue. Inhibition of IGF activity by the IGFBPs would explain the lack of a dramatic physiological effect in the CMV-hIGF-I transgenic mice, despite the presence of elevated testicular IGF-I. The observation that testis specific IGF-I overexpression induces localization of IGFBPs in this tissue confirms the existence of a well regulated testicular IGF system and supports the convention that this growth factor plays an important role in testicular function.

Dyck MK ，Ouellet M ，Gagn M ，Petitclerc D ，Sirard MA ，Pothier F ... -  《MOLECULAR REPRODUCTION AND DEVELOPMENT》

Heparin-binding EGF-like growth factor (HB-EGF) overexpression in transgenic mice downregulates insulin-like growth factor binding protein (IGFBP)-3 and -4 mRNA.

Provenzano AP ，Besner GE ，James PF ，Harding PA ... -  《GROWTH FACTORS》

Osteoblast-specific expression of insulin-like growth factor-1 in bone of transgenic mice induces insulin-like growth factor binding protein-5.

Rutter MM ，Markoff E ，Clayton L ，Akeno N ，Zhao G ，Clemens TL ，Chernausek SD ... -  《-》

Developmental changes in the mRNA levels of IGF-I and its related genes in the reproductive organs of Japanese quail (Coturnix coturnix japonica).

Summary Insulin-like growth factor-I (IGF-I) is involved in the regulation of growth and differentiation of a variety of vertebrate tissues. The biological actions of IGF-I are mediated mainly by the IGF-I receptor (IGF-IR) and partly by the insulin receptor (IR) and modulated by IGF binding proteins (IGFBP). We conducted studies designed to clarify the possible roles of IGF system in the development of the avian reproductive organs. We cloned cDNAs of IGF-I, IGF-IR, IR and IGFBP-2 of Japanese quail and simultaneously measured the expression of these genes in the quail liver, testis and oviduct at different ages using a lysate RNase protection assay. Hepatic IGF-I mRNA levels increased rapidly and remained elevated during the rapid-growing period, which coincided with the period of rapid increase in testicular weight. IGF-I mRNA was detected at each stage of developing testis examined. Its level was high at the early stage and decreased with age. IGFBP-2 mRNA in testis exhibited a similar expression pattern to that of IGF-I, whereas a divergence in IGF-I and IGF-IR gene expression was observed. Both IGF-IR and IR mRNAs increased when the testis grew rapidly and decreased when sexual maturation was almost completed. These results suggest that IGF-I may serve as an autocrine/paracrine regulator as well as an endocrine regulator in the testicular development and function of Japanese quail. In the oviduct, IGF-I, IGF-IR, IR and IGFBP-2 mRNAs were also developmentally regulated. A rapid growth of the oviduct was accompanied by a significant increase in the level of IGF-I mRNA. The expression of genes encoding IGF-IR, IR and IGFBP-2 in the oviduct exhibited a similar developmental change to that of IGF-I. These results suggest that IGF-I mainly works in an autocrine and/or paracrine manner in the oviduct during the development of this organ. The findings of the present study provide further evidence of an important role for IGF system in the development and function of the avian reproductive system.

Fu Z ，Kubo T ，Noguchi T ，Kato H ... -  《GROWTH HORMONE & IGF RESEARCH》

Ovarian expression of human insulin-like growth factor-I in transgenic mice results in cyst formation.

Dyck MK ，Parlow AF ，Sénéchal JF ，Sirard MA ，Pothier F ... -  《MOLECULAR REPRODUCTION AND DEVELOPMENT》