Morley P, Calaresu F R, Barbe G J, Armstrong D T
Department of Physiology, University of Western Ontario, London, Canada.
Biol Reprod. 1989 Apr;40(4):735-43. doi: 10.1095/biolreprod40.4.735.
It has been shown recently that insulin enhances differentiation of rat, pig, and human granulosa cells. The present studies were done to determine if insulin also plays a role in the regulation of theca cell steroidogenesis. Theca cells were obtained from prepubertal gilts and cultured under serum-free conditions for 48 h. Theca cell androstenedione production under basal and luteinizing hormone (LH)-stimulated conditions was significantly increased by adding insulin (1 microgram/ml) to the culture medium. Treatment of basal and LH-stimulated cultures with increasing concentrations of insulin (0.001-10 micrograms/ml) caused dose- and time-dependent increments in androstenedione production, but the effect was independent of the dose of LH employed. The ability of insulin to enhance thecal cell androstenedione production was mimicked by somatomedin C, but not by relaxin. Studies to determine the mechanism(s) of action of insulin showed that insulin action is exerted, at least in part, at a site(s) proximal to cyclic adenosine 3'5'-monophosphate (cAMP) generation, since insulin enhanced both basal and LH-stimulated accumulation of extracellular cAMP in addition to increasing androstenedione production. This effect was further enhanced by 3-isobutyl-1-methyl xanthine, an inhibitor of phosphodiesterase activity. Insulin treatment also caused dose-dependent increments in forskolin- and prostaglandin E2-stimulated accumulation of extracellular cAMP and androstenedione. Insulin also increased both the basal and LH-stimulated production of progesterone and its precursor pregnenolone, in addition to the increases in androstenedione.(ABSTRACT TRUNCATED AT 250 WORDS)
最近研究表明，胰岛素可促进大鼠、猪和人颗粒细胞的分化。本研究旨在确定胰岛素是否也在卵泡膜细胞甾体激素生成的调节中发挥作用。从青春期前的小母猪获取卵泡膜细胞，并在无血清条件下培养48小时。向培养基中添加胰岛素（1微克/毫升）可显著增加基础状态和促黄体生成素（LH）刺激条件下卵泡膜细胞雄烯二酮的生成。用浓度递增的胰岛素（0.001 - 10微克/毫升）处理基础状态和LH刺激的培养物，可导致雄烯二酮生成呈剂量和时间依赖性增加，但该效应与所使用的LH剂量无关。胰岛素增强卵泡膜细胞雄烯二酮生成的能力可被生长调节素C模拟，但不能被松弛素模拟。确定胰岛素作用机制的研究表明，胰岛素作用至少部分是在环磷酸腺苷（cAMP）生成近端的位点发挥的，因为胰岛素除了增加雄烯二酮生成外，还增强了基础状态和LH刺激下细胞外cAMP的积累。磷酸二酯酶活性抑制剂3 - 异丁基 - 1 - 甲基黄嘌呤可进一步增强该效应。胰岛素处理还导致福斯可林和前列腺素E2刺激的细胞外cAMP和雄烯二酮积累呈剂量依赖性增加。除了增加雄烯二酮生成外，胰岛素还增加了基础状态和LH刺激下孕酮及其前体孕烯醇酮的生成。（摘要截短于250字）
