PMID- 29072778
OWN - NLM
STAT- MEDLINE
DCOM- 20190814
LR  - 20191008
IS  - 1530-0277 (Electronic)
IS  - 0145-6008 (Print)
IS  - 0145-6008 (Linking)
VI  - 42
IP  - 1
DP  - 2018 Jan
TI  - Regulation of Kisspeptin Synthesis and Release in the Preoptic/Anterior 
      Hypothalamic Region of Prepubertal Female Rats: Actions of IGF-1 and Alcohol.
PG  - 61-68
LID - 10.1111/acer.13539 [doi]
AB  - BACKGROUND: Alcohol (ALC) causes suppressed secretion of prepubertal luteinizing 
      hormone-releasing hormone (LHRH). Insulin-like growth factor-1 (IGF-1) and 
      kisspeptin (Kp) are major regulators of LHRH and are critical for puberty. IGF-1 
      may be an upstream mediator of Kp in the preoptic area and rostral hypothalamic 
      area (POA/RHA) of the rat brain, a region containing both Kp and LHRH neurons. We 
      investigated the ability of IGF-1 to stimulate prepubertal Kp synthesis and 
      release in POA/RHA, and the potential inhibitory effects of ALC. METHODS: 
      Immature female rats were administered either ALC (3 g/kg) or water via gastric 
      gavage at 0730 hours. At 0900 hours, both groups were subdivided where half 
      received either saline or IGF-1 into the brain third ventricle. A second dose of 
      ALC (2 g/kg) or water was administered at 1130 hours. Rats were killed 6 hours 
      after injection and POA/RHA region collected. RESULTS: IGF-1 stimulated Kp, an 
      action blocked by ALC. Upstream to Kp, IGF-1 receptor (IGF-1R) activation, as 
      demonstrated by the increase in insulin receptor substrate 1, resulted in 
      activation of Akt, tuberous sclerosis 2, ras homologue enriched in brain, and 
      mammalian target of rapamycin (mTOR). ALC blocked the central action of IGF-1 to 
      induce their respective phosphorylation. IGF-1 specificity and ALC specificity 
      for the Akt-activated mTOR pathway were demonstrated by the absence of effects on 
      PRAS40. Furthermore, IGF-1 stimulated Kp release from POA/RHA incubated in vitro. 
      CONCLUSIONS: IGF-1 stimulates prepubertal Kp synthesis and release following 
      activation of a mTOR signaling pathway, and ALC blocks this pathway at the level 
      of IGF-1R.
CI  - Copyright (c) 2017 by the Research Society on Alcoholism.
FAU - Hiney, Jill K
AU  - Hiney JK
AUID- ORCID: 0000-0001-9286-9229
AD  - Department of Veterinary Integrative Biosciences, College of Veterinary Medicine, 
      Texas A&M University, College Station, Texas.
FAU - Srivastava, Vinod K
AU  - Srivastava VK
AD  - Department of Veterinary Integrative Biosciences, College of Veterinary Medicine, 
      Texas A&M University, College Station, Texas.
FAU - Vaden Anderson, Danielle N
AU  - Vaden Anderson DN
AD  - Department of Veterinary Integrative Biosciences, College of Veterinary Medicine, 
      Texas A&M University, College Station, Texas.
FAU - Hartzoge, Nicole L
AU  - Hartzoge NL
AD  - Department of Veterinary Integrative Biosciences, College of Veterinary Medicine, 
      Texas A&M University, College Station, Texas.
FAU - Dees, William L
AU  - Dees WL
AD  - Department of Veterinary Integrative Biosciences, College of Veterinary Medicine, 
      Texas A&M University, College Station, Texas.
LA  - eng
GR  - R01 AA007216/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20171204
PL  - England
TA  - Alcohol Clin Exp Res
JT  - Alcoholism, clinical and experimental research
JID - 7707242
RN  - 0 (Kiss1 protein, rat)
RN  - 0 (Kisspeptins)
RN  - 0 (insulin-like growth factor-1, rat)
RN  - 3K9958V90M (Ethanol)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
MH  - Animals
MH  - Ethanol/*administration & dosage
MH  - Female
MH  - Insulin-Like Growth Factor I/*administration & dosage
MH  - Kisspeptins/*biosynthesis
MH  - Pregnancy
MH  - Preoptic Area/*drug effects/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sexual Maturation/*drug effects/physiology
PMC - PMC5750128
MID - NIHMS915604
OTO - NOTNLM
OT  - *Alcohol
OT  - *IGF-1, mTOR
OT  - *Kisspeptin
OT  - *Puberty
COIS- Declaration of interest: The authors have no conflict of interest.
EDAT- 2017/10/27 06:00
MHDA- 2019/08/15 06:00
PMCR- 2019/01/01
CRDT- 2017/10/27 06:00
PHST- 2017/09/20 00:00 [received]
PHST- 2017/10/18 00:00 [accepted]
PHST- 2017/10/27 06:00 [pubmed]
PHST- 2019/08/15 06:00 [medline]
PHST- 2017/10/27 06:00 [entrez]
PHST- 2019/01/01 00:00 [pmc-release]
AID - 10.1111/acer.13539 [doi]
PST - ppublish
SO  - Alcohol Clin Exp Res. 2018 Jan;42(1):61-68. doi: 10.1111/acer.13539. Epub 2017 
      Dec 4.