Hormonal regulation of puberty onset in female rats: is leptin a missing link?

S. Zeinoaldini

Research output: Thesisinternal PhD, WU


Numerous factors in the hypothalamus-pituitary-gonadal axis (HPG) are involved in the timing of puberty onset.Leptin signals the nutritional status and the presence of an adequate amount of loaded adipose tissue, as a long-term resource of energy, to the brain which in response switches on the reproduction process (i.e. puberty onset).The growth hormone-insulin-like growth factor I (GH/IGF-I) axis is also thought to be involved in the timing of puberty onset. The aim of this thesis was to test the hypothesis that leptin may directly or indirectly via theGH/IGFI-I axistrigger the onset of puberty onset in female rats.

 First, we carried out a series of descriptive and basic studies.Time of puberty onset was monitored by scoring the moment of vaginal opening (VO).The data showed a strong positive correlation between body fat and leptin levels, and showed leptin is increasing over the prepubertal period. Then, we aimed to find out the effects of food-restriction (FR) on puberty onset, body fat, plasma leptin levels and body temperature. FR postponed time of VO. Body fat, plasma leptin levels and body temperature in the FR rats were significantly lower than the controls throughout the experiment.

 To find outif leptin is the signal initiating the onset of puberty, we used FR rats as a model for delayed puberty onset, and centrally (icv) or peripherally (sc) administered leptin, or we centrally (icv) immunoneutralized leptin. Central leptin infusion not only restored the delay in puberty onset caused by food restriction but also advanced sexual maturation in normally fed animals.Like central infusion, also peripheral leptin infusion restored puberty onset in FR animals. So, we showed an advancing effect of both centrally and peripherally infused leptin on puberty onset in prepubertal female rats.The central immunoneutralization of leptin on the other hand, postponed puberty onset. We therefore conclude that leptin is one of the crucial factors triggering puberty onset in female rats.

In the FR model system we then centrally (icv) infused GH.The infusion of GH postponed puberty onset in normally fed rats, but advanced puberty onset in FR animals. Also,the plasma leptin levels in the GH-infused animals were significantly higher than their controls and increased as GH infusion proceeded.Central infusion of GH antiserum (AS) advanced puberty onset in the pair-fed animals but not in the ad lib-fed animals. Also the central infusion of somatostatin worked likewise in both groups. These findings match with the results of the central infusion of GH which also advanced puberty onset in FR animals only.Finally, we centrally (icv) infused IGF-I in FR rats. Central infusion of IGF-I significantly postponed puberty onset in ad libitum fed animals.Immunoneutralization of endogenous IGF-I enhanced prevailing plasma leptin levels, but there was no effect on the timing of puberty onset. Centrally-present endogenous IGF-I does not appear to be involved in puberty onset although it seems to inhibit leptin secretion.In conclusion, our findings provide further evidence that leptin, a hormone produced mainly by adipose tissue, is an important and crucial signal between the bodily nutritional status and the brain (i.e. the hypothalamus) to trigger puberty onset. Furthermore, we suggest that there is a functional interaction between growth hormone (GH) and leptin to initiate puberty in female rats.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • Wageningen University
  • van der Heide, D., Promotor
  • van de Heijning, H.J.M., Co-promotor, External person
Award date3 Jun 2005
Place of PublicationWageningen
Print ISBNs9789085042013
Publication statusPublished - 3 Jun 2005


  • rats
  • female animals
  • polypeptides
  • hormones
  • puberty
  • hormonal control
  • adipose tissue
  • animal experiments
  • endocrinology


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