Kennaway D J, Rowe S A
Department of Obstetrics and Gynaecology, University of Adelaide Medical School, South Australia.
J Pineal Res. 1997 Apr;22(3):107-16. doi: 10.1111/j.1600-079x.1997.tb00311.x.
There is increasing evidence that continuous availability of melatonin via implants can produce the same physiological changes in animals as timed administration of the hormone. The mechanisms underlying this apparent contradiction are not known. In an attempt to gain further understanding of the way continuous melatonin administration affects reproductive activity, the effects of melatonin implants on gonadal development and melatonin production were investigated in rats treated neonatally with testosterone. Five-day-old male rats maintained on a 12L:12D photoperiod were injected with 1 mg testosterone propionate to induce photo-responsiveness and implanted at 21 days of age with novel melatonin implants designed to raise the daytime blood melatonin concentration into the nighttime range, i.e., from less than 60 pM in the controls during the day to 380 +/- 33 pM in the implanted rats. Following 21 days treatment, seminal vesicle and ventral prostate weights of implanted rats were significantly less than the controls (27.0 +/- 1.9 vs. 18.5 +/- 1.5 mg/ 100 g BW (P = 0.003) and 33.8 +/- 2.1 vs. 26.7 +/- 2.2 mg/100 g BW (P = 0.02), respectively). To determine the effect of the implants upon melatonin production, urine was collected at hourly intervals during the last four days of the experiment and the hourly 6-sulphatoxymelatonin (aMT.6S) excretion rate was determined. Rats bearing melatonin implants maintained a rhythm of aMT.6S excretion in 12L:12D, which was indistinguishable from that in the control animals except for a raised daytime excretion of the metabolite. Following one cycle of urinary aMT.6S measurements in the light/dark cycle, the animals were released into constant darkness, with the implants still in place or after their removal four hours before darkness to evaluate the characteristics of the melatonin rhythm in the absence of masking effects of the light/dark cycle. The melatonin rhythm persisted in both control and implanted rats and no differences in the onset, offset, or amplitude could be determined. The results of this study indicate that, like many other mammals, for laboratory rats controlled continuous release of melatonin can mimic the effects of short daylength or timed melatonin administration. Despite the reproductive consequences of continuous melatonin delivery, the timing of endogenous melatonin production is unaffected.
越来越多的证据表明，通过植入物持续提供褪黑素，在动物身上能产生与定时注射该激素相同的生理变化。这种明显矛盾背后的机制尚不清楚。为了进一步了解持续给予褪黑素影响生殖活动的方式，我们在新生期用睾酮处理过的大鼠中，研究了褪黑素植入物对性腺发育和褪黑素分泌的影响。将维持在12小时光照：12小时黑暗光周期下的5日龄雄性大鼠注射1毫克丙酸睾酮以诱导光反应性，并在21日龄时植入新型褪黑素植入物，该植入物旨在将白天血液中的褪黑素浓度提高到夜间范围，即从对照组白天低于60皮摩尔提高到植入大鼠的380±33皮摩尔。经过21天的治疗，植入大鼠的精囊和腹侧前列腺重量显著低于对照组（分别为27.0±1.9与18.5±1.5毫克/100克体重，P = 0.003；33.8±2.1与26.7±2.2毫克/100克体重，P = 0.02）。为了确定植入物对褪黑素分泌的影响，在实验的最后四天每隔一小时收集尿液，并测定每小时6 - 硫酸氧基褪黑素（aMT.6S）的排泄率。植入褪黑素的大鼠在12小时光照：12小时黑暗条件下维持aMT.6S排泄节律，除了该代谢物白天排泄量增加外，与对照动物的节律没有区别。在光/暗周期中进行一轮尿液aMT.6S测量后，将动物置于持续黑暗中，植入物仍在位或在黑暗前四小时取出，以评估在没有光/暗周期掩盖效应的情况下褪黑素节律的特征。对照组和植入组大鼠的褪黑素节律均持续存在，且在开始、结束或幅度方面未发现差异。本研究结果表明，与许多其他哺乳动物一样，对于实验室大鼠，控制褪黑素的持续释放可以模拟短日照或定时给予褪黑素的效果。尽管持续给予褪黑素会对生殖产生影响，但内源性褪黑素分泌的时间不受影响。
