PMID- 26566264
OWN - NLM
STAT- MEDLINE
DCOM- 20160801
LR  - 20190111
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Print)
IS  - 0021-9541 (Linking)
VI  - 231
IP  - 7
DP  - 2016 Jul
TI  - Sex Steroids Influence Brain-Derived Neurotropic Factor Secretion From Human 
      Airway Smooth Muscle Cells.
PG  - 1586-92
LID - 10.1002/jcp.25254 [doi]
AB  - Brain derived neurotropic factor (BDNF) is emerging as an important player in 
      airway inflammation, remodeling, and hyperreactivity. Separately, there is 
      increasing evidence that sex hormones contribute to pathophysiology in the lung. 
      BDNF and sex steroid signaling are thought to be intricately linked in the brain. 
      There is currently little information on BDNF and sex steroid interactions in the 
      airway but is relevant to understanding growth factor signaling in the context of 
      asthma in men versus women. In this study, we assessed the effect of sex steroids 
      on BDNF expression and secretion in human airway smooth muscle (ASM). Human ASM 
      was treated with estrogen (E2 ) or testosterone (T, 10 nM each) and intracellular 
      BDNF and secreted BDNF measured. E2 and T significantly reduced secretion of 
      BDNF; effects prevented by estrogen and androgen receptor inhibitor, ICI 182,780 
      (1 muM), and flutamide (10 muM), respectively. Interestingly, no significant 
      changes were observed in intracellular BDNF mRNA or protein expression. High 
      affinity BDNF receptor, TrkB, was not altered by E2 or T. E2 (but not T) 
      significantly increased intracellular cyclic AMP levels. Notably, Epac1 and Epac2 
      expression were significantly reduced by E2 and T. Furthermore, SNARE complex 
      protein SNAP25 was decreased. Overall, these novel data suggest that 
      physiologically relevant concentrations of E2 or T inhibit BDNF secretion in 
      human ASM, suggesting a potential interaction of sex steroids with BDNF in the 
      airway that is different from brain. The relevance of sex steroid-BDNF 
      interactions may lie in their overall contribution to airway diseases such as 
      asthma.
CI  - (c) 2015 Wiley Periodicals, Inc.
FAU - Wang, Sheng-Yu
AU  - Wang SY
AD  - Department of Respiratory Medicine, First Affiliated Hospital of Xi'an Medical 
      University, Xi'an, Shaanxi, PR China.
AD  - Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota.
FAU - Freeman, Michelle R
AU  - Freeman MR
AD  - Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota.
FAU - Sathish, Venkatachalem
AU  - Sathish V
AD  - Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota.
AD  - Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, 
      Minnesota.
FAU - Thompson, Michael A
AU  - Thompson MA
AD  - Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota.
FAU - Pabelick, Christina M
AU  - Pabelick CM
AD  - Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota.
AD  - Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, 
      Minnesota.
FAU - Prakash, Y S
AU  - Prakash YS
AD  - Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota.
AD  - Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, 
      Minnesota.
LA  - eng
GR  - R01 HL056470/HL/NHLBI NIH HHS/United States
GR  - R01 HL088029/HL/NHLBI NIH HHS/United States
GR  - R01 HL123494/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20151126
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Estrogens)
RN  - 0 (Gonadal Steroid Hormones)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Receptors, Androgen)
RN  - 22X328QOC4 (Fulvestrant)
RN  - 3XMK78S47O (Testosterone)
RN  - 4TI98Z838E (Estradiol)
RN  - 76W6J0943E (Flutamide)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.10.1 (tropomyosin-related kinase-B, human)
SB  - IM
MH  - Airway Remodeling/*genetics
MH  - Asthma/*genetics/metabolism/pathology
MH  - Brain-Derived Neurotrophic Factor/*biosynthesis/genetics/metabolism
MH  - Estradiol/administration & dosage/analogs & derivatives
MH  - Estrogens/administration & dosage
MH  - Female
MH  - Flutamide/administration & dosage
MH  - Fulvestrant
MH  - Gene Expression Regulation/drug effects
MH  - Gonadal Steroid Hormones/*administration & dosage
MH  - Humans
MH  - Inflammation/*genetics/pathology
MH  - Male
MH  - Membrane Glycoproteins/biosynthesis
MH  - Myocytes, Smooth Muscle/metabolism/pathology
MH  - Protein-Tyrosine Kinases/biosynthesis
MH  - Receptor, trkB
MH  - Receptors, Androgen/drug effects
MH  - Testosterone/administration & dosage
PMC - PMC4890164
MID - NIHMS789512
EDAT- 2015/11/14 06:00
MHDA- 2016/08/02 06:00
PMCR- 2017/07/01
CRDT- 2015/11/14 06:00
PHST- 2015/11/10 00:00 [received]
PHST- 2015/11/11 00:00 [accepted]
PHST- 2015/11/14 06:00 [entrez]
PHST- 2015/11/14 06:00 [pubmed]
PHST- 2016/08/02 06:00 [medline]
PHST- 2017/07/01 00:00 [pmc-release]
AID - 10.1002/jcp.25254 [doi]
PST - ppublish
SO  - J Cell Physiol. 2016 Jul;231(7):1586-92. doi: 10.1002/jcp.25254. Epub 2015 Nov 
      26.