Cited by 33Adrenal Hormones and DisordersEstrogen and related hormone effectsStress Responses and Cortisol

Differential effects of estrogen on corticosteroid-binding globulin forms suggests reduced cleavage in pregnancy

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Marni Anne Nenke, Anna Zeng, Emily Jane Meyer, John G. Lewis, Wayne A. Rankin, Julie K. Johnston, Svjetlana Kireta, Shilpanjali Jesudason +1 more·2017·Journal of the Endocrine Society

Abstract

Corticosteroid-binding globulin (CBG) is secreted as high-affinity CBG (haCBG), which may be cleaved by tissue proteases to low-affinity CBG (laCBG), releasing free cortisol. Pregnancy and the estrogen-based combined oral contraceptive pill (COCP) increase CBG concentrations twofold to threefold. The relative effects of these two hyperestrogenic states on the CBG affinity forms are unknown. We performed an observational study in 30 pregnant women, 27 COCP takers and 23 controls. We analyzed circulating total CBG, haCBG, laCBG, and free and total cortisol concentrations. In pregnancy, total CBG and haCBG were increased compared to controls (both P < 0.0001); however, laCBG concentrations were similar. In COCP takers, total CBG and haCBG were increased [802 ± 41 vs compared to controls (both P < 0.0001)], but laCBG was also increased (P = 0.03). Pregnancy and use of COCP were associated with a comparable rise in haCBG, but laCBG was lower in pregnancy (P < 0.0001). These results were consistent with an estrogen-mediated increase in CBG synthesis in both hyperestrogenemic states but with reduced CBG cleavage in pregnancy relative to the COCP, perhaps due to pregnancy-induced CBG glycosylation. Speculatively, increased circulating haCBG concentrations in pregnancy may provide an increased reservoir of CBG-bound cortisol to prepare for the risk of puerperal infection or allow for cortisol binding in the face of competition from increased circulating progesterone concentrations.

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  • Total CBG concentration reaches ~1,000 nmol/L in pregnancy and during the active phase of pill cycle containing ethinyl estradiol, substantially higher than the ~500 nmol/L in non-pregnant, non-OC taking individuals.

    “Nenke et al. (90) report that total CBG concentration reaches ~1,000 nmol/L in pregnancy as well as during the active phase of pill cycle containing ethinyl estradiol. These expression levels are substantially higher than the CBG levels of ~500 nmol/L determined in non-pregnant, non-OC taking individuals (90).”

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Authors
Nenke, M. A., Zeng, A., Meyer, E. J., Lewis, J. G., Rankin, W. A., Johnston, J. K., Kireta, S., Jesudason, S., & Torpy, D. J.
Affiliations
  • Royal Adelaide Hospital (AU)
  • Canterbury Health Laboratories (NZ)
  • South Australia Pathology (AU)
  • The University of Adelaide (AU)
Corresponding author
Marni Anne Nenke
Venue
Journal of the Endocrine Society
Published
2017-02-13
Volume
1
Issue
3
Pages
202-210
ISSN
2472-1972 (ISSN-L)
OpenAlex
W2799575820
Cited by
33
References
54
Citations by year
2026: 2 · 2025: 2 · 2024: 5 · 2023: 2 · 2022: 1 · 2021: 5 · 2020: 7 · 2019: 4 · 2018: 3 · 2017: 2
FWCI
3.46
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Journal of the Endocrine Society (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords
corticosteroid-binding globulin, estrogen, pregnancy, combined oral contraceptives, free cortisol, hyperestrogenism, postpartum infection, progesterone

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