Ferasin L, Gabai G, Beattie J, Bono G, Holder A T
Department of Animal Science, Faculty of Veterinary Medicine, Padua, Italy.
J Endocrinol. 1997 Mar;152(3):355-63. doi: 10.1677/joe.0.1520355.
The ability of site-specific antipeptide antisera to enhance the biological activity of ovine FSH (oFSH) in vivo was investigated using hypopituitary Snell dwarf mice. These animals were shown to respond to increasing doses of oFSH (3.3-90 micrograms/day), administered in two daily injections over a 5-day treatment period, in a highly significant dose-dependent fashion. The responses measured were increases in uterine weight, ovarian weight and the index of keratinisation in vaginal smears. The dose-dependent response to oFSH confirmed the suitability of this animal model for these investigations and suggested the suboptimal dose of oFSH (20 micrograms/day) for use in enhancement studies. Five peptides derived from the beta subunit of bovine FSH (bFSH) (A, residues 33-47; B, 40-51; C, 69-80; D, 83-94; E, 27-39) were used to generate polyclonal antipeptide antisera. Of these peptides, only A and B produced an antiserum (raised in sheep) capable of recognising 125I-bFSH in a liquid phase RIA. Antisera prepared against peptide A or peptide B were found to significantly enhance the biological activity of 20 micrograms oFSH/day over a 5-day treatment period. The response to antipeptide antisera alone did not differ significantly from that observed in PBS-injected control animals, neither did the response to FSH alone differ from that observed in animals treated with FSH plus preimmune serum. Thus the enhanced responses are dependent upon the presence of FSH plus antipeptide antiserum. Peptides A and B are located in a region thought to be involved in receptor recognition, this may have implications for the mechanism underlying this phenomenon and/or the structure/function relationships of FSH. That FSH-enhancing antisera can be generated by immunisation of animals with peptides A and B suggests that it may be possible to develop these peptides as vaccines capable of increasing reproductive performance, such as ovulation rate. The high degree of sequence homology between ovine, bovine and porcine (and to a lesser extent human and equine) FSH in the region covered by peptides A and B suggests that these peptides could also be used to promote and regulate ovarian function in all of these species.
利用垂体功能减退的斯内尔侏儒小鼠，研究了位点特异性抗肽抗血清在体内增强绵羊促卵泡素（oFSH）生物活性的能力。这些动物对在5天治疗期内每日分两次注射的递增剂量oFSH（3.3 - 90微克/天）呈现出高度显著的剂量依赖性反应。所测量的反应包括子宫重量增加、卵巢重量增加以及阴道涂片角化指数增加。对oFSH的剂量依赖性反应证实了该动物模型适用于这些研究，并表明在增强研究中使用的oFSH次优剂量为（20微克/天）。从牛促卵泡素（bFSH）的β亚基衍生出五种肽（A，第33 - 47位氨基酸残基；B，第40 - 51位；C，第69 - 80位；D，第83 - 94位；E，第27 - 39位）用于制备多克隆抗肽抗血清。在这些肽中，只有A和B产生了能够在液相放射免疫分析中识别125I - bFSH的抗血清（在绵羊中制备）。发现针对肽A或肽B制备的抗血清在5天治疗期内可显著增强20微克/天oFSH的生物活性。单独对抗肽抗血清的反应与注射PBS的对照动物中观察到的反应无显著差异，单独对FSH的反应与用FSH加免疫前血清处理的动物中观察到的反应也无差异。因此，增强的反应取决于FSH加抗肽抗血清的存在。肽A和B位于被认为与受体识别有关的区域，这可能对该现象的潜在机制和/或FSH的结构/功能关系具有影响。通过用肽A和B免疫动物可产生FSH增强抗血清，这表明有可能将这些肽开发为能够提高生殖性能（如排卵率）的疫苗。在肽A和B覆盖的区域中，绵羊、牛和猪（以及在较小程度上人类和马）的促卵泡素之间具有高度的序列同源性，这表明这些肽也可用于促进和调节所有这些物种的卵巢功能。
