Localization and gestation-dependent pattern of corticotrophin-releasing factor receptor subtypes in ovine fetal distal colon.
Meconium passage is frequently observed in association with feto-maternal stress factors such as hypoxia and infection, but the triggering mechanism is unknown. We hypothesize that differential regulation of corticotrophin-releasing factor (CRF) receptors during gestation play an important role in determining the susceptibilities of the fetus to stress-induced in utero meconium passage at term. We examined the innervation patterns of CRF-receptor type 1 (CRF-R1), a stimulator of gastrointestinal motility and CRF-receptor type II (CRF-R2), an inhibitor of gastrointestinal motility in ovine fetal distal colonic segments from very preterm to term gestation. Both CRF-R1 and CRF-R2 receptors were present in muscularis mucosa as well as in longitudinal and circular smooth muscle layers in fetal distal colonic segments at all gestational ages. Quantitative image analysis indicated a 42% increase in CRF-R1 receptor immunoreactivity in muscularis mucosa and a 30% in longitudinal smooth muscle layers from very preterm to term. In contrast, CRF-R2 receptor immunoreactivity in muscularis mucosa as well as in longitudinal and circular smooth muscle layers decreased by 38%, 55% and 51%, respectively, at term. The percentage of enteric ganglia and the number of enteric neurons expressing CRF-R1 receptors were high at term. Western blot analysis identified 235 and 50 kDa molecular species of CRF-R1 receptors and 37 and 28 kDa molecular species of CRF-R2 receptors. In summary, we speculate that downregulation of CRF-R2 receptor abundance with concurrent increases in CRF-R1 receptor levels in myenteric-smooth muscle unit with advancing gestation sensitizes the colonic motility responses to stressors.
Lakshmanan
J
J
Department of Obstetrics and Gynecology, LABioMed at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
Magee
T R
TR
Richard
J D
JD
Liu
G L
GL
Salido
E
E
Sugano
S K
SK
Ferrini
M
M
Ross
M G
MG
D000818:Animals; D015153:Blotting, Western; D003106:Colon / Q000196:embryology* / Q000294:innervation* / Q000378:metabolism*; D005333:Fetus; D005455:Fluorescent Antibody Technique; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D009197:Myenteric Plexus / Q000378:metabolism; D018019:Receptors, Corticotropin-Releasing Hormone / Q000096:biosynthesis*; D012756:Sheep; D000099052:CRF Receptor, Type 1
C101531:CRF receptor type 2; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1