Gonadal hormone effects on entrained and free-running circadian activity rhythms in the developing diurnal rodent Octodon degus

Abstract

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 of life 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 (⌿on) during puberty, which reversed as animals became reproductively competent. Gonadectomy before puberty prevented this phase delay. However, the effect of gonadal hormones during puberty on ⌿on does not result from changes in the period of the underlying circadian pacemaker. A sex difference in ⌿on and free-running period () emerged several months after puberty; these developmental changes are not likely to be related, since the sex difference in ⌿on emerged before the sex difference in . Changes in the levels of circulating hormones 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 ⌿on and become sexually dimorphic. However, postnatal exposure to gonadal hormones is required for sexual differentiation of ⌿ on and , since these sex differences were absent in prepubertally gonadectomized degus. These data suggest that gonadal hormones modulate the circadian system during adolescent development and provide a new model for postpubertal sexual differentiation of a central nervous system structure. adolescent development; puberty; phase angle; tau; sexual differentiation ALTHOUGH DEVELOPMENTAL CHANGES within the circadian system have been well described, the existing research has focused primarily on changes during prenatal and early postnatal development or changes that occur with advanced age (23, 33). Adolescent development has received comparably little attention, despite the well-known phase delays in circadian rhythms exhibited by human adolescents (2, 3, 5, 10). There is little doubt that social factors play an important part in these developmental changes (e.g., increased academic responsibilities lead to later bedtimes); however, the phase delay in circadian rhythms is positively correlated with sexual maturity (5), which would suggest that gonadal hormones modulate the circadian system during adolescent development (6,29,32).It is possible that the phase delay in the circadian rhythms in human adolescents is the result of gonadal hormones acting to lengthen the endogenous period of the central circadian pacemaker (2). This hypothesis has not received much empirical support; although free-running period () appears to be longer in adolescent humans than in adults (2, 7), these age groups have not been directly compared in the same experiment. The rodent models commonly used...

Adolescent Changes in the Homeostatic and Circadian Regulation of Sleep

“…data]. Similarly, a careful developmental analysis of the degu did not find changes in during puberty at the age of the delay in entrained phase [13] .…”

“…This discrepancy between the results of human, rat, and degu studies might be explained by the presence or absence of light exposure during the free-running protocols. The pubertal rodents were exposed to constant darkness (DD, [13] ) or very dim red light (0.1 lx RR [17] ) while was measured. Whereas humans were exposed to a light cycle (LD; 20 vs. 0 lx) with a day length (T) that was outside of the range of entrainment for the circadian system (T = 28 h) [44] .…”

“…To test this hypothesis, we reviewed data from nine studies that examined the daily rhythms of mammals during pubertal development [12][13][14][15][16][17][18][19][20] . We inferred the timing of puberty by referencing universal markers (the initiation of spermatogenesis and ovulation) discussed in previously published reproductive studies for each species [21][22][23][24][25] .…”

“…This review found evidence for delayed circadian phase during puberty in all five species studied: Macaca mulatta (rhesus macaque [12] ), Octodon degus (degu [13][14][15][16] ), Rattus norvegicus (laboratory rat [16,17] ), Mus musculus (laboratory mouse [18,19] ), and Psammomys obesus (fat sand rat [20] ). Overall, this evidence indicated that the delayed timing of sleep during human adolescence is likely to represent a developmental change common across mammalian species ( table 1 ).…”

“…First, many of the studies were not intentionally designed to observe this phenomenon, and therefore they only measured circadian phase at 1 or 2 pubertal time points [13,15,[18][19][20] . This inconsistency makes it difficult to estimate and compare the magnitude of developmental change across species or to verify that rhythms that did not show a significant developmental change were not missed by the sampling window (e.g.…”