ISSN 1662-4009 (online)

ESPE Yearbook of Paediatric Endocrinology (2019) 16 2.16 | DOI: 10.1530/ey.16.2.16


J Clin Endocrinol Metab. 2018 Dec 21. [Epub ahead of print]. doi: 10.1210/jc.2018-01759.

This study aimed to investigate Human fetal adrenal (HFA) steroidogenesis by analyzing adrenal glands from 1st and 2nd trimester. Steroidogenesis in the HFA is tightly regulated throughout the first and second trimesters, which is crucial because the adrenal steroid hormones affect the overall intrauterine endocrine environment from early fetal development. Elevated levels of HFA androgens can be a consequence of dysregulated adrenal steroid pathways (for example in congenital adrenal hyperplasia). HFA steroidogenesis is not well characterized during fetal development, as previous studies investigating the steroidogenic function have focused on either the first or the second/third trimester only, characterizing selected adrenal steroidogenic enzymes.

This study therefore aimed to collect detailed expression data of all the classic steroidogenic enzymes and determine the intra-adrenal steroid levels from the first- and second-trimester HFAs in one inclusive study. This study provides detailed characterizations of both male and female adrenal endocrine functions during the first and second trimesters of human fetal development. It is evident from the gene and protein expression patterns of steroidogenic enzymes, as well as the steroid measurements in tissues, that the HFA functions as an active steroidogenic organ from early development by producing high levels of mineralocorticoids, glucocorticoids, and androgens. Even from 8 weeks of gestation, a distinct expression pattern for the investigated adrenal steroidogenic enzymes was noted, with a major increase in gene expression in second-trimester samples for the majority of steroidogenic enzymes, with the exception of the unaltered expression of 3β-HSD2 and ARK1C3. On the basis of the intra-adrenal steroid hormone concentrations, the study found that androstenedione was the most abundant adrenal androgen synthesized via the classic steroidogenic pathway throughout the first and second trimesters. Serum cortisol seems to be produced throughout the first and second trimesters.

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