Grasso P, Rozhavskaya M, Reichert L E
Department of Biochemistry and Molecular Biology A-10, Albany Medical College, New York 12208, USA.
Biol Reprod. 1998 Mar;58(3):821-5. doi: 10.1095/biolreprod58.3.821.
We have previously reported that a synthetic peptide corresponding to amino acid residues 81-95 of the human (h) FSH-beta subunit inhibited binding of [125I]hFSH to bovine calf testis membranes and stimulated estradiol biosynthesis in primary cultures of rat Sertoli cells. We have now obtained several lines of evidence demonstrating in vivo effects of hFSH-beta-(81-95) on the mouse estrous cycle. 1) A single i.p. injection of 200 micrograms/g BW hFSH-beta-(81-95) significantly (p < 0.001) prolonged vaginal estrus in comparison to that in vehicle-injected control mice. 2) Vaginal smears taken at estrus from mice given hFSH-beta-(81-95) were characterized by the complete absence of epithelial casts, a hallmark of spontaneous ovulation in mice. 3) Mice receiving hFSH-beta-(81-95) had significantly (p < 0.001) lower serum estradiol at proestrus and serum progesterone at diestrus than vehicle-injected control mice. 4) The proestrous effects of estrogen on uterine ballooning and weight gain, clearly evident in vehicle-injected control mice, were not observed in mice treated with hFSH-beta-(81-95). A synthetic peptide corresponding to the carboxy-terminal region of hFSH-beta-(81-95), hFSH-beta-(90-95), inhibited binding of [125I]hFSH to bovine calf testis membranes, antagonized FSH-stimulated estradiol biosynthesis by primary cultures of rat Sertoli cells, and prolonged vaginal estrus in normally cycling mice. A synthetic peptide corresponding to the amino-terminal domain, hFSH-beta-(81-86), was inactive in vitro and had no effect on the mouse estrous cycle. The results of the present study provide additional evidence for in vivo effects of FSH-related synthetic peptides.
我们之前报道过，一种与人类（h）促卵泡激素β亚基第81 - 95位氨基酸残基对应的合成肽可抑制[125I]hFSH与牛犊睾丸膜的结合，并刺激大鼠支持细胞原代培养物中雌二醇的生物合成。我们现在已获得多项证据，证明hFSH-β-(81 - 95)对小鼠发情周期有体内效应。1）与注射溶剂的对照小鼠相比，腹腔注射200微克/克体重的hFSH-β-(81 - 95)可显著（p < 0.001）延长阴道发情期。2）在发情期从小鼠采集的阴道涂片显示完全没有上皮细胞脱落物，这是小鼠自发排卵的一个标志。3）接受hFSH-β-(81 - 95)的小鼠在动情前期的血清雌二醇和动情后期的血清孕酮水平显著（p < 0.001）低于注射溶剂的对照小鼠。4）在注射溶剂的对照小鼠中明显可见的雌激素对子宫膨胀和体重增加的动情前期效应，在用hFSH-β-(81 - 95)处理的小鼠中未观察到。一种与hFSH-β-(81 - 95)羧基末端区域对应的合成肽，hFSH-β-(90 - 95)，可抑制[125I]hFSH与牛犊睾丸膜的结合，拮抗大鼠支持细胞原代培养物中FSH刺激的雌二醇生物合成，并延长正常发情周期小鼠的阴道发情期。一种与氨基末端结构域对应的合成肽，hFSH-β-(81 - 86)，在体外无活性，对小鼠发情周期无影响。本研究结果为FSH相关合成肽的体内效应提供了更多证据。
