Running Head: GONADAL HORMONE EFFECTS ON CIRCADIAN RHYTHMS Revision: R-00043-2006.R1 Gonadal Hormone Effects on Entrained and Free-Running Circadian Activity Rhythms in the Developing Diurnal Rodent, Octodon Degus

The slowly maturing, long-lived rodent Octodon degus (degu) provides a unique opportunity to examine the development of the circadian system during adolescence. These studies characterize entrained and free-running activity rhythms in gonadally intact and prepubertally gonadectomized male and female degus across the first year in order to clarify the impact of sex and gonadal hormones on the circadian system during adolescence. Gonadally intact degus exhibited a delay in the phase angle of activity onset (Ψon) during puberty, which reversed as animals became reproductively competent. Gonadectomy prior to puberty prevented this phase-delay. However, the effect of gonadal hormones during puberty on Ψon does not result from changes to the period of the underlying circadian pacemaker. A sex difference in Ψon and free-running period (τ) emerged several months after puberty; these developmental changes are not likely to be related since the sex difference in Ψon emerged before the sex difference in τ. Changes in the level of circulating hormone cannot explain the emergence of these sex differences since there is a rather lengthy delay between the age at which degus reach sexual maturity and the age at which Ψon and τ become sexually dimorphic. However, postnatal exposure to gonadal hormones is required for sexual differentiation of both Ψon and τ, since these sex differences were absent in pre-pubertally gonadectomized degus. These data suggest that gonadal hormones modulate the circadian system during adolescent development and provide a new model for post-pubertal sexual differentiation of a central nervous system structure.