Session: SUN 72-87-HPA Axis
Poster Board SUN-80
Methods: Serum cortisol levels were measured at 16, 28 and 36 weeks gestation in n=173 class III obese (BMI 44.0±4.5kg/m2) and n=107 lean (BMI 22.8±1.6kg/m2) pregnant women. Serial corticosteroid binding globulin (CBG) and corticotrophin releasing hormone (CRH) concentrations were measured in a subset (n=39 lean, 26 obese). Free cortisol levels were calculated using Coolen’s equation. Salivary cortisol was measured in samples collected at bed-time, waking and 30 minutes after waking. 11b-hydroxysteroid dehydrogenase type 2 (11βHSD2), which inactivates cortisol, and glucocorticoid receptor (GR) mRNAs were measured in first trimester (n=34) and term (n=56) placental samples. DNA methylation of key regions controlling GR and 11βHSD2 expression was measured by pyrosequencing. Ethical approval and informed consent was obtained.
Results: Cortisol, CRH and CBG levels were lower throughout pregnancy in obese women (all p<0.05). Cortisol levels rose similarly during pregnancy in both obese and lean groups and the diurnal rhythm of cortisol was maintained. CBG levels also increased during pregnancy, although this change was lower in obese (1.21-fold (±0.32) vs 1.56-fold (±0.38), p<0.01). In obese, lower free cortisol at 16 weeks gestation was associated with higher birthweight after adjustment for confounders (r=-0.46, p<0.05). Placental expression of 11βHSD2 increased in association with increasing obesity in early pregnancy (r=0.46, p<0.01) and was highest in term placentas in obese women with macrosomic (>4000g) offspring (p<0.05). Placental expression of GR also increased in association with increasing obesity in early pregnancy (r=0.45, p<0.01), but was lowest in term placenta from obese women with macrosomic offspring (p<0.05). Methylation of the 1C promoter of GRwas lower in placentas of macrosomic offspring of obese women compared to lean (p<0.05).
Conclusions: The combination of lower CRH and CBG with associated lower circulating and bioavailable cortisol, together with a more effective placental barrier preventing maternal to fetal glucocorticoid transfer, may contribute to attenuated feto-placental glucocorticoid action and thus higher birthweight in the offspring of obese women.
Nothing to Disclose: JRO, SCR, HODC, MB, RS, JEN, BRW, JRS, AJD, RMR
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