LUTEOTROPHIC ACTIONS OF INSULIN-LIKE GROWTH FACTOR-I

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The corpus luteum is the ovarian structure that produces progesterone, a hormone that is essential for the maintenance of pregnancy. The corpus luteum is stimulated to produce progesterone by hormones or factors, called luteotrophins. In the rabbit, the principal luteotrophin is estrogen, produced by the ovarian follicles. From preliminary studies and other information, we propose a new concept for the luteotrophic process in the rabbit: estrogen stimulates the production of insulin-like growth factor-I and/or insulin-like growth factor-II (IGF-I/IGF-II) by luteal cells, and IGF-I/IGF-II then acts in an autocrine or paracrine manner to stimulate metabolism and steroidogenesis by luteal cells. To test this hypothesis, we will use several approaches, each with particular advantage to manipulate the luteotrophic milieu: luteal tissue obtained from estrogen- treated animals, and from normal pseudopregnant and pregnant rabbits; luteal tissue in organ culture; and luteal cells in monolayer culture, in which steroidogenesis is strikingly maintained by IGF-I. Using these approaches, experiments will be conducted to determine: a) whether IGF-I and/or IGF-II, their receptors, and mRNA for IGF-I are expressed in specific cell types of the corpus luteum as revealed by light - and electron - microscopic immunocytochemistry and in situ hybridization; and whether this expression changes with estrogen stimulation and in different stages of the luteal phase and pregnancy as determined by computer-based image analysis and quantitative morphometry; b) whether IGF-I binds to type I or type II receptors, and whether these receptors can be regulated by estrogen, and change during different stages of pseudopregnancy and pregnancy; c) whether IGF-I/IGF-II has a trophic action by producing insulin-like metabolic effects in luteal cells; d) whether steroidogenesis by rabbit luteal tissue is attributable to an autocrine/paracrine action of IGF-I/IGF-II.