Project Description :
Multicellular organisms have endogenous daily (circadian) clocks that control most aspects of their physiology and behavior. On a molecular level, circadian rhythms are generated by cell-autonomous transcriptonal-translational feedback loops involving core "clock genes" and their protein products. In mammals, a master circadian pacemaker is located in the suprachiasmatic nucleus of the hypothalamus (SCN). Among the functions under its control is ovulation, which is triggered by a surge of luteinizing hormone (LH) from the anterior pituitary. The LH surge results from a precisely timed discharge of gonadotropin releasing hormone (GnRH) from the brain on the evening of proestrus.
The neuronal circuits that control the LH surge have been mapped; each receives input from the SCN and each expresses core clock genes. Through use conditional knockouts, we are investigating the role of clock genes in ovulation and the importance of circadian function in particular cell types. Our results indicate that the period of the circadian clocks of different cell types within this circuit must match in order for normal LH surges and regular estrous cycles to occur.
Students will perform histological techniques to analyze ovarian and brain function in animals whose circadian clock has been manipulated by targeting of specific genes. Ovariectomies will be performed and LH concentrations measured in blood samples collected from estrogen-treated mice.