CONTROLLED-RELEASE MELATONIN IMPLANTS DELAY PUBERTY IN RATS WITHOUT ALTERING MELATONIN RHYTHMICITY

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 a pparent contradiction are not known. In an attempt to gain further und erstanding of the way continuous melatonin administration affects repr oductive activity, the effects of melatonin implants on gonadal develo pment and melatonin production were investigated in rats treated neona tally with testosterone. Five-day-old male rats maintained on a 12L:12 D photoperiod were injected with 1 mg testosterone propionate to induc e photo-responsiveness and implanted at 21 days of age with novel mela tonin implants designed to raise the daytime blood melatonin concentra tion into the nighttime range, i.e., from less than 60 pM in the contr ols during the day to 380 +/- 33 pM in the implanted rats. Following 2 1 days treatment, seminal vesicle and ventral prostate weights of impl anted rats were significantly less than the controls (27.0 +/- 1.9 vs. 18.5 +/- 1.5 mg/100g BW (P = 0.003) and 33.8 +/- 2.1 vs. 26.7 +/- 2.2 mg/100g BW (P = 0.02), respectively). To determine the effect of the implants upon melatonin production, urine was collected at hourly inte rvals during the last four days of the experiment and the hourly 6-sul phatoxymelatonin (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 f or a raised daytime excretion of the metabolite. Following one cycle o f urinary aMT.6S measurements in the light/dark cycle, the animals wer e released into constant darkness, with the implants still in place or after their removal four hours before darkness to evaluate the charac teristics 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 amplitu de 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 melaton in administration. Despite the reproductive consequences of continuous melatonin delivery, the timing of endogenous melatonin production is unaffected.