Role of Hypothalamic-Pituitary Axis in EGF Action on Maturation of Adrenal Gland in Fetal Rhesus Monkey In Vivo

Jul 31, 2001Pediatric research

How the hormone control system affects growth factor action on adrenal gland development in fetal rhesus monkeys

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Abstract

EGF administered intraperitoneally (40 microg) significantly increased the width of the definitive zone in fetal rhesus monkeys compared to controls.

Definitive zone width and cortical width of 3betaHSD staining were significantly greater in EGF IP-treated fetuses than in controls and those treated with EGF+BLOCK.
EGF IP administration increased 3betaHSD expression in the definitive zone and induced it extensively in the transitional zone of the adrenal cortex.
Cytochrome P-450 11beta-hydroxylase/aldosynthase showed detectable levels in the definitive zone following EGF IP treatment.
The combination treatment of EGF+BLOCK inhibited 3betaHSD expression in the transitional zone but did not prevent its increase in the definitive zone.
EGF administered intraamniotically did not significantly affect the definitive zone or cortical width of 3betaHSD staining compared to controls.

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We determined the route of action of epidermal growth factor (EGF) [intraperitoneal (IP) versus intraamniotic administration] on adrenal development and whether its effects are mediated via the fetal hypothalamic-pituitary axis in the fetal rhesus monkey in vivo. EGF (40 microg) was administered IP (n = 9) or intraamniotic (n = 6) at 121, 123, 125, and 127 d gestation (term, approximately 165 +/- 10 d gestation). In addition, a competitive corticotropin-releasing factor antagonist ([D-phenylalanine(12), Norleucine(21,38)] corticotropin-releasing factor(12-41) to block fetal pituitary ACTH secretion; 400 microg IP) and metyrapone (11beta-hydroxylase inhibitor to block adrenal cortisol synthesis; 15 mg IP and 15 mg intraamniotic) were administered, in combination with EGF (EGF+BLOCK; 40 microg IP; n = 4 fetuses). Control fetuses (n = 6) received saline injections in an equivalent volume. On gestational d 128, a hysterotomy was performed, and fetal adrenals were collected for morphometric analyses and immunocytochemical localization of 3beta -hydroxysteroid dehydrogenase (3betaHSD) and cytochrome P-450 11beta -hydroxylase/aldosynthase. Definitive zone (DZ) width and cortical width of 3betaHSD staining were significantly greater (p < 0.05) in the EGF IP-treated fetuses compared with controls and EGF+BLOCK. With EGF IP, 3betaHSD was increased in the DZ and induced extensively in the transitional zone of the fetal adrenal cortex, and cytochrome P-450 11beta-hydroxylase/aldosynthase immunoreactivity was induced to detectable levels in the DZ. The administration of EGF+BLOCK inhibited the expression of 3betaHSD in the transitional zone, but 3betaHSD expression was still increased in the DZ and cytochrome P-450 11beta-hydroxylase/aldosynthase immunoreactivity was induced in the DZ. EGF intraamniotic administration had no significant effect on the width of the DZ or cortical width of 3betaHSD staining compared with controls. These data suggest that EGF acts via the hypothalamic-pituitary axis to modulate adrenal cortical growth and functional maturation of the transitional zone (the putative zona fasciculata), whereas EGF can act independently of the hypothalamic-pituitary axis to stimulate functional maturation of the DZ (the putative zona glomerulosa).

Role of Hypothalamic-Pituitary Axis in EGF Action on Maturation of Adrenal Gland in Fetal Rhesus Monkey In Vivo

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