Parker P A, Coffman E A, Pohler K G, Daniel J A, Aucagne V, Beltramo M, Whitlock B K
College of Veterinary Medicine, University of Tennessee, Knoxville, TN, USA.
School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA.
Theriogenology. 2019 May;130:111-119. doi: 10.1016/j.theriogenology.2019.03.002. Epub 2019 Mar 6.
Kisspeptin (KP) is a neuropeptide integral in regulating puberty and gonadotropin releasing hormone. Compound 6 (C6), a KP analog, is more potent in vitro, has a longer half-life, and may have greater therapeutic applications than KP. To determine the acute and subacute effects of KP and C6 on serum concentrations of luteinizing hormone (LH), follicle stimulating hormones (FSH), and testosterone (T), prepubertal bull calves [12.1 ± 1.1 (SD) weeks of age; 91.2 ± 10.8 kg BW] were assigned to one of three treatment groups [Saline (n = 4), KP (n = 4; 20 nmoles), or C6 (n = 4; 20 nmoles). Treatments were administered intramuscularly once daily for four consecutive days. Blood samples were collected every 15 min for 6 h immediately following treatment administration on Day 1 (acute) and Day 4 (subacute). Serum concentrations of LH, FSH, and T were determined by radioimmunoassay. For each day, effects of treatment, time, and interactions on LH and FSH concentrations and pulse parameters were analyzed using procedures for repeated measures with JMP Software (SAS Inst. Inc., Cary, NC). There was a treatment × time interaction during Day 1 (P < 0.0001) and Day 4 (P = 0.02) such that LH concentrations were greatest following administration of C6 (albeit diminished during Day 4). Number of LH pulses were least (P = 0.02) and LH nadirs were highest (P = 0.04) following administration of C6 (P = 0.02). There was no effect of treatment (P = 0.95) or treatment × time interaction (P = 0.10) on serum FSH concentrations during Day 1. During Day 4 FSH concentrations (P = 0.02) and number of FSH pulses (P = 0.02) were least following administration of C6. There was no effect of treatment (P = 0.33), time (P = 0.19) or treatment × time interaction (P = 0.44) on T concentrations. In conclusion, acute and subacute C6 increased LH concentrations and subacute C6 decreased FSH concentrations and pulse parameters. Despite suppression of FSH with subacute daily administration of C6, altered frequency and timing of treatment with KP analogs may have application to affect the onset of puberty in livestock.
亲吻素（KP）是一种在调节青春期和促性腺激素释放激素方面不可或缺的神经肽。化合物6（C6）作为一种KP类似物，在体外活性更强，半衰期更长，并且可能比KP具有更大的治疗应用价值。为了确定KP和C6对促黄体生成素（LH）、促卵泡生成素（FSH）和睾酮（T）血清浓度的急性和亚急性影响，将青春期前的公牛犊[年龄12.1±1.1（标准差）周；体重91.2±10.8千克]分配到三个治疗组之一[生理盐水组（n = 4）、KP组（n = 4；20纳摩尔）或C6组（n = 4；20纳摩尔）]。连续四天每天一次肌肉注射给药。在第1天（急性）和第4天（亚急性）给药后立即每15分钟采集一次血样，共采集6小时。通过放射免疫测定法测定血清中LH、FSH和T的浓度。对于每一天，使用JMP软件（SAS公司，北卡罗来纳州卡里）的重复测量程序分析治疗、时间以及它们之间的相互作用对LH和FSH浓度及脉冲参数的影响。在第1天（P < 0.0001）和第4天（P = 0.02）存在治疗×时间的相互作用，使得在给予C6后LH浓度最高（尽管在第4天有所下降）。给予C6后LH脉冲次数最少（P = 0.02）且LH最低点最高（P = 0.04）（P = 0.02）。在第1天，治疗对血清FSH浓度没有影响（P = 0.95），治疗×时间的相互作用也无影响（P = 0.10）。在第4天，给予C6后FSH浓度（P = 0.02）和FSH脉冲次数（P = 0.02）最少。治疗对T浓度没有影响（P = 0.33），时间（P = 0.19）以及治疗×时间的相互作用也无影响（P = 0.44）。总之，急性和亚急性给予C6可提高LH浓度，亚急性给予C6可降低FSH浓度和脉冲参数。尽管亚急性每日给予C6会抑制FSH，但改变KP类似物的给药频率和时间可能会应用于影响家畜青春期的开始。
