Differential effects of estrogen on corticosteroid-binding globulin forms suggests reduced cleavage in pregnancy
Open accessAbstract
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).”
From Higher Circulating Cortisol in the Follicular vs. Luteal Phase of the Menstrual Cycle: A Meta-Analysis (2020) · cites this paper as [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
- ORCID
- Venue
- Journal of the Endocrine Society
- Publisher
- The Endocrine Society
- Published
- 2017-02-13
- Volume
- 1
- Issue
- 3
- Pages
- 202-210
- ISSN
- 2472-1972 (ISSN-L)
- PMC
- PMC5686768
- 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
- gold
- doi.org
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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