Armstrong J D, Stanko R L, Cohick W S, Simpson R B, Harvey R W, Huff B G, Clemmons D R, Whitacre M D, Campbell R M, Heimer E P
Department of Animal Science, College of Agriculture and Life Sciences, North Carolina State University, Raleigh.
J Physiol Pharmacol. 1992 Dec;43(4 Suppl 1):179-93.
We have utilized active immunization against growth hormone releasing factor (GRF) to investigate relationships among somatotropin (ST), insulin-like growth factor-I (IGF-I), IGF binding proteins (IGFBP) and ovarian function in heifers. Active immunization against GRF (GRFi) has been demonstrated to abolish episodic release of ST and decrease serum concentrations of IGF-I. In initial experiments investigating onset of puberty, breeds of heifers differing in growth rate and reproductive traits (Angus, Charolais and Simmental) were immunized against GRF or served as controls (immunized against carrier protein, human serum albumin, HSAi). GRFi decreased rate of muscle and skeletal growth, but increased deposition of adipose tissue. In Angus and Charolais, but not Simmental heifers, GRFi at 6 mo of age significantly delayed onset of puberty beyond 18 mo of age. Retrospective analyses of serum IGF-I revealed that GRFi heifers reaching puberty at a normal age had greater pre-treatment (6 mo of age) IGF-I than GRFi heifers in which puberty was delayed. Collectively, these results strongly indicate that the bovine hypothalamic-hypophyseal-ovarian axis is particularly sensitive to changes in metabolism at or near 6 mo of age. Another series of experiments tested the hypothesis that lowering serum IGF-I via GRFi initially at 3 mo of age would increase the percentage of Angus and Simmental heifers not reaching puberty. Three mo old Angus and Simmental heifers were assigned to GRFi (n = 18), HSAi (n = 14) or received no treatment (controls, n = 16). HSAi and GRFi heifers were unilaterally ovariectomized (ULO) at 6 mo of age. As anticipated, GRFi at a younger age increased percentage of heifers not reaching puberty; over 75% of control and HSAi heifers reached puberty by 14 mo of age compared to 22% of GRFi heifers. Serum and follicular fluid (FFL; follicles < or = 4 mm) concentrations of IGF-I were suppressed by GRFi. Serum, but not FFL concentrations of IGF binding protein-2 (IGFBP-2) were greater in GRFi than in HSAi heifers. GRFi delayed puberty apparently by suppressing follicular growth because number of follicles < or = 7 mm was significantly lower in GRFi than in HSAi heifers. In conclusion, active immunization against GRF at 3 or 6 months of age delays puberty in beef heifers. Delayed puberty was preceded by suppression of follicular growth, and decreased concentrations of IGF-I in serum and follicular fluid.(ABSTRACT TRUNCATED AT 400 WORDS)
我们利用针对生长激素释放因子（GRF）的主动免疫来研究小母牛中生长激素（ST）、胰岛素样生长因子-I（IGF-I）、IGF结合蛋白（IGFBP）与卵巢功能之间的关系。已证明针对GRF的主动免疫（GRFi）可消除ST的脉冲式释放并降低IGF-I的血清浓度。在最初研究青春期开始的实验中，对生长速度和繁殖性状不同的小母牛品种（安格斯牛、夏洛来牛和西门塔尔牛）进行了针对GRF的免疫或作为对照（针对载体蛋白人血清白蛋白进行免疫，HSAi）。GRFi降低了肌肉和骨骼生长速度，但增加了脂肪组织的沉积。在安格斯牛和夏洛来牛中，但在西门塔尔牛中未出现这种情况，6月龄时进行GRFi显著延迟了青春期开始时间，超过18月龄。对血清IGF-I的回顾性分析显示，正常年龄进入青春期的GRFi小母牛在预处理（6月龄）时的IGF-I水平高于青春期延迟的GRFi小母牛。总体而言，这些结果有力地表明，牛的下丘脑 - 垂体 - 卵巢轴在6月龄或接近6月龄时对代谢变化特别敏感。另一系列实验检验了这样的假设，即最初在3月龄时通过GRFi降低血清IGF-I会增加未进入青春期的安格斯牛和西门塔尔牛小母牛的比例。将3月龄的安格斯牛和西门塔尔牛小母牛分为GRFi组（n = 18）、HSAi组（n = 14）或不进行处理（对照组，n = 16）。HSAi组和GRFi组小母牛在6月龄时进行单侧卵巢切除（ULO）。正如预期的那样，较年轻时进行GRFi增加了未进入青春期的小母牛比例；超过75%的对照组和HSAi组小母牛在14月龄时进入青春期，而GRFi组小母牛只有22%。GRFi抑制了血清和卵泡液（FFL；卵泡≤4mm）中IGF-I的浓度。GRFi组小母牛血清中IGF结合蛋白-2（IGFBP-2）的浓度高于HSAi组，但卵泡液中的浓度并非如此。GRFi显然通过抑制卵泡生长延迟了青春期，因为GRFi组中≤7mm卵泡的数量显著低于HSAi组。总之，3或6月龄时针对GRF的主动免疫会延迟肉用小母牛的青春期。青春期延迟之前先出现卵泡生长受抑制，以及血清和卵泡液中IGF-I浓度降低。（摘要截断于400字）
