Could long-term administration of melatonin to prepubertal children affect timing of puberty? A clinician’s perspective

Figures & data

Figure 1 Interaction of hypothalamic factors and peripheral signals on puberty onset.

Notes: Republished with permission of Wolters Kluwer Health, from Control of the onset of puberty, Livadas S, Chrousos GP, volume 28(4), 2016; permission conveyed through Copyright Clearance Center, Inc.⁴⁷ Schematic presentation of the highly specialized complex comprised of KNDy and GnRH neurons, and pituitary gonadotropes regulating pubertal onset. The integral function of KNDy neurons (with their auto regulatory loops) and GnRH neurons is depicted, as this pertains to gonadotropin secretion. The effects of positive and negative stimuli on this complex are presented with red and green arrows respectively. Energy sensing, hormones, epigenetic processes, and endocrine disruptors participate in the process.

Table 1 Examples of the effects of exogenous melatonin administration on the timing of puberty in lambs, gilts, rats, and male Siberian hamsters

Study	Procedure	Mammal	Timing of puberty
Recabarren et al (1998)^Citation74	Exogenous melatonin (oral)	Ewe lamb	Advanced
Kennaway et al (1986)^Citation73	Exogenous melatonin (implant)	Ewe lamb	Delayed
Kennaway et al (1985)^Citation75	Pinealectomy	Ewe lamb	Delayed
Kennaway et al (2015)^Citation72	Exogenous melatonin (implant)	Gilt (pig)	No change
Kennaway (1997)^Citation97	Exogenous melatonin (implant)	Rat	Delayed
Buchanan et al (1991)^Citation71	Exogenous melatonin (injection)	Djungarian (Siberian) hamster	Arrested

Note: Extensive literature exists about changes in sexual behavior in seasonally breeding mammals by manipulation of the photoperiod, which is beyond the scope of this narrative review (additional information can be found elsewhere).^61–64

Figure 2 Working model indicating how the photo-inhibitory melatonergic message in short day conditions is integrated in the hypothalamus to further regulate the gonadotropic axis in the male Syrian hamster.

Notes: Photo-inhibitory melatonergic message in male Syrian hamster. Reproduced with permission from Simonneaux et al, 2013.⁷⁸

LivadasSChrousosGPControl of the onset of pubertyCurr Opin Pediatr201628455155827386974

 PubMed Web of Science ®Google Scholar

RecabarrenSELobosAHenriquezJPeneipilCPariloJEffect of daily melatonin treatment on the profile of luteinizing hormone secretion in prepubertal ewesAgrociencia19981430315

 Google Scholar

KennawayDJPeekJCGilmoreTARoylesPPituitary response to LHRH, LH pulsatility and plasma melatonin and prolactin changes in ewe lambs treated with melatonin implants to delay pubertyJ Reprod Fertil19867811371483531504

 PubMedGoogle Scholar

KennawayDJGilmoreTADunstanEAPinealectomy delays puberty in ewe lambsJ Reprod Fertil19857411191254040570

 PubMedGoogle Scholar

KennawayDJHughesPEvan WettereWHMelatonin implants do not alter estrogen feedback or advance puberty in giltsAnim Reprod Sci2015156132225618532

 PubMed Web of Science ®Google Scholar

KennawayDJLight, neurotransmitters and the suprachiasmatic nucleus control of pineal melatonin production in the ratNeurosignals199764–6247254

 Google Scholar

BuchananKLYellonSMDelayed puberty in the male Djungarian hamster: effect of short photoperiod or melatonin treatment on the GnRH neuronal systemNeuroendocrinology1991542961021766555

 PubMed Web of Science ®Google Scholar

LarkinJEJonesJZuckerITemperature dependence of gonadal regression in Syrian hamsters exposed to short day lengthsAm J Physiol Regul Integr Comp Physiol20022823R744R75211832395

 PubMed Web of Science ®Google Scholar

GoodmanRLJansenHTBillingsHJCoolenLMLehmanMNNeural systems mediating seasonal breeding in the eweJ Neuroendocrinol201022767468120456601

 PubMed Web of Science ®Google Scholar

SimonneauxVAncelCPoirelVJGauerFKisspeptins and RFRP-3 act in concert to synchronize rodent reproduction with seasonsFront Neurosci201372223550229

 PubMed Web of Science ®Google Scholar