A test of the coincidence and duration models of melatonin action in Siberian hamsters: the effects of 1‐hr melatonin infusions on testicular development in intact and pinealectomized prepubertal Phodopus sungorus

Abstract

The pineal hormone melatonin is known to play an important role in mediating photoperiodic messages to the reproductive system in seasonal breeding animals. Our goal was to test, in a single experimental paradigm, two hypotheses that have been forwarded to describe how the circadian rhythm of pineal melatonin transmits photoperiodic information to the reproductive system: 1) induction, i.e., a short-day effect, occurs when secreted melatonin and a circadian rhythm of sensitivity to melatonin coincide in time; 2) induction occurs following exposure to elevated circulating melatonin levels for a prescribed duration. In order to determine the relative validity of these hypotheses, we investigated the testicular maturation response to 1-hr daily infusions of 10, 25, and 50 ng of melatonin in pinealectomized intact and prepubertal Siberian hamsters (Phodopus sungorus). Animals received, beginning on day 15 of life, programmed subcutaneous infusions of melatonin or vehicle at one of five time points (19:00-20:00, 20:00-21:00, 21:00-22:00, 24:00-01:00, and 03:00-04:00 hr) for 15 days. In animals gestated and raised in a long photoperiod (LD16:8 = 16L, where L is the duration of light in hours, and D that of dark), melatonin infusion right after lights off (20:00-21:00 hr) significantly retarded gonadal maturation; this dose was ineffective at other times tested. Doses of 10 and 25 ng melatonin were ineffective at all time points. Identical results were obtained in prepubertal hamsters gestated in a short photoperiod (LD10:14 = 10L) and raised in 16L; these results were independent of the presence or absence of the pineal gland. In animals gestated and raised in 10L, melatonin infusions failed to suppress testicular development beyond that induced by the photoperiod; testicular development was maximally suppressed in all groups. The results of these investigations are best explained under the experimental conditions employed here: 1) the photoperiodic gonadal response in juvenile Siberian hamsters is regulated by the coincidence in time of exogenously administered melatonin with an intrinsic rhythm of sensitivity to melatonin, which, under the constraints imposed by our experimental design, occurred at 20:00-21:00 hr; and 2) the duration of the melatonin signal alone, equal in all groups, cannot explain the results.

Like melatonin, agomelatine (S20098) increases the amplitude of oscillations of two clock outputs: melatonin and temperature rhythms

“…In addition, we confirm that rhythmic effects of the drugs are dose dependent (Gunduz & Stetson, 2001). However, MLT has an effect at lower doses (1 mg/kg) than Ago (5 mg/kg), which could be explained by the dual melatoninergic agonist and serotoninergic antagonist properties of Ago, which thus requires higher doses for rhythmic effects.…”

“…*p50.05 and ***p50.001. effect during a specific time window, only when infused late in the afternoon while endogenous MLT is low (Gunduz & Stetson, 2001). Under our experimental conditions (LD 12:12), our results show that a single injection of Ago or MLT at the end of the day is sufficient to increase the duration of the MLT endogenous peak (equivalent to the short photoperiod signal) on 2 consecutive days.…”

Photoperiodic time measurement and seasonal immunological plasticity

“…The information extracted from a melatonin-based day length signal by the reproductive neuroendocrine system is based entirely upon the duration of the signal. Neither the amplitude of the MEL signal nor the circadian phase during which it occurs has any bearing on its interpretation by systems that regulate reproductive condition (Goldman et al, 1984; Gorman, 2003; but see Gunduz & Stetson, 2001 for a challenge to this hypothesis). Gonadal recrudescence (redevelopment) occurs after 4–5 months of exposure to short days (Reiter, 1972); this is likely triggered by an interval timing mechanism that is associated with the development of refractoriness to inhibitory MEL signals (Bittman, 1978; Freeman & Zucker, 2001).…”

Weak evidence of bright light effects on human LH and FSH

“…There is a preponderance of evidence that light at night functions to decrease the duration of melatonin secretion, causing the nights to be interpreted as shorter (complementing a longer summer-like day) [6-8]. However, some evidence for critical time intervals for light (or melatonin) sensitivity at night suggests a more complex mechanism [9,10]. Moreover, in hamsters, light may stimulate LH at times outside the normal interval of melatonin secretion [4].…”