Herbert C A, Trigg T E, Renfree M B, Shaw G, Eckery D C, Cooper D W
Department of Biological Sciences, Macquarie University, North Ryde, New South Wales 2109, Australia.
Biol Reprod. 2004 Jun;70(6):1836-42. doi: 10.1095/biolreprod.103.025122. Epub 2004 Feb 18.
This study evaluated the potential of slow-release GnRH agonist (deslorelin) implants to inhibit reproductive function in the male tammar wallaby. The specific aim was to measure the effects of graded dosages of deslorelin on testes size and plasma LH and testosterone concentrations. Adult male tammar wallabies were assigned to four groups (n = 6 per group) and received the following treatment: control, placebo implant; low dose, 5 mg deslorelin; medium dose, 10 mg; high dose, 20 mg. All dosages of deslorelin induced acute increases (P < 0.001) in plasma LH and testosterone concentrations within 2 h, with concentrations remaining elevated during the first 24 h but returning to pretreatment levels by Day 7. Thereafter, there was no evidence of a treatment-induced decline in plasma testosterone concentrations. There was no detectable difference in basal LH concentrations between treated and control animals, nor was there a significant change in testes width or length (P > 0.05). These results suggest that the male tammar wallaby is resistant to the contraceptive effects of chronic GnRH agonist treatment. Despite the maintenance of testosterone secretion, the majority of male tammars (10 of 17) failed to respond to a GnRH challenge with a release of LH between Days 186 and 197 of treatment. The failure of animals to respond to exogenous GnRH suggests a direct effect of deslorelin on the pituitary, resulting in a level of desensitization that was sufficient to inhibit a LH surge but insufficient to inhibit basal LH secretion. The variation between animals is believed to result from earlier recovery of some individuals, in particular those that received a lower dose, or individual resistance to the desensitization process.
本研究评估了缓释促性腺激素释放激素（GnRH）激动剂（地洛瑞林）植入物抑制雄性帚尾袋貂生殖功能的潜力。具体目标是测量不同剂量地洛瑞林对睾丸大小以及血浆促黄体生成素（LH）和睾酮浓度的影响。成年雄性帚尾袋貂被分为四组（每组n = 6），并接受以下处理：对照组，植入安慰剂；低剂量组，5毫克地洛瑞林；中剂量组，10毫克；高剂量组，20毫克。所有剂量的地洛瑞林均在2小时内引起血浆LH和睾酮浓度急性升高（P < 0.001），浓度在最初24小时内保持升高，但到第7天时恢复到预处理水平。此后，没有证据表明处理导致血浆睾酮浓度下降。处理组和对照组动物的基础LH浓度没有可检测到的差异，睾丸宽度或长度也没有显著变化（P > 0.05）。这些结果表明，雄性帚尾袋貂对慢性GnRH激动剂处理的避孕作用具有抗性。尽管维持了睾酮分泌，但大多数雄性帚尾袋貂（17只中的10只）在治疗的第186天至197天之间对GnRH刺激未出现LH释放反应。动物对外源性GnRH无反应表明地洛瑞林对垂体有直接作用，导致脱敏程度足以抑制LH激增，但不足以抑制基础LH分泌。动物之间的差异被认为是由于一些个体（特别是接受较低剂量的个体）恢复较早，或者是个体对脱敏过程具有抗性所致。
