Altered Steroidome in Women with Gestational Diabetes Mellitus: Focus on Neuroactive and Immunomodulatory Steroids from the 24th Week of Pregnancy to Labor

Abstract

Gestational diabetes mellitus (GDM) is a complication in pregnancy, but studies focused on the steroidome in patients with GDM are not available in the public domain. This article evaluates the steroidome in GDM+ and GDM− women and its changes from 24 weeks (± of gestation) to labor. The study included GDM+ (n = 44) and GDM− women (n = 33), in weeks 24–28, 30–36 of gestation and at labor and mixed umbilical blood after delivery. Steroidomic data (101 steroids quantified by GC-MS/MS) support the concept that the increasing diabetogenic effects with the approaching term are associated with mounting progesterone levels. The GDM+ group showed lower levels of testosterone (due to reduced AKR1C3 activity), estradiol (due to a shift from the HSD17B1 towards HSD17B2 activity), 7-oxygenated androgens (competing with cortisone for HSD11B1 and shifting the balance from diabetogenic cortisol towards the inactive cortisone), reduced activities of SRD5As, and CYP17A1 in the hydroxylase but higher CYP17A1 activity in the lyase step. With the approaching term, the authors found rising activities of CYP3A7, AKR1C1, CYP17A1 in its hydroxylase step, but a decline in its lyase step, rising conjugation of neuroinhibitory and pregnancy-stabilizing steroids and weakening AKR1D1 activity.

Effect of maternal body mass index on the steroid profile in women with gestational diabetes mellitus

“…Our study confirmed elevated serum DHEA, T, and A4 levels in women with GDM. However, a latest study reveals that serum T and E2 levels is reduced with the increasing of gestational age, while DHEA, A4 and E1 were found to be unrelated to GDM ( 33 ). This finding goes against our work.…”

“…Aromatase knockout mice have decreased E2 levels, accompanied by reduced glucose oxidation, elevated adiposity, and insulin levels ( 44 , 45 ). E2 is an important antidiabetic steroid operating via binding to nuclear receptors as well as via modulation of ion channels controlling the secretion of pancreatic hormones ( 33 , 46 ). Therefore, E2 deficiency in GDM women with overweight may be an important component participating in the pathophysiology of GDM.…”