Endocrine Abstracts

Introduction: The human foetal adrenal gland (HFA) is a highly active endocrine organ, producing large amounts of DHEA and DHEAS. Our understanding of HFA development is limited, however, and species differences mean that animal models are only of partial use. Maternal cigarette smoking is known to increase the post-natal risk of health complications of the foetus, and the mechanisms involved may include effects on the HFA.

Aim: To examine normal HFA development during the second trimester and determine whether it is affected by maternal smoking.

Methods: HFAs were obtained from elective terminations (REC04/S0802/21) of second trimester foetuses between 11-21 weeks of gestation. Foetuses were grouped according to sex, gestational age and maternal smoking. Key enzymes in the HFA steroidogenic pathway were investigated using real-time PCR, Western blot and immunohistochemistry (IHC).

Results: Maternal smoking was associated with a significant (P=0.004) increase in the growth trajectory of the HFA and a progressive decrease in plasma ACTH concentration (P<0.001) in male foetuses (n=53). The most highly expressed transcript was CYP17A1. Maternal smoking was associated with increased variability of STAR (P=0.001), CYP17A1 (P=0.02) and CYP21A2 (P=0.04) transcript expression in a sex-dependent manner although protein levels (Western blot) were unaffected. Transcripts levels of CYP11B1, CYP11B2, SULT2A1, and HSD3B were unaffected by maternal smoking. IHC of STAR, CYP11A1, and CYP17A1 showed that enzyme expression was predominantly found in the foetal zone. HSD3B was expressed at low levels in the definitive zone.

Conclusions: The HFA dominates foetal steroid endocrinology and this study provides detailed developmental data for the critical second trimester period. We also found that maternal smoking during pregnancy can dysregulate adrenal growth and transcript levels although it remains to be determined whether post-natal health and adrenal function are significantly compromised.