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Corticosteroid-binding globulin (CBG) in fetal development

J R Challis1, E T Berdusco, T M Jeffray

  • 1MRC Group in Fetal and Neonatal Health and Development, Lawson Research Institute, St Joseph's Health Centre, London, Ontario, Canada.

The Journal of Steroid Biochemistry and Molecular Biology
|June 1, 1995
PubMed
Summary
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Fetal sheep show increased corticosteroid-binding globulin (CBG) before birth, which helps regulate cortisol levels. This CBG mechanism is crucial for the hormonal changes leading to parturition.

Area of Science:

  • Reproductive Endocrinology
  • Fetal Physiology

Background:

  • Plasma cortisol increases in fetal sheep prepartum, linked to higher corticosteroid-binding activity.
  • This activity is associated with increased corticosteroid-binding globulin (CBG) biosynthesis in the fetal liver.

Purpose of the Study:

  • To investigate the role of CBG in fetal sheep's hypothalamic-pituitary-adrenal (HPA) axis regulation.
  • To determine if glucocorticoids influence hepatic CBG gene expression in the fetus.

Main Methods:

  • Measured plasma cortisol and corticosteroid-binding activity in fetal sheep.
  • Assessed corticosteroid-binding globulin (CBG) gene expression in the fetal liver.
  • Examined CBG presence in fetal tissues and pituitary.
  • Evaluated CBG's effect on cortisol's negative feedback on fetal pituitary cells in culture.

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Main Results:

  • Prepartum increase in plasma cortisol correlated with enhanced corticosteroid-binding activity, suggesting increased CBG.
  • Hepatic CBG gene expression was found to be upregulated by fetal glucocorticoid exposure.
  • CBG mRNA was detected in the fetal pituitary, and immunoreactive CBG in other fetal tissues.
  • CBG diminished cortisol's negative feedback on basal and CRH-stimulated ACTH output from fetal pituitary cells.

Conclusions:

  • CBG in fetal sheep plasma modulates cortisol's negative feedback on the pituitary and potentially the hypothalamus.
  • This interaction is a key component of the late-gestation fetal HPA axis activation cascade.
  • The CBG-cortisol interaction contributes to the hormonal events initiating parturition in fetal sheep.