Delayed hepcidin response explains the lag period in iron absorption following a stimulus to increase erythropoiesis.
BACKGROUND
The delay of several days between an erythropoietic stimulus and the subsequent increase in intestinal iron absorption is commonly believed to represent the time required for body signals to programme the immature crypt enterocytes and for these cells to migrate to the villus. Recent data however suggest that signals from the body to alter absorption are mediated by circulating hepcidin and that this peptide exerts its effect on mature villus enterocytes.


METHODS
We have examined the delay in the absorptive response following stimulated erythropoiesis using phenylhydrazine induced haemolysis and correlated this with expression of hepcidin in the liver and iron transporters in the duodenum.


RESULTS
There was a delay of four days following haemolysis before a significant increase in iron absorption was observed. Hepatic hepcidin expression did not decrease until day 3, reaching almost undetectable levels by days 4 and 5. This coincided with the increase in duodenal expression of divalent metal transporter 1, duodenal cytochrome b, and Ireg1.


CONCLUSIONS
These results suggest that the delayed increase in iron absorption following stimulated erythropoiesis is attributable to a lag in the hepcidin response rather than crypt programming, and are consistent with a direct effect of the hepcidin pathway on mature villus enterocytes.
Frazer
D M
DM
Iron Metabolism Laboratory, Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Brisbane, Queensland 4029, Australia.
Inglis
H R
HR
Wilkins
S J
SJ
Millard
K N
KN
Steele
T M
TM
McLaren
G D
GD
McKie
A T
AT
Vulpe
C D
CD
Anderson
G J
GJ
D000704:Analysis of Variance; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism*; D004920:Erythropoiesis / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D006461:Hemolysis / Q000187:drug effects / Q000502:physiology; D064451:Hepcidins; D007408:Intestinal Absorption / Q000502:physiology*; D007501:Iron / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D010659:Phenylhydrazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014168:Transferrin / Q000378:metabolism
D023181:Antimicrobial Cationic Peptides; C578703:Hamp protein, rat; D064451:Hepcidins; D010659:Phenylhydrazines; D014168:Transferrin; C030299:phenylhydrazine; D007501:Iron