Endocrine disruption in human placenta: expression of the dioxin-inducible enzyme, CYP1A1, is correlated with that of thyroid hormone-regulated genes.

Context: Thyroid hormone (TH) is essential for normal development; therefore, disruption of TH action by a number of industrial chemicals is critical to identify. Several chemicals including polychlorinated biphenyls are metabolized by the dioxin-inducible enzyme CYP1A1; some of their metabolites can interact with the TH receptor. In animals, this mechanism is reflected by a strong correlation between the expression of CYP1A1 mRNA and TH-regulated mRNAs.

Central control of circadian phase in arousal-promoting neurons.

Cells of the dorsomedial/lateral hypothalamus (DMH/LH) that produce hypocretin (HCRT) promote arousal in part by activation of cells of the locus coeruleus (LC) which express tyrosine hydroxylase (TH). The suprachiasmatic nucleus (SCN) drives endogenous daily rhythms, including those of sleep and wakefulness. These circadian oscillations are generated by a transcriptional-translational feedback loop in which the Period (Per) genes constitute critical components.

Effects of the duper mutation on circadian responses to light.

The circadian mutation duper in Syrian hamsters shortens the free-running circadian period (τ(DD)) by 2 hours when expressed on a tau mutant (τ(ss)) background and by 1 hour on a wild-type background. We have examined the effects of this mutation on phase response curves and entrainment. In contrast to wild types, duper hamsters entrained to 14L:10D with a positive phase angle.

Duper: a mutation that shortens hamster circadian period.

Three animals born to homozygous tau mutant (τ(ss), "super short") Syrian hamsters showed extremely short free-running periods of locomotor activity (τ(DD) of approximately 17.8 hours). Inbreeding produced 33 such "super duper" animals, which had a τ(DD) of 18.

Lateralization of the central circadian pacemaker output: a test of neural control of peripheral oscillator phase.

To evaluate the contribution of neural pathways to the determination of the circadian oscillator phase in peripheral organs, we assessed lateralization of clock gene expression in Syrian hamsters induced to split rhythms of locomotor activity by exposure to constant light. We measured the ratio of haPer1, haPer2, and haBmal1 mRNA on the high vs. low (H/L) side at 3-h intervals prior to the predicted activity onset (pAO).

Circadian organization of tau mutant hamsters: aftereffects and splitting.

Homozygous tau mutant (tau(ss)) hamsters show an extremely short (20 h) circadian period (tau) that is attributable to altered enzymatic activity of casein kinase 1epsilon. It has been proposed that coupling of constituent circadian oscillators is strengthened in tau(ss) hamsters, explaining their tendency to show strong resetting after prolonged exposure to constant darkness. To evaluate further the circadian organization of tau(ss) hamsters, the authors assessed the extent of shortening of period as an aftereffect of exposure to light:dark cycles whose period (T) is 91% of tau and the ability of constant light to induce splitting.

Behavioral and neurochemical sources of variability of circadian period and phase: studies of circadian rhythms of npy-/- mice.

The cycle length or period of the free-running rhythm is a key characteristic of circadian rhythms. In this study we verify prior reports that locomotor activity patterns and running wheel access can alter the circadian period, and we report that these treatments also increase variability of the circadian period between animals. We demonstrate that the loss of a neurochemical, neuropeptide Y (NPY), abolishes these influences and reduces the interindividual variability in clock period.

Suprachiasmatic regulation of circadian rhythms of gene expression in hamster peripheral organs: effects of transplanting the pacemaker.

Neurotransplantation of the suprachiasmatic nucleus (SCN) was used to assess communication between the central circadian pacemaker and peripheral oscillators in Syrian hamsters. Free-running rhythms of haPer1, haPer2, and Bmal1 expression were documented in liver, kidney, spleen, heart, skeletal muscle, and adrenal medulla after 3 d or 11 weeks of exposure to constant darkness. Ablation of the SCN of heterozygote tau mutants eliminated not only rhythms of locomotor activity but also rhythmic expression of these genes in all peripheral organs studied.

Differential control of peripheral circadian rhythms by suprachiasmatic-dependent neural signals.

Although dependent on the integrity of a central pacemaker in the suprachiasmatic nucleus of the hypothalamus (SCN), endogenous daily (circadian) rhythms are expressed in a wide variety of peripheral organs. The pathways by which the pacemaker controls the periphery are unclear. Here, we used parabiosis between intact and SCN-lesioned mice to show that nonneural (behavioral or bloodborne) signals are adequate to maintain circadian rhythms of clock gene expression in liver and kidney, but not in heart, spleen, or skeletal muscle.

Expression of haPer1 and haBmal1 in Syrian hamsters: heterogeneity of transcripts and oscillations in the periphery.

The molecular biology of circadian rhythms has been extensively studied in mice, and the widespread expression of canonical circadian clock genes in peripheral organs is well established in this species. In contrast, much less information about the peripheral expression of haPer1, haPer2, and haBmal1 is available in Syrian hamsters despite the fact that this species is widely used for studies of circadian organization and photoperiodic responses. Furthermore, examination of oscillating expression of these genes in mouse testis has generated discrepant results, and little is known about gonadal expression of haPer1 and haBmal1 or their environmental control.

Neuropeptide Y differentially suppresses per1 and per2 mRNA induced by light in the suprachiasmatic nuclei of the golden hamster.

Neuropeptide Y (NPY), present in an input pathway to the suprachiasmatic nuclei (SCN), can block the effects of light on circadian rhythms. The authors have studied this interaction using an in vitro brain slice technique. Effects of NPY on light-induced period1 and period2 mRNA in the SCN were examined in vitro following a light pulse during early subjective night.