S E Samaras

The ovarian insulin-like growth factors, a local amplification mechanism for steroidogenesis and hormone action

The importance of the ovarian insulin-like growth factors (IGFs) has been suggested by data from numerous laboratories and several approaches in the last several years. In the aggregate, these data indicate that this system could function as an important local amplification mechanism for steroidogenesis and gonadotropin action. Studies supporting this hypothesis have described several interacting components of this autocrine/paracrine system. First, the several types of ovarian cells possess an IGF-response system, which includes receptors for IGFs and an effective intracellular transduction system. The IGFs can promote growth and/or differentiation of ovarian cells, and their predominant actions depend on the nature of the cells and the presence of additional modulating factors. The biochemical events leading to enhanced steroidogenesis are now understood in considerable detail and include induction of several steps in the cAMP-dependent steroidogenic cascade. The second component of the ovarian IGF system comprises hormone-responsive local production of IGFs. Both IGF-I and IGF-II may be secreted; gonadotropins, gonadal steroids and locally produced growth factors can regulate the IGF system at this level. Finally, ovarian cells secrete a heterogeneous and complex family of IGF-binding proteins (IGFBPs). These proteins can impact on multiple ovarian functions in a manner which is generally opposite to that of the IGFs themselves. As is the case for the IGFs, the secretion of these proteins by ovarian cells is regulated by gonadotropins and locally produced ovarian factors. Collectively, these several components provide an integrated, synergistically cooperative local network to promote gonadotropin-dependent growth and differentiation in the ovary.

Hemicastration of neonatal boars: hormonal responses and testicular messenger RNA for insulin-like growth factor-I

Abstract The objectives of these studies were to define more completely the hormonal responses of neonatal boars to hemicastration, especially that for inhibin, and to examine the possible involvement of insulin-like growth factor (IGF)-I in steroidogenic compensation by the remaining testis. In Experiment 1, boars were either hemicastrated (HC) or left as intact controls (IC) at 7 days of age. Blood samples were obtained on day 7 and every 4 days thereafter until day 31 when boars were fully castrated. Individual testicular weights of HC boars at day 31 were 86% higher than those for IC boars. Boars in the HC group had higher concentrations of follicle stimulating hormone in plasma and lower concentrations of inhibin than did IC boars, while there was no effect of treatment on concentrations of luteinizing hormone, growth hormone or testosterone. In Experiment 2, boars were HC or left as IC at day 7 and fully castrated at day 9. Blood samples were taken on each day for quantification of testosterone concentrations, and RNA was extracted from day 9-testes for Northern analysis with a probe for IGF-I. There was no difference between treatments for concentrations of testosterone on either day, or for IGF-I mRNA on day 9. However, boars from one litter had greater expression of IGF-I mRNA than did other boars. In conclusion, responses in hormonal secretion following hemicastration of neonatal boars are similar to those in other domestic animals. The compensatory secretion of testosterone in HC boars is apparently not regulated by IGF-I at 2 days following treatment. Further study would determine if IGF-I is involved earlier in the response, or if genetic differences exist in the regulation of testicular IGF-I production.

Ovarian IGF System: Interface with the Gonadotropic and Somatotrophic Axes

This brief chapter outlines the several components of the ovarian insulin-like growth factor (IGF) system and their physiological regulation. Collectively, these data support a critical role for this system in the development and selection of ovarian follicles. Although the role of this system in luteal function is less secure, current evidence also supports a potential role in that ovarian tissue. These data involve descriptive studies in vivo or in vitro that fall short of compelling proof of an obligatory role for locally secreted IGFs in ovarian function in vivo. However, IGF-I gene disruption experiments have now been conducted in transgenic mice (1); further analysis of effects on ovarian function should provide critical missing information in this regard.

Insulin-Like Growth Factors and Their Binding Proteins: Ovarian Modulators of FSH Action

The focus of this chapter is the role of the ovarian insulin-like growth factor (IGF) system as an amplification mechanism for FSH action in the ovarian follicle. Recent data from our own laboratory will be emphasized, although numerous investigators have made important contributions to this area. Collectively, these efforts have established the ovarian IGF system as one of the most persuasive and best documented of the putative ovarian paracrine/ autocrine systems. For the purpose of discussion, it is convenient to divide the IGF system into its intracellular transduction mechanism and its extracellular components (Fig. 15.1), each of which is affected by FSH. The current emphasis in our laboratory is on the extracellular components of the IGF system—locally secreted IGFs and their binding proteins—and this emphasis will be reflected in this paper. However, a brief summary of the actions of IGFs on ovarian cells is appropriate.