PMID- 22434086
OWN - NLM
STAT- MEDLINE
DCOM- 20120629
LR  - 20211021
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 153
IP  - 5
DP  - 2012 May
TI  - The ERbeta ligand 5alpha-androstane, 3beta,17beta-diol (3beta-diol) regulates hypothalamic 
      oxytocin (Oxt) gene expression.
PG  - 2353-61
LID - 10.1210/en.2011-1002 [doi]
AB  - The endocrine component of the stress response is regulated by glucocorticoids 
      and sex steroids. Testosterone down-regulates hypothalamic-pituitary-adrenal 
      (HPA) axis activity; however, the mechanisms by which it does so are poorly 
      understood. A candidate testosterone target is the oxytocin gene (Oxt), given 
      that it too inhibits HPA activity. Within the paraventricular nucleus of the 
      hypothalamus, oxytocinergic neurons involved in regulating the stress response do 
      not express androgen receptors but do express estrogen receptor-beta (ERbeta), which 
      binds the dihydrotestosterone metabolite 3beta,17beta-diol (3beta-diol). Testosterone 
      regulation of the HPA axis thus appears to involve the conversion to the 
      ERbeta-selective ligand 5alpha-androstane, 3beta-diol. To study mechanisms by which 3beta-diol 
      could regulate Oxt expression, we used a hypothalamic neuronal cell line derived 
      from embryonic mice that expresses Oxt constitutively and compared 3beta-diol with 
      estradiol (E2) effects. E2 and 3beta-diol elicited a phasic response in Oxt mRNA 
      levels. In the presence of either ligand, Oxt mRNA levels were increased for at 
      least 60 min and returned to baseline by 2 h. ERbeta occupancy preceded an increase 
      in Oxt mRNA levels in the presence of 3beta-diol but not E2. In tandem with ERbeta 
      occupancy, 3beta-diol increased occupancy of the Oxt promoter by cAMP response 
      element-binding protein and steroid receptor coactivator-1 at 30 min. At the same 
      time, 3beta-diol led to the increased acetylation of histone H4 but not H3. Taken 
      together, the data suggest that in the presence of 3beta-diol, ERbeta associates with 
      cAMP response element-binding protein and steroid receptor coactivator-1 to form 
      a functional complex that drives Oxt gene expression.
FAU - Sharma, Dharmendra
AU  - Sharma D
AD  - Department of Pharmacology and Neuroscience and Institute for Aging and 
      Alzheimer's Disease Research, University of North Texas Health Science Center, 
      Fort Worth, Texas 76107, USA.
FAU - Handa, Robert J
AU  - Handa RJ
FAU - Uht, Rosalie M
AU  - Uht RM
LA  - eng
GR  - R01 MH082900/MH/NIMH NIH HHS/United States
GR  - R01 NS039951/NS/NINDS NIH HHS/United States
GR  - R01-MH082900/MH/NIMH NIH HHS/United States
GR  - R01-NS039951/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20120320
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 25126-76-5 (Androstane-3,17-diol)
RN  - 4TI98Z838E (Estradiol)
RN  - 50-56-6 (Oxytocin)
SB  - IM
MH  - Androstane-3,17-diol/metabolism/*pharmacology
MH  - Animals
MH  - Cell Line
MH  - Cells, Cultured
MH  - Estradiol/metabolism/pharmacology
MH  - Gene Expression/drug effects
MH  - Hypothalamus/*drug effects/metabolism
MH  - Mice
MH  - Neurons/*drug effects/metabolism
MH  - Oxytocin/*genetics/metabolism
MH  - Promoter Regions, Genetic/drug effects
PMC - PMC3339641
EDAT- 2012/03/22 06:00
MHDA- 2012/06/30 06:00
PMCR- 2013/05/01
CRDT- 2012/03/22 06:00
PHST- 2012/03/22 06:00 [entrez]
PHST- 2012/03/22 06:00 [pubmed]
PHST- 2012/06/30 06:00 [medline]
PHST- 2013/05/01 00:00 [pmc-release]
AID - en.2011-1002 [pii]
AID - EN-11-1002 [pii]
AID - 10.1210/en.2011-1002 [doi]
PST - ppublish
SO  - Endocrinology. 2012 May;153(5):2353-61. doi: 10.1210/en.2011-1002. Epub 2012 Mar 
      20.