Language

English (en)

Date of Award

Summer 8-2019

Author's School

College of Arts & Sciences

Author's Department

Biology

Degree Name

Bachelor of Arts (A.B.)

Restricted/Unrestricted

Unrestricted

Abstract

Most biological processes are regulated by an internal circadian rhythm. This body clock synchronizes daily rhythms in physiology with the environment. Circadian outputs can differ between females and males, but the underlying mechanisms for these differences are unknown. Glucocorticoids, a class of circadian stress hormones in vertebrates, provide a model for studying sexual dimorphisms in circadian timing. Female rodents show a higher mean and peak-to-trough amplitude of corticosterone than males. This is most prevalent during proestrus when estrogen levels are high. To test the hypothesis that male-female differences in daily corticosterone secretion arise within circadian cells in the brain, we recorded gene expression in real-time from cultured paraventricular nucleus (PVN) and suprachiasmatic nucleus (SCN) of male and proestrus-locked, female mice. Using PERIOD2-luciferase knock-in (PER2::LUC) mice, we measured bioluminescence with a photomultiplier tube (PMT) and compared circadian parameters of PER2 expression. Both the SCN and PVN showed intrinsic circadian rhythms in PER2 expression, but no sex differences in amplitude, period, or phase of PER2 rhythms. We next tested if estrogen is necessary for sex differences in circadian timing. Addition of estrogen to the recording media produced a phase delay in the explanted PVN and SCN, but no sex differences in their circadian amplitude, period, or phase. Preliminary recordings from corticotropin-releasing hormone (CRH) neurons of the PVN in vivo revealed circadian rhythms and will allow us to test whether sex differences exist in different cell types along the hypothalamic-pituitary-adrenal axis. We conclude that the sex differences in daily glucocorticoid secretion originate downstream of the SCN and PVN. These results are relevant to diseases associated with disruption of daily rhythms in hormone release and the cellular determination of sex differences in circadian timing.

Mentor

Erik Herzog, PhD

Additional Advisors

Jeff R. Jones, PhD

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