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

Marni A. Nenke, Anna Zeng, Emily J. Meyer, John G. Lewis, Wayne Rankin, Julie Johnston, Svjetlana Kireta, Shilpanjali Jesudason, David J. Torpy

Research output: Contribution to journalArticle


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 estrogenbased 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 CBGand 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.

Original languageEnglish
Pages (from-to)202-210
Number of pages9
JournalJournal of the Endocrine Society
Issue number3
Publication statusPublished - 1 Jan 2017


  • Cortisol
  • Estrogen
  • High-affinity CBG
  • Low-affinity CBG
  • Oral contraceptive pill
  • Pregnancy

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

Cite this