Circadian Clock Gene Has Different Effects in Men and Women

MedicalResearch.com Interview with:

Lauren Douma, Ph.D. Postdoctoral Fellow University of Florida Department of Medicine Division of Nephrology, Hypertension, and Renal Transplantation Gainesville, FL 32610

Dr. Douma

Lauren Douma, Ph.D.
Postdoctoral Fellow
University of Florida
Department of Medicine
Division of Nephrology, Hypertension, and Renal Transplantation
Gainesville, FL 32610

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: Our internal circadian clock not only controls our sleep/wake cycle, but also many other physiological functions including rhythms in body temperature, heart rate, and blood pressure. During the day when we are active our blood pressure peaks and at night when we are asleep our blood pressure dips. Certain individuals do not experience this dip in their blood pressure at night and are referred to as non-dippers. Non-dippers have an increased risk for heart and kidney disease. Previously, our lab has shown that if we knock out a core circadian clock gene (PER1) in male mice, they develop non-dipping hypertension on a treatment that mimics salt-sensitive hypertension. In the current study, we examined the effect of knocking out this circadian clock gene in female mice. We found that female mice without the PER1 gene do not develop the non-dipping hypertension that the males develop. Female mice without PER1 maintain their circadian rhythms of blood pressure, including the dip in their blood pressure at night even with the same treatment that the males received to mimic salt-sensitive hypertension.

MedicalResearch.com: What should readers take away from your report?

Response: Knock out of the circadian clock gene PER1 has different effects in males and females. Our results match previously reported data that premenopausal women have a lower incidence of non-dipping hypertension than males of the same age. Interestingly, after menopause, women have a higher incidence of non-dipping hypertension than men. These sex differences in the incidence of non-dipping hypertension may be partially due to sex differences in our circadian clocks.

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: Determining why the circadian clock works differently in men and women is critical not only for the development of novel therapeutics, but also for determining the best course of treatment for each individual. Our study is the first to look at the circadian rhythms of blood pressure in female mice without a core circadian clock gene. The majority of research reported to date is almost exclusively in male animals. In order to fully understand the cellular mechanisms that drive these sex differences in physiological functions, more research will need to be performed looking at both male and female animals. 

MedicalResearch.com: Is there anything else you would like to add?

Response: This research was supported by National Institutes of Health (NIH) Grants R01-DK-109570, an American Heart Association Grant-in-Aid, a grant from the American Society of Nephrology Foundation for Research (M. L. Gumz), an American Heart Association Postdoctoral Fellowship Grant 18POST34030210 (L. Douma), NIH Grant T32-DK-104721 awarded to the University of Florida (UF) Division of Nephrology (L. Douma), and NIH Grant T32-HL-083810 awarded to the UF Hypertension Center (K. Solocinski and G. R. Crislip).

Citation:

Douma, L. G., Solocinski, K., Holzworth, M. R., Crislip, G. R., Masten, S. H., Miller, A. H., Cheng, K.Y., Lynch, I.J., Cain, B.D., Wingo, C.S., Gumz, M.L. (2019). Female C57BL/6J mice lacking the circadian clock protein PER1 are protected from nondipping hypertension.American Journal of Physiology. Regulatory, Integrative and Comparative Physiology316(1), R50–R58. http://doi.org/10.1152/ajpregu.00381.2017

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