Insulin-like Growth Factor 1 Mediates Adrenal Development Dysfunction in Offspring Rats Induced by Prenatal Food Restriction.

Abstract

BACKGROUND:

Our previous study demonstrated that prenatal food restriction (PFR) could induce the dysfunction of the hypothalamic-pituitary-adrenal axis and glucocorticoid-related glucose and lipid metabolic alterations in adult offspring rats.

AIM OF THE STUDY:

To investigate the intrauterine programming mechanism of adrenal dysfunction in the PFR offspring rats.

METHODS:

From gestational days (GDs) 11-20, pregnant Wistar rats were fed a restricted diet (50% of the daily food intake of control rats, 60 g/kg·d). Some were executed at GD20, while the others survived to full-term delivery; all pups were fed a high-fat diet (HFD) after weaning. The serum corticosterone concentration, expression level of adrenal steroidal synthetase, and insulin-like growth factor 1 (IGF1) signaling pathway were tested.

RESULTS:

We confirmed that the fetal body weight of the PFR group was lower than that of the control group, and the mRNA expression of adrenal steroidogenic acute regulatory protein, cytochrome P450 cholesterol side chain cleavage, 3β-hydroxysteroid dehydrogenase, and steroid 11β-hydroxylase (P450c11) were decreased in the PFR fetal rats. The maternal and fetal serum corticosterone levels were significantly increased in the PFR groups. Furthermore, the expression of the adrenal IGF1 signaling pathway (including IGF1, IGF1R, and Akt1) was suppressed. However, after a post-weaning HFD, the body weight gain rates and serum corticosterone levels were elevated, and the expression of adrenal steroid 21-hydroxylase and P450c11, as well as the IGF1 signaling pathway, were significantly increased in the PFR group.

CONCLUSIONS:

These results showed that a higher level of circulation corticosterone by PFR in utero inhibited adrenal IGF1 signaling and steroidogenesis, whereas post-weaning HFD induced adrenal steroidogenesis by an enhanced IGF1 signaling.

• Authors: Zheng He, Feng Lv, Yufeng Ding, Chunyan Zhu, Hegui Huang, Li Zhang, Yu Guo, Hui Wang
• Journal: Archives of medical research (Arch Med Res) Vol. 48 Issue 6 Pg. 488-497 (08 2017) ISSN: 1873-5487 [Electronic] United States
• PMID: 29203053 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 IMSS. Published by Elsevier Inc. All rights reserved.

Chemical References

• Phosphoproteins
• steroidogenic acute regulatory protein
• Insulin-Like Growth Factor I
• Cholesterol
• Glucose
• Corticosterone

Topics

• Adrenal Gland Diseases (metabolism)
• Animals
• Body Weight (physiology)
• Cholesterol (metabolism)
• Corticosterone (blood)
• Diet, Reducing (adverse effects)
• Disease Models, Animal
• Female
• Glucose (metabolism)
• Hypothalamo-Hypophyseal System (physiology)
• Insulin-Like Growth Factor I (metabolism, physiology)
• Phosphoproteins (metabolism)
• Pituitary-Adrenal System (physiology)
• Pregnancy
• Prenatal Exposure Delayed Effects (metabolism)
• Rats
• Rats, Wistar