PMID- 31920956
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200113
IS  - 1664-2392 (Print)
IS  - 1664-2392 (Electronic)
IS  - 1664-2392 (Linking)
VI  - 10
DP  - 2019
TI  - Molecular and Environmental Mechanisms Regulating Puberty Initiation: An 
      Integrated Approach.
PG  - 828
LID - 10.3389/fendo.2019.00828 [doi]
LID - 828
AB  - The mechanisms underlying the initiation of puberty, one of the cornerstones of 
      human evolution, have not been fully elucidated as yet. However, recently, an 
      accumulating body of evidence has helped unravel several critical aspects of the 
      process. It is clear that a change in the pattern of pituitary gonadotropin 
      secretion serves as a hormonal trigger for puberty induction. This change is 
      directly guided by the hypothalamic GnRH pulse generation, a phenomenon regulated 
      by the Kisspeptin-Neurokinin-Dynorphin (KNDy) system also in the hypothalamus. 
      This represents the kisspeptin molecule, which is crucial in augmenting GnRH 
      secretion at puberty, whose secretion is fine-tuned by the opposing signals 
      neurokinin B and dynorphin. Recently, the novel kisspeptin inhibitory signal 
      MKRN3 was described, whose role in puberty initiation provided further insight 
      into the mechanistic aspects of pubertal onset. Furthermore, the description of 
      higher inhibitory and stimulatory signals acting upstream of the KNDy neurons 
      suggested that the trigger point of puberty is located upstream of the KNDy 
      system and the GnRH pulse generator. However, the mechanism of pubertal onset 
      should not be considered as an isolated closed loop system. On the contrary, it 
      is influenced by such factors as adipose tissue, gastrointestinal function, 
      adrenal androgen production, energy sensing, and physical and psychosocial 
      stress. Also, fetal and early life stressful events, as well as exposure to 
      endocrine disruptors, may play important roles in pubertal initiation, the latter 
      primarily through epigenetic modifications. Here we present the available data in 
      the field and attempt to provide an integrated view of this unique and crucial 
      phenomenon.
CI  - Copyright (c) 2019 Livadas and Chrousos.
FAU - Livadas, Sarantis
AU  - Livadas S
AD  - Endocrine Unit, Metropolitan Hospital, Athens, Greece.
FAU - Chrousos, George P
AU  - Chrousos GP
AD  - UNESCO Chair on Adolescent Health Care, University Research Institute of Maternal 
      and Child Health and Precision Medicine, Aghia Sophia Children's Hospital, 
      National and Kapodistrian University of Athens, Athens, Greece.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20191206
PL  - Switzerland
TA  - Front Endocrinol (Lausanne)
JT  - Frontiers in endocrinology
JID - 101555782
PMC - PMC6915095
OTO - NOTNLM
OT  - adrenarche
OT  - endocrine disruptor (ECD)
OT  - epigenetics
OT  - puberty
OT  - stress
EDAT- 2020/01/11 06:00
MHDA- 2020/01/11 06:01
PMCR- 2019/01/01
CRDT- 2020/01/11 06:00
PHST- 2019/07/24 00:00 [received]
PHST- 2019/11/13 00:00 [accepted]
PHST- 2020/01/11 06:00 [entrez]
PHST- 2020/01/11 06:00 [pubmed]
PHST- 2020/01/11 06:01 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - 10.3389/fendo.2019.00828 [doi]
PST - epublish
SO  - Front Endocrinol (Lausanne). 2019 Dec 6;10:828. doi: 10.3389/fendo.2019.00828. 
      eCollection 2019.