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EMSG52-MRC: Steroidogenesis and inter species comparison literature review

Principal Investigator

Prof. Richard Sharpe
Centre for Reproductive Biology
The Queen's Medical Research Institute
47 Little France Crescent
Edinburgh, EH16 4TJ
United Kingdom
Tel: +44-131-242-6387
Fax: +44-131-242-6231


Prof. Richard Sharpe - Centre for Reproductive Biology, UK
Prof. Ian Mason - Clinical Biochemistry, UK
Dr. Hayley Scott - Plant Breeding & Wheat Breeder, UK


Masculinisation depends on adequate production of testosterone by the fetal testis within a specific’male programming window’. Disorders resulting from subtle deficiencies in this process are common in humans and environmental exposures/lifestyle could contribute causally as common therapeutic and environmental compounds can affect steroidogenesis. This evidence derives mainly from rodent studies, but as there are major species differences in regulation of steroidogenesis in the fetal testis, this may not always be a guide to potential effects in the human. As well as direct study of the effects of compounds on steroidogenesis, information also derives from study of masculinisation disorders that result from mutations in genes in pathways regulating steroidogenesis. This review addresses this issue by critically reviewing the comparative timing of production and regulation of steroidogenesis in the fetal testis of humans and of rodents and its susceptibility to disruption; where there is limited information for the fetus, evidence from effects on steroidogenesis in the adult testis is considered. There are a number of fundamental regulatory differences between the human and rodent fetal testis, most notably in the importance of paracrine versus endocrine drives during masculinisation such that inactivating LH receptor mutations block masculinisation in humans but not in rodents. Other large differences involve the steroidogenic response to estrogens and GnRH analogs and possibly phthalates, whereas for other compounds there may be differences in sensitivity to disruption (ketoconazole). This comparison identifies steroidogenic targets that are either vulnerable (mitochondrial cholesterol transport, CYP11A, CYP17) or not (cholesterol uptake) to chemical interference.

Related Publications

Scott M.H., Mason J. I., Sharpe M.R. 2009. Steroidogenesis in the Fetal Testis and Its Susceptibility to Disruption by Exogenous Compounds. Endocrine Reviews 30(7):0000-0000.

Timeline: September 2008 > December 2008

LRI funding: € 40.000


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