Regulation of human (adrenal) androgen biosynthesis-New insights from novel throughput technology studies

Udhane, Sameer Sopanrao; Flück, Christa Emma (2016). Regulation of human (adrenal) androgen biosynthesis-New insights from novel throughput technology studies. Biochemical pharmacology, 102, pp. 20-33. Elsevier 10.1016/j.bcp.2015.10.010

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Androgens are precursors for sex steroids and are predominantly produced in the human gonads and the adrenal cortex. They are important for intrauterine and postnatal sexual development and human reproduction. Although human androgen biosynthesis has been extensively studied in the past, exact mechanisms underlying the regulation of androgen production in health and disease remain vague. Here, the knowledge on human androgen biosynthesis and regulation is reviewed with a special focus on human adrenal androgen production and the hyperandrogenic disorder of polycystic ovary syndrome (PCOS). Since human androgen regulation is highly specific without a good animal model, most studies are performed on patients harboring inborn errors of androgen biosynthesis, on human biomaterials and human (tumor) cell models. In the past, most studies used a candidate gene approach while newer studies use high throughput technologies to identify novel regulators of androgen biosynthesis. Using genome wide association studies on cohorts of patients, novel PCOS candidate genes have been recently described. Variant 2 of the DENND1A gene was found overexpressed in PCOS theca cells and confirmed to enhance androgen production. Transcriptome profiling of dissected adrenal zones established a role for BMP4 in androgen synthesis. Similarly, transcriptome analysis of human adrenal NCI-H295 cells identified novel regulators of androgen production. Kinase p38α (MAPK14) was found to phosphorylate CYP17 for enhanced 17,20 lyase activity and RARB and ANGPTL1 were detected in novel networks regulating androgens. The discovery of novel players for androgen biosynthesis is of clinical significance as it provides targets for diagnostic and therapeutic use.

Item Type:

Journal Article (Review Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Endokrinologie / Diabetologie / Metabolik (Pädiatrie)
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine

UniBE Contributor:

Udhane, Sameer Sopanrao and Flück, Christa Emma

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0006-2952

Publisher:

Elsevier

Language:

English

Submitter:

André Schaller

Date Deposited:

02 May 2016 10:57

Last Modified:

30 Sep 2017 09:13

Publisher DOI:

10.1016/j.bcp.2015.10.010

PubMed ID:

26498719

Uncontrolled Keywords:

Adrenarche; Androgens; Backdoor pathway; GWAS; High throughput technologies; Polycystic ovary syndrome (PCOS); Regulation of steroidogenesis; Tissue and cell profiling

BORIS DOI:

10.7892/boris.79276

URI:

https://boris.unibe.ch/id/eprint/79276

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