Adashi E Y, Resnick C E, Hurwitz A, Ricciarelli E, Hernandez E R, Rosenfeld R G
Division of Reproductive Endocrinology, University of Maryland School of Medicine, Baltimore 21201.
Endocrinology. 1991 Feb;128(2):754-60. doi: 10.1210/endo-128-2-754.
Recent observations disclosed the multiplicity of granulosa cell-derived high affinity insulin-like growth factor binding proteins (IGFBPs) and revealed the striking ability of high doses of FSH to suppress their constitutive release under both in vitro and in vivo circumstances. It is the objective of this communication to characterize in greater detail the modulatory effect(s) exerted by FSH on the elaboration of IGFBPs by granulosa cells from immature, estrogen-primed rats. The ability of FSH to regulate the elaboration of granulosa cell-derived IGFBPs proved dose-dependent but biphasic in nature. Specifically, FSH concentrations in the range of 1-3 ng/ml applied for 72 h produced a significant (P less than 0.05) increase in polyethylene glycol-precipitable [125I]IGF-I binding activity corresponding to all IGFBP species detectable by ligand blotting. In contrast, treatment with higher concentrations (greater than or equal to 10 ng/ml) of FSH resulted in progressive dose-dependent inhibition of the constitutive release of IGF-I binding activity (80% inhibition at the 100 ng/ml dose level) and the virtual elimination of all detectable IGFBP species. Time-course studies disclosed a significant (P less than 0.05) initial (apparent at the 24-h time point) stimulatory effect of a high dose of FSH (100 ng/ml) corresponding mostly (but not solely) to the single minor (23K) IGFBP band. In contrast, more prolonged exposure to FSH (greater than or equal to 48 h) produced progressive time-dependent decrements in IGF-I binding activity, an effect associated with a decrease in the relative representation of the major band doublet (28-29K), the 23K species being all but eliminated under these experimental circumstances. Hypophysectomy produced significant (P less than 0.05) inhibition of the subsequent in vitro release of granulosa cell-derived precipitable IGF-I binding activity strongly suggesting that (presumptively stimulatory) pituitary principles other than FSH are likely involved in the regulation of granulosa cell IGFBP release and that the trophic influence of these putative agents appears to outweight the potential disinhibition of FSH hormonal action. Taken together, these findings indicate that the pituitary regulation of granulosa cell-derived IGFBPs is complex and is not FSH-exclusive. Our findings further indicate that the ability of FSH to regulate granulosa cell-derived IGFBPs is dose- and time-dependent but biphasic in nature, an effect characterized by an early low-dose stimulatory effect and a late high-dose inhibitory effect.(ABSTRACT TRUNCATED AT 400 WORDS)
最近的观察结果揭示了颗粒细胞衍生的高亲和力胰岛素样生长因子结合蛋白（IGFBPs）的多样性，并显示出高剂量促卵泡激素（FSH）在体外和体内环境下均具有显著抑制其组成性释放的能力。本通讯旨在更详细地描述FSH对未成熟、经雌激素预处理大鼠颗粒细胞产生IGFBPs的调节作用。FSH调节颗粒细胞衍生IGFBPs产生的能力呈剂量依赖性，但本质上具有双相性。具体而言，1 - 3 ng/ml范围内的FSH浓度作用72小时，可使聚乙二醇沉淀的[125I]IGF-I结合活性显著（P < 0.05）增加，该活性对应于配体印迹法可检测到的所有IGFBP种类。相反，用更高浓度（≥10 ng/ml）的FSH处理会导致IGF-I结合活性的组成性释放逐渐出现剂量依赖性抑制（在100 ng/ml剂量水平时抑制80%），并且几乎消除所有可检测到的IGFBP种类。时间进程研究显示，高剂量FSH（100 ng/ml）具有显著（P < 0.05）的初始（在24小时时间点明显）刺激作用，主要（但非唯一）对应于单一的次要（23K）IGFBP条带。相反，长时间暴露于FSH（≥48小时）会使IGF-I结合活性随时间逐渐下降，这种效应与主要条带双峰（28 - 29K）相对含量的减少相关，在这些实验条件下，23K种类几乎被消除。垂体切除显著（P < 0.05）抑制了随后颗粒细胞衍生的可沉淀IGF-I结合活性的体外释放，这强烈表明除FSH外，（推测具有刺激作用的）垂体因子可能参与了颗粒细胞IGFBP释放的调节，并且这些假定因子的营养作用似乎超过了FSH激素作用的潜在去抑制作用。综上所述，这些发现表明垂体对颗粒细胞衍生IGFBPs的调节是复杂的，并非仅由FSH介导。我们的研究结果进一步表明，FSH调节颗粒细胞衍生IGFBPs的能力呈剂量和时间依赖性，但本质上具有双相性，其特点是早期低剂量刺激作用和晚期高剂量抑制作用。（摘要截选至400字）
