Involvement of thyrotropin in photoperiodic signal transduction in mice

Abstract

Local thyroid hormone catabolism within the mediobasal hypothalamus (MBH) by thyroid hormone-activating (DIO2) and -inactivating (DIO3) enzymes regulates seasonal reproduction in birds and mammals. Recent functional genomics analysis in birds has shown that long days induce thyroid-stimulating hormone production in the pars tuberalis (PT) of the pituitary gland, which triggers DIO2 expression in the ependymal cells (EC) of the MBH. In mammals, nocturnal melatonin secretion provides an endocrine signal of the photoperiod to the PT that contains melatonin receptors in high density, but the interface between the melatonin signal perceived in the PT and the thyroid hormone levels in the MBH remains unclear. Here we provide evidence in mice that TSH participates in this photoperiodic signal transduction. Although most mouse strains are considered to be nonseasonal, a robust photoperiodic response comprising induced expression of TSHB (TSH ␤ subunit), CGA (TSH ␣ subunit), and DIO2, and reduced expression of DIO3, was observed in melatonin-proficient CBA/N mice. These responses could not be elicited in melatonin-deficient C57BL/6J, but treatment of C57BL/6J mice with exogenous melatonin elicited similar effects on the expression of the abovementioned genes as observed in CBA/N after transfer to short-day conditions. The EC was found to express TSH receptor (TSHR), and ICV injection of TSH induced DIO2 expression. Finally, we show that melatonin administration did not affect the expression of TSHB, DIO2, and DIO3 in TSHR-null mice. Taken together, our findings suggest that melatonin-dependent regulation of thyroid hormone levels in the MBH appears to involve TSH in mammals.circadian rhythm ͉ melatonin ͉ pars tuberalis ͉ photoperiodism ͉ type 2 and 3 iodothyronine deiodinases O rganisms living outside the tropics detect and predict seasonal changes in day length (photoperiod) to adapt various metabolic and behavioral functions to the environment. This mechanism, called photoperiodism, allows animals to control the timing of reproduction so that they can raise their offspring in spring and summer when food is most abundant. Among vertebrates, birds possess a highly sophisticated photoperiodic mechanism and show robust responses to photoperiodic changes. Taking advantage of the elaborate avian photoperiodic system, we have recently revealed the gene cascade regulating the photoperiodic response of reproduction in Japanese quail (Coturnix japonica) by using a functional genomics approach (1, 2). Exposure to long days induced thyroid-stimulating hormone (TSH), a heterodimer of the TSH ␤ subunit (TSHB), and the common glycoprotein ␣ subunit (CGA, also called TSH ␣ subunit), in the pars tuberalis (PT) of the pituitary gland. TSH triggers the expression of type 2 iodothyronine deiodinase (DIO2) in the ependymal cells (EC) lining the ventrolateral walls of the third ventricle (i.e., the infundibular recess) within the mediobasal hypothalamus (MBH). DIO2 is a thyroid hormoneactivating enzyme that converts the prohormone thyroxine...

Genetic variation of melatonin productivity in laboratory mice under domestication

“…As far as we know, however, the effect of melatonin treatment on the developing gonads of melatonin-deficient mice has not been examined. Ono et al recently reported that a long-day breeder-like photoperiodic signal pathway was retained in laboratory mice (36). The report and our results suggest that mice are potentially a member of long-day breeder family.…”

The saccus vasculosus of fish is a sensor of seasonal changes in day length

“…These results suggest that the SV is involved in the photoperiodic regulation of the gonad in the masu salmon. LD stimulus is known to induce TSH release from the PT in both LD-and SD-breeding birds and mammals, suggesting that PTderived TSH is the 'springtime hormone' [1][2][3] . In this study, we also observed high expression of TSH in the SV of masu salmon under LD conditions.…”

“…Recent studies have uncovered the signal transduction pathway regulating photoperiodism in birds and mammals. The pars tuberalis (PT) of the pituitary gland and the ependymal cells lining ventrolateral walls of the third ventricle within the mediobasal hypothalamus are considered to have critical roles in the regulation of photoperiodism in both birds and mammals [1][2][3] . Long-day (LD)-induced thyrotropin (thyroidstimulating hormone (TSH)) within the PT, a master factor regulating seasonal reproduction, acts on the TSH receptor (TSHR) on the ependymal cells to induce DIO2 expression.…”

“…In mammals, eyes are the only photoreceptive organs, and photoperiodic information received by the eye is transmitted to the pineal organ through the suprachiasmatic nucleus, which serves as the circadian pacemaker. Length of night is encoded by the duration of melatonin secretion from the pineal organ 6 , and melatonin suppresses expression of TSH through the MT1 melatonin receptor in the PT 2,7 . In birds, by contrast, melatonin has little effect on photoperiodic response of gonads 8 .…”

A mammalian neural tissue opsin (Opsin 5) is a deep brain photoreceptor in birds

“…1E). Recently, long-day induction of TSH expression in the pars tuberalis was shown to trigger the photoperiodic response, and the pars tuberalis was reported to be the key organ that relays photoperiodic information to a neuroendocrine output (17,20,21). To examine neural projections in this area, a neural tracer (DiI) was applied to the PVO.…”