Maternal photoperiod programs hypothalamic thyroid status via the fetal pituitary gland

Abstract

In wild mammals, offspring development must anticipate forthcoming metabolic demands and opportunities. Within species, different developmental strategies may be used, dependent on when in the year conception takes place. This phenotypic flexibility is initiated before birth and is linked to the pattern of day length (photoperiod) exposure experienced by the mother during pregnancy. This programming depends on transplacental communication via the pineal hormone melatonin. Here, we show that, in the Siberian hamster (Phodopus sungorus), the programming effect of melatonin is mediated by the pars tuberalis (PT) of the fetal pituitary gland, before the fetal circadian system and autonomous melatonin production is established. Maternal melatonin acts on the fetal PT to control expression of thyroid hormone deiodinases in ependymal cells (tanycytes) of the fetal hypothalamus, and hence neuroendocrine output. This mechanism sets the trajectory of reproductive and metabolic development in pups and has a persistent effect on their subsequent sensitivity to the photoperiod. This programming effect depends on tanycyte sensitivity to thyroid stimulating hormone (TSH), which is dramatically and persistently increased by short photoperiod exposure in utero. Our results define the role of the fetal PT in developmental programming of brain function by maternal melatonin and establish TSH signal transduction as a key substrate for the encoding of internal calendar time from birth to puberty.photoperiodism | developmental programming | hypothalamus | pars tuberalis | thyroid

Maternal photoperiodic programming enlightens the internal regulation of thyroid‐hormone deiodinases in tanycytes

“…Functional studies show that the developmental trajectory set by the prenatal photoperiodic experience continues in juveniles pinealectomised or reared in constant light, and thus in the absence of postnatal melatonin . In our recent study, we observed that juvenile Siberian hamsters gestated in either LP (16 h L day ‐1 ) or SP (8 h L day ‐1 ) and transferred to IP (14 h L day ‐1 ) at weaning (Figure A) presented melatonin peaks of similar duration, regardless of their experience (Figure B), as observed previously . These results suggest that MPP does not arise from altered circulating melatonin patterns in juveniles, although it may result from a change in their sensitivity to melatonin signalling.…”

“…increasing doses of TSH previously shown to cause minimal effects on dio2 expression . Accordingly, 0.5 mIU of TSH induced dio2 mRNA expression in both LP‐IP and SP‐IP animals, whereas 1 mIU of TSH further increased dio2 mRNA expression in SP‐IP animals, although not in the LP‐IP group, demonstrating a decreased sensitivity to TSH in LP‐IP animals, which is an effect that was not associated with changes in TSH‐r mRNA expression, nor circulating TH feedback on deiodinase expression . This change in the level of dio2 expression to a given TSH mRNA level was recently reported in a study exploring critical photoperiods in sheep .…”

“…LP‐gestated newborns expressed higher TSHβ in the PT, together with a higher dio2 mRNA level in the tanycytes than those gestated in SP, indicating that the maternal melatonin binding to foetal pituitary and the PT‐hypothalamic retrograde communication lead to regulation of local TH metabolism in the newborn's tanycytes (Figure B). Dio3 gene expression was first observed by mid‐lactation only in the SP animals …”

“…Maternal photoperiodic programming neuroendocrine pathway. A, Timeline and photoperiodic conditions used to explore the effects of maternal photoperiodic programming . Animals gestated and maintained during lactation in either long photoperiod ( LP : 16:8 h light/dark) or short photoperiod ( SP : 8:16 h light/dark) are maintained in the same photoperiod or transferred to an intermediate photoperiod ( IP : 14:10 h light/dark) at weaning.…”

“…We recently investigated the neuroendocrine mechanisms involved in the MPP response with the working hypothesis that the neuroendocrine TSH/dio system downstream of melatonin will reflect the programming effect of photoperiodic history lived in utero. Using a developmental approach to induce the MPP phenomenon, Siberian hamsters gestated and raised in LP or SP were transferred at weaning to IP (LP‐IP and SP‐IP, respectively) (Figure A). LP‐gestated newborns expressed higher TSHβ in the PT, together with a higher dio2 mRNA level in the tanycytes than those gestated in SP, indicating that the maternal melatonin binding to foetal pituitary and the PT‐hypothalamic retrograde communication lead to regulation of local TH metabolism in the newborn's tanycytes (Figure B).…”