Corticosteroid binding globulin control of HPA axis sensitivity and sexual dimorphism

Mark Nixon, University of Edinburgh

 

Aims

COVID-19 has significantly impacted the ability of researchers to forge collaborations and publish work in a timely manner. As an early career researcher who has recently become an independent PI, these are crucial milestones in my career development. This application seeks funds to complete collaborative work that has been negatively impacted by the pandemic and thus ensure accelerated publication. This collaboration involves world-leading groups in steroid biology based at the University of British Columbia (UBC), and presents an exciting opportunity to merge our expertise in the study of binding globulin control of stress and sex steroid action, and regulation of hypothalamic pituitary adrenal axis sensitivity.

The objectives of this application are therefore:

• To strengthen the links between our labs at the University of Edinburgh and UBC, establishing a new collaboration with Prof Victor Viau and supporting our existing collaboration with Prof Geoff Hammond.
• To expedite publication of this novel collaborative work, a crucial milestone for an early career researcher.
• To drive and enable future innovative research into multi-steroid profiling in rodents through wide-spread dissemination of our methods.

Support in completing these aims will significantly lessen the adverse impact that COVID-19 has had on my ability to effectively collaborate and publish.

 

Evaluation

The application sought funds to complete collaborative work between my group and that of Prof Victor Viau at the University of British Columbia (UBC) that had been negatively impacted by the pandemic. The aims of the application were:

• To strengthen the links between our labs at the University of Edinburgh and UBC, establishing a new collaboration with Prof Victor Viau and supporting our existing collaboration with Prof Geoff Hammond.
• To expedite publication of this novel collaborative work, a crucial milestone for an early career researcher.
• To drive and enable future innovative research into multi-steroid profiling in rodents through wide-spread dissemination of our methods.

The award allowed successful quantification of total and free glucocorticoids from terminally obtained blood samples in rats, as well as implementation and quantification of novel multi-steroid analyses in the same samples. Briefly, the study comprised the use of male and female rats to determine the importance of the glucocorticoid binding protein CBG (corticosteroid binding globulin) in mediating sexual dimorphism in adrenal development. Through my labs expertise in free steroid quantification and our local links to the University of Edinburgh Mass Spectrometry Facility, we established and validated a proof-of-concept protocol to assess both total and unbound/free glucocorticoid levels in rat plasma. Award of the grant allowed us to successfully extract and analyse experimental samples from the Viau group. No significant difficulties were encountered, and we are pleased to report that this work has now been published (Oct 2022; DOI: 10.1210/endocr/bqac152) and the grant award acknowledged for it’s significant contribution. As the major evaluation endpoint, publication has served to strengthen our links with the groups in UBC, highlight novel determinants of adrenal development, and brought to the field of steroid biology a reliable, sensitive method for multi-steroid quantification.

 

Grant awarded: £4,005.00