PMID- 21050473
OWN - NLM
STAT- MEDLINE
DCOM- 20110209
LR  - 20211020
IS  - 1477-7827 (Electronic)
IS  - 1477-7827 (Linking)
VI  - 8
DP  - 2010 Nov 4
TI  - Expression of genes related to the hypothalamic-pituitary-adrenal axis in murine 
      fetal lungs in late gestation.
PG  - 134
LID - 10.1186/1477-7827-8-134 [doi]
AB  - BACKGROUND: Lung maturation is modulated by several factors, including 
      glucocorticoids. Expression of hypothalamic-pituitary-adrenal (HPA) axis-related 
      components, with proposed or described local regulatory systems analogous to the 
      HPA axis, was reported in peripheral tissues. Here, HPA axis-related genes were 
      studied in the mouse developing lung during a period overlapping the surge of 
      surfactant production. METHODS: Expression of genes encoding for 
      corticotropin-releasing hormone (CRH), CRH receptors (CRHR) 1 and 2beta, 
      CRH-binding protein, proopiomelanocortin (POMC), melanocortin receptor 2 (MC2R), 
      and glucocorticoid receptor was quantified by real-time PCR and localized by in 
      situ hydridization in fetal lungs at gestational days (GD) 15.5, 16.5, and 17.5, 
      and was also quantified in primary mesenchymal- and epithelial cell-enriched 
      cultures. In addition, the capability of CRH and adrenocorticotropic hormone 
      (ACTH) to stimulate pulmonary expression of enzymes involved in the adrenal 
      pathway of glucocorticoid synthesis was addressed, as well as the glucocorticoid 
      production by fetal lung explants. RESULTS: We report that all the studied genes 
      are expressed in fetal lungs according to different patterns. On GD 15.5, Mc2r 
      showed peaks in expression in samples that have previously presented high mRNA 
      levels for glucocorticoid synthesizing enzymes, including 11beta-hydroxylase 
      (Cyp11b1). Crhr1 mRNA co-localized with Pomc mRNA in cells surrounding the 
      proximal epithelium on GD 15.5 and 16.5. A transition in expression sites toward 
      distal epithelial cells was observed between GD 15.5 and 17.5 for all the studied 
      genes. CRH or ACTH stimulation of genes involved in the adrenal pathway of 
      glucocorticoid synthesis was not observed in lung explants on GD 15.5, whereas 
      CRH significantly increased expression of 21-hydroxylase (Cyp21a1) on GD 17.5. A 
      deoxycorticosterone production by fetal lung explants was observed. CONCLUSIONS: 
      Temporal and spatial modulations of expression of HPA axis-related genes in late 
      gestation are consistent with roles for these genes in lung development. Our data 
      are likely to lead to valuable insights in relation to lung diseases originating 
      from lung immaturity.
FAU - Simard, Marc
AU  - Simard M
AD  - Reproduction, Perinatal Health, and Child Health, CHUQ Research Center, Quebec 
      City, Quebec, Canada.
FAU - Cote, Melissa
AU  - Cote M
FAU - Provost, Pierre R
AU  - Provost PR
FAU - Tremblay, Yves
AU  - Tremblay Y
LA  - eng
GR  - IC87816/Canadian Institutes of Health Research/Canada
GR  - IC90831/Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101104
PL  - England
TA  - Reprod Biol Endocrinol
JT  - Reproductive biology and endocrinology : RB&E
JID - 101153627
RN  - 0 (Glucocorticoids)
RN  - 0 (Receptors, Glucocorticoid)
RN  - 9002-60-2 (Adrenocorticotropic Hormone)
RN  - 9015-71-8 (Corticotropin-Releasing Hormone)
SB  - IM
MH  - Adrenocorticotropic Hormone/pharmacology
MH  - Animals
MH  - Cells, Cultured
MH  - Corticotropin-Releasing Hormone/pharmacology
MH  - Female
MH  - Fetus/drug effects/embryology/metabolism
MH  - *Gene Expression Regulation, Developmental/drug effects
MH  - Gestational Age
MH  - Glucocorticoids/genetics/metabolism
MH  - Hypothalamo-Hypophyseal System/drug effects/embryology/*metabolism
MH  - Lung/drug effects/*embryology/*metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Pituitary-Adrenal System/drug effects/embryology/*metabolism
MH  - Pregnancy
MH  - Receptors, Glucocorticoid/genetics/metabolism
PMC - PMC2989976
EDAT- 2010/11/06 06:00
MHDA- 2011/02/10 06:00
PMCR- 2010/11/04
CRDT- 2010/11/06 06:00
PHST- 2010/07/06 00:00 [received]
PHST- 2010/11/04 00:00 [accepted]
PHST- 2010/11/06 06:00 [entrez]
PHST- 2010/11/06 06:00 [pubmed]
PHST- 2011/02/10 06:00 [medline]
PHST- 2010/11/04 00:00 [pmc-release]
AID - 1477-7827-8-134 [pii]
AID - 10.1186/1477-7827-8-134 [doi]
PST - epublish
SO  - Reprod Biol Endocrinol. 2010 Nov 4;8:134. doi: 10.1186/1477-7827-8-134.