Connors-BRI Symposium

Incorporating Sex as Biologic Variable to Advance Health

May 24, 2021 | 3-5PM

Virtual Event

Khadijeh (Shadi) Gholami, PhD

Brigham and Women’s Hospital
Medicine/Endocrinology, Diabetes & Hypertension


Inconsistencies have been reported on the effect of sex on aldosterone levels leading to substantial clinical confusion. The reasons for these sex-associated inconsistencies, are uncertain but include: 1) estrogen and/or its receptor modulating target gene responses to mineralocorticoid receptor (MR) activation and 2) aldosterone secretagogues’ levels. This study’s goal was to determine whether aldosterone’s biosynthesis also differed by sex. Two approaches were used. First, circulating plasma renin activity (PRA) and aldosterone were measured. Both were significantly higher in males. Secondly, using rat zona glomerulosa (ZG) cells, we assessed three ex-vivo areas:1) activity of an early step in aldosterone’s biosynthesis (CYP11A1); 2) activity of a late step (CYP11B2); and 3) the status of the MR mediated, ultrashort-feedback-loop. Female versus male rats had increased CYP11A1 activity (increased pregnenolone levels) and expression but did not differ in CYP11B2activity (aldosterone/corticosterone levels) and expression. Activating the ZG’s MR (thereby activating the ultrashort-feedback-loop) reduced CYP11B2’s activity similarly in males and females. Ex-vivo, these molecular effects were accompanied, in females, by lower aldosterone basally but higher aldosterone with angiotensin II stimulation. In conclusion, we documented that not only was there a sex-mediated difference in the activity of aldosterone’s biosynthesis, but also these differences at the molecular level, likely explain the variable reports on aldosterone’s circulating levels. Basally, both in-vivo and ex-vivo, males had higher aldosterone levels, likely secondary to higher aldosterone secretagogue levels (e.g., PRA). However, in response to acute stimulation, aldosterone levels are higher in females because of the greater activity of their CYP11A1.


3PM – Welcome Remarks
3:05PM – Keynote Address
3:45PM – Featured Short Talks
4:20PM – Lightning Talks
4:50PM – Closing Remarks

Keynote Speaker

Janine Austin Clayton, MD

Janine Austin Clayton, M.D., Associate Director for Research on Women’s Health and Director of the Office of Research on Women’s Health (ORWH) at the National Institutes of Health (NIH), is the architect of the NIH policy requiring scientists to consider sex as a biological variable across the research spectrum. This policy is part of NIH’s initiative to enhance reproducibility through rigor and transparency. As co-chair of the NIH Working Group on Women in Biomedical Careers with NIH Director Dr. Francis Collins, Dr. Clayton also leads NIH’s efforts to advance women in science careers.

Prior to joining the ORWH, Dr. Clayton was the Deputy Clinical Director of the National Eye Institute (NEI) for seven years. A board-certified ophthalmologist, Dr. Clayton’s research interests include autoimmune ocular diseases and the role of sex and gender in health and disease. She is the author of more than 120 scientific publications, journal articles, and book chapters.
Dr. Clayton, a native Washingtonian, received her undergraduate degree with honors from Johns Hopkins University and her medical degree from Howard University College of Medicine. She completed a residency in ophthalmology at the Medical College of Virginia. Dr. Clayton completed fellowship training in cornea and external disease at the Wilmer Eye Institute at Johns Hopkins Hospital and in uveitis and ocular immunology at NEI.

Dr. Clayton has received numerous awards, including the Senior Achievement Award from the Board of Trustees of the American Academy of Ophthalmology in 2008 and the European Uveitis Patient Interest Association Clinical Uveitis Research Award in 2010. She was selected as a 2010 Silver Fellow by the Association for Research in Vision and Ophthalmology. In 2015, she was awarded the American Medical Women’s Association Lila A. Wallis Women’s Health Award and the Wenger Award for Excellence in Public Service. Dr. Clayton was granted the Bernadine Healy Award for Visionary Leadership in Women’s Health in 2016. She was also selected as an honoree for the Woman’s Day Red Dress Awards and the American Medical Association’s Dr. Nathan Davis Awards for Outstanding Government Service in 2017.