AJP - Endocrinology and Metabolism, Vol 265, Issue 4 E667-E672, Copyright © 1993 by American Physiological Society
Content, in vivo release, and bioactivity of fetal pulmonary immunoreactive adrenocorticotropin
T. A. Cudd, M. I. Castro and C. E. Wood
Department of Physiology, University of Florida, Gainesville 32610.
We hypothesized that fetal lung contains and releases immunoreactive (ir)
adrenocorticotropin (ACTH). Fetal sheep lung (89-145 days gestation, n =
13) irACTH content was 4,100 +/- 672 (SE) pg/g lung wet wt compared with
5,425 +/- 1,403 (SE) pg/g in adults (n = 5) when measured by
radioimmunoassay (RIA). irACTH values normalized to protein content were
158 +/- 18 and 95 +/- 22 (SE) ng/g protein for fetuses and adults,
respectively. Grouped by age, < 90 days (n = 4), 131-139 days (n = 5),
and 143-145 days (n = 4), the values for irACTH were 184 +/- 28, 173 +/-
33, and 114 +/- 33 (SE) ng/g protein, respectively, and declined
significantly from < 90 days to adulthood. RIA serial dilution curve
slopes were different from standard in 7 of 13 fetuses and in all adults,
suggesting that irACTH structure differs from ACTH-(1-39). Acute in vivo
fetal pulmonary artery and vein sampling (n = 5, 120-128 days gestation)
revealed a mean difference of -609 +/- 476 (SE) pg/ml, a statistically
significant release of irACTH across the lung. Western blotting revealed
that pulmonary irACTH migrates in multiple immunostaining bands between
molecular weight 14,000 and 46,000 and does not colocalize with
ACTH-(1-39). Adrenal cell bioassay revealed that pulmonary irACTH is not
corticotropic. We concluded that ovine fetal lung contains
large-molecular-weight irACTH, that content declines from 90 days gestation
to adulthood, and that, under acute conditions, the fetal lung releases
irACTH substances in sufficient quantity to contribute to circulating
hormone concentrations of irACTH.
