The annual change in day length is the major environmental factor regulating the timing of reproduction in many seasonally breeding mammals. Both the circadian clock located in the hypothalamic suprachiasmatic nucleus and the pineal melatonin rhythm play a central role in relaying information about length of the day to the neuroendocrine-gonadal axis. Despite the fact that a variety of age-related changes in the circadian clock system have now been well documented in mammals, including changes in the response to the entraining effects of the light dark cycle and dampening of the pineal melatonin rhythm, very little is known about how age-related changes in circadian function may impact on the response of seasonally breeding animals to changes in day length. In the proposed studies, golden and Siberian hamsters will be utilized to test various hypotheses regarding 1) the effects of age on the photoperiodic control of neuroendocrine-gonadal activity and the circadian clock system, 2) how aging alters the interactions between the various components of the photoperiodic time measuring system and 3) how day length influences the effects of age on circadian rhythmicity. For all studies the rhythm of locomotor activity will be used as a marker for the state of the circadian clock system. Serum LH, FSH and testosterone levels, as well as testicular size, will be monitored to assay the state of the reproductive system, and in some studies serum melatonin levels will be determined. Various studies are proposed to determine how aging may effect 1) the critical day length for the photoperiodic response and the entrainment to different light-dark cycles, 2) the pattern of melatonin secretion, 3) the response of the neuroendocrine-gonadal axis to melatonin, 4) the sensitivity of the neuroendocrine-gonadal axis to light intensity and 5) feedback relationships in the circadian clock system and in the neuroendocrine-gonadal axis. Other studies will determine if age-related changes in the photoperiodic response can be blocked by stimuli that alter the circadian temporal organization. Taken together, the proposed studies are expected to yield new information about the physiological mechanisms that underlie age related changes in the photoperiodic response. Age related changes in the way hamsters respond to changes in the length of the day offer new avenues for elucidating the physiological and cellular mechanisms that underlie the generation of circadian rhythms as well as the photic control of the hypothalamic-pituitary-gonadal axis. In view of recent demonstrations that the pattern of human endocrine rhythms is also influenced by the length of the day, the results of the proposed studies are expected to increase our understanding of how age-related changes in the human neuroendocrine system may be affected by the seasonal change in day length; such information may also lead to new treatments of mood disorders that have been associated with seasonal rhythms.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD009885-20
Application #
2673427
Study Section
Special Emphasis Panel (ZRG2-BPO (01))
Project Start
1976-06-30
Project End
2001-06-30
Budget Start
1998-07-01
Budget End
1999-06-30
Support Year
20
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Neurology
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
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Challet, E; Bernard, D J; Turek, F W (1999) Gold-thioglucose-induced hypothalamic lesions inhibit metabolic modulation of light-induced circadian phase shifts in mice. Brain Res 824:18-27
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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