Role of IGF-I and IGF Binding Proteins in Regulation of Human Ovarian Function

1)IGF-I及其结合蛋白在人卵巢颗粒细胞分泌雌二醇中的作用IGF-I以剂量依赖的方式刺激体外受精-胚胎移植（IVF-ET）患者卵巢颗粒细胞分泌雌二醇。IGFBP-1和IGFBP-3不影响E2的基础分泌，但IGFBP_s可抑制IGF-1刺激的E2分泌，IGFBP-1和IGFBP-3均抑制IGF<125>-1与膜受体的结合。这些结果提示，IGFBP_s可能是卵巢中IGF-I作用的调节剂，IGFBP_s通过抑制IGF-I与其受体的结合而抑制IGF-I刺激的E_2释放。2）IGF-I系统介导的FSH对人颗粒细胞的作用为了评价FSH对人颗粒细胞分泌IGFBP_s的调节作用，将人颗粒细胞与FSH或不与FSH孵育。 ...更多信息 艾德呈剂量依赖性抑制IGFBP-1的分泌。FSH不抑制IGFBP-3的分泌，但抑制IGFBP-3的结合活性。为了评估蛋白酶活性，将β <125>I-IGFBP-3与培养基一起孵育。结果<125>表明，FSH通过抑制IGFBP-1的分泌，促进IGFBP-3的蛋白水解，从而增强IGF-I的作用。3）IGF-I和IGFBP-3的生理意义为了解闭锁患者卵泡发育过程中卵泡内环境的变化，测定了不同卵泡液中类固醇激素、IGF-I和IGFBPs的含量。雄烯二酮（A）与E2的比值在闭锁卵泡中大于10.0，在成熟卵泡中小于0.1。闭锁卵泡中IGF-I水平显著低于成熟卵泡（P&lt;0.05），IGFBP-2和IGFBP-4结合活性显著高于成熟卵泡（P &lt;0.05）。因此，闭锁卵泡高A、低E2的卵泡内环境的形成可能与通过刺激IGFBP-2和-4的结合活性来抑制IGF-I的生物学活性有关。少

1) Role of IGF-I and IGF binding proteins in estradiol secretion by human luteinizing graunlosa cells.IGF-I stimulated the secretion of E2 in a dose dependent fashion by human luteinizing granulosa cells which were collected from the patients under IVF-ET program. While IGFBP-1 and -3 did not influence the basal secretion of E2, the same amount of IGFBP_s reduced the secretion of E2 stimulated by IGF-I.Both IGFBP-1 and -3 inhibited ^<125>I-IGF-I binding to membrane receptors. These data suggested that IGFBP_s might be aregulator of IGF-I actionin the ovary and inhibitory effects of IGFBP_s on IGF-I-stimulated E2 release were achieved by inhibiting IGF-I binding to its receptors.2) IGF-I system-mediated FSH action on human granulosa cellsAddition of IGF-I with FSH highly stimulated the secretion of E2 by human luteinizing granulosa cells. To evaluate the regulation of the secretion of IGFBP_s by FSH in human granulosacells, granulosacells were in cubated with or without FSH.FSH in hibit … More ed the secretion of IGFBP-1 dose dependently. FSH did not in hibit the secretion of immunore active IGFBP-3, but inhibited the binding activity of IGFBP-3 evaluated by Westem ligandblot. To assess the protease activity, ^<125>I-IGFBP-3 was in cubated with the cultured medium. ^<125>I-IGFBP-3 degraded into small fragments when it was in cubated with the cultured medium treated with FSH.These data suggested that FSH enhances the action of IGF-I in human granulosa cells by in hibiting the secretion of IGFBP-1 and the binding activity of IGFBP-3 by stimulating the proteolysis of IGFBP-3.3) Physiological significance of IGF-I and IGFBP_s in follicular development and atresia.To evaluate the change of intrafollicular environment according to follicle growth of atresia, levels of steroid hormones and IGF-I and IGFBP_s in the follicular fluid of various follicles, which were collected from patients under laparotomies, were measured. The ratio of androstenedione (A) to E2 was more than 10.0 in atretic follicles and less than 0.1 in mature follicles. In atretic follicles levels of IGF-I were significantly lower (P<0.05), moreober, binding activities of IGFBP-2 and -4 were higher, compared to those in mature follicles whose IGFBP-4 proteolysis was accerelated. Taken together, formation of the intrafollicular environment as high A and low E2 of atretic follicles might have relationship with the system of suppressing the biological activities of IGF-I via stimulating the binding activities of IGFBP-2 and -4. Less