PMID- 17928160
OWN - NLM
STAT- MEDLINE
DCOM- 20080311
LR  - 20191210
IS  - 0306-4530 (Print)
IS  - 0306-4530 (Linking)
VI  - 32
IP  - 8-10
DP  - 2007 Sep-Nov
TI  - Neuroactive steroids modulate HPA axis activity and cerebral brain-derived 
      neurotrophic factor (BDNF) protein levels in adult male rats.
PG  - 1062-78
AB  - Depression is characterized by hypothalamo-pituitary-adrenocortical (HPA) axis 
      hyperactivity. In this major mood disorder, neurosteroids and neurotrophins, 
      particularly brain-derived neurotrophic factor (BDNF), seem to be implicated and 
      have some antidepressant effects. BDNF is highly involved in regulation of the 
      HPA axis, whereas neurosteroids effects have never been clearly established. In 
      this systematic in vivo study, we showed that the principal neuroactive steroids, 
      namely dehydroepiandrosterone (DHEA), pregnenolone (PREG) and their sulfate 
      esters (DHEA-S and PREG-S), along with allopregnanolone (ALLO), stimulated HPA 
      axis activity, while also modulating central BDNF contents. In detail, DHEA, 
      DHEA-S, PREG, PREG-S and ALLO induced corticotropin-releasing hormone (CRH) 
      and/or arginine vasopressin (AVP) synthesis and release at the hypothalamic 
      level, thus enhancing plasma adrenocorticotropin hormone (ACTH) and 
      corticosterone (CORT) concentrations. This stimulation of the HPA axis occurred 
      concomitantly with BDNF modifications at the hippocampus, amygdala and 
      hypothalamus levels. We showed that these neurosteroids induced rapid effects, 
      probably via neurotransmitter receptors and delayed effects perhaps after 
      metabolization in other neuroactive steroids. We highlighted that they had 
      peripheral effects directly at the adrenal level by inducing CORT release, 
      certainly after estrogenic metabolization. In addition, we showed that, at the 
      dose used, only DHEA, DHEA-S and PREG-S had antidepressant effects. In 
      conclusion, these results highly suggest that part of the HPA axis and 
      antidepressant effects of neuroactive steroids could be mediated by BDNF, 
      particularly at the amygdala level. They also suggest that neurosteroids effects 
      on central BDNF could partially explain the trophic properties of these 
      molecules.
FAU - Naert, Gaelle
AU  - Naert G
AD  - Universite Montpellier 2, F-34095 Montpellier, France.
FAU - Maurice, Tangui
AU  - Maurice T
FAU - Tapia-Arancibia, Lucia
AU  - Tapia-Arancibia L
FAU - Givalois, Laurent
AU  - Givalois L
LA  - eng
PT  - Evaluation Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071024
PL  - England
TA  - Psychoneuroendocrinology
JT  - Psychoneuroendocrinology
JID - 7612148
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Central Nervous System Depressants)
RN  - 0 (Neuropeptides)
RN  - 0 (Steroids)
RN  - 04Y4D91RG0 (pregnenolone sulfate)
RN  - 459AG36T1B (Dehydroepiandrosterone)
RN  - 57B09Q7FJR (Dehydroepiandrosterone Sulfate)
RN  - 73R90F7MQ8 (Pregnenolone)
RN  - BXO86P3XXW (Pregnanolone)
SB  - IM
MH  - Animals
MH  - Brain/*drug effects/metabolism
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Central Nervous System Depressants/pharmacology
MH  - Dehydroepiandrosterone/administration & dosage
MH  - Dehydroepiandrosterone Sulfate/administration & dosage
MH  - Hypothalamo-Hypophyseal System/*drug effects
MH  - Injections, Intraperitoneal
MH  - Male
MH  - Neuropeptides/administration & dosage/*pharmacology
MH  - Pituitary-Adrenal System/*drug effects
MH  - Pregnanolone/administration & dosage
MH  - Pregnenolone/administration & dosage
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Steroids/administration & dosage/*pharmacology
EDAT- 2007/10/12 09:00
MHDA- 2008/03/12 09:00
CRDT- 2007/10/12 09:00
PHST- 2007/03/28 00:00 [received]
PHST- 2007/09/04 00:00 [revised]
PHST- 2007/09/04 00:00 [accepted]
PHST- 2007/10/12 09:00 [pubmed]
PHST- 2008/03/12 09:00 [medline]
PHST- 2007/10/12 09:00 [entrez]
AID - S0306-4530(07)00209-0 [pii]
AID - 10.1016/j.psyneuen.2007.09.002 [doi]
PST - ppublish
SO  - Psychoneuroendocrinology. 2007 Sep-Nov;32(8-10):1062-78. doi: 
      10.1016/j.psyneuen.2007.09.002. Epub 2007 Oct 24.