The annual change in daylength is the major environmental factor regulating the timing of reproduction in many seasonally breeding mammals. The overall objective of the proposed research is to elucidate the neural and endocrine events by which light alters the hypothalamic- pituitary-gonadal axis. Although it is well established that a circadian clock located in the hypothalamic suprachiasmatic nucleus (SCN) plays a central role in measuring the length of the day, little is known about the functional relationship between the operating characteristics of this clock and the photoperiodic reproductive response. In addition, the neuropeptides/neurotransmitters within the circadian clock system responsible for mediating the effects of light on reproduction have not been identified. Recent research efforts have provided novel experimental approaches for altering the circadian clock and/or the photoperiodic response, offering unique opportunities for addressing these issues. The proposed studies will exploit these advances to delineate the mechanisms relating circadian time-keeping to the photoperiodic reproductive response. Three separate experimental strategies involving three different rodent species will be utilized; each species has been chosen because of the advantages it offers in addressing specific questions about the functional relationship between the circadian and reproductive systems. These experiments will involve male rodents, and the circadian rhythm of locomotor activity will be used as a marker of the state of the circadian clock. Serum LH, FSH and testosterone levels, as well as testicular size, will be monitored to assay the state of the reproductive system. In one series of experiments, the period of the circadian clock of golden hamsters will be altered following pharmacological manipulation, during genetic selection or naturally during senescence, to test the hypothesis that changes in circadian period will alter the critical daylength necessary for the stimulation of neuroendocrine-gonadal activity. In a second series of experiments, the photoperiodic reproductive response of Djungarian hamsters will be altered by either genetic or environmental means, to determine if the circadian clock has also been altered. Finally, the role of vasopressin and/or serotonin in he seasonal reproductive response will be determined by examining the photoperiodic response in the Brattleboro rat which is unable to produce vasopressin, or in golden hamsters with lesions of the serotoninergic input to the SCN. It is anticipated that these studies will further delineate the mechanisms responsible for the control of fertility and offer new insights into the effects of light on the reproductive and circadian systems. the completion of these experiments should also provide a better understanding of the physiological and ecological importance of aging for the photoperiodic reproductive response, and of the role played by genetic factors in this response. These studies are anticipated to lead to novel approaches for manipulating seasonal rhythms through pharmacological and non-pharmacological interventions. Such interventions could be important for regulating the seasonal reproductive cycle of economically useful animals as well as for the treatment of various mood disorders that have been associated with seasonal rhythms in humans.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD009885-16
Application #
3311188
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1976-06-30
Project End
1994-04-30
Budget Start
1991-05-01
Budget End
1992-04-30
Support Year
16
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Type
Schools of Arts and Sciences
DUNS #
City
Evanston
State
IL
Country
United States
Zip Code
60201
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Bernard, D J; Abuav-Nussbaum, R; Horton, T H et al. (1999) Photoperiodic effects on gonadotropin-releasing hormone (GnRH) content and the GnRH-immunoreactive neuronal system of male Siberian hamsters. Biol Reprod 60:272-6
Challet, E; van Reeth, O; Turek, F W (1999) Altered circadian responses to light in streptozotocin-induced diabetic mice. Am J Physiol 277:E232-7
Meredith, J M; Turek, F W; Levine, J E (1998) Effects of gonadotropin-releasing hormone pulse frequency modulation on the reproductive axis of photoinhibited male Siberian hamsters. Biol Reprod 59:813-9

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