Deciphering the role of thyroid hormones in season.. (ThyroRepro)
Deciphering the role of thyroid hormones in seasonal reproduction
Date du début: 1 août 2012,
Date de fin: 31 juil. 2016
Most mammals living at temperate latitudes exhibit seasonal reproduction, which is synchronized by photoperiod through the central action of melatonin. In the ewe this translates into the initiation of the breeding season as day-length shortens while the anestrus season is triggered by the photoperiod lengthening, which occurs at the end of winter. We recently characterized a complex pathway by which melatonin acts in the rostral part of the pituitary, known as the pars tuberalis, to yield a local increase of triiodothyronine (T3) within the adjacent medio-basal hypothalamus (MBH). This mechanism accounts for early observations that T3 increase within this region is mandatory for anestrus to occur. Building on these findings, this research program aims at a thorough characterization of the downstream events which ultimately tie the local increase in T3 to the shutdown of the gonadotropic axis. I propose a transcriptomics approach to reveal T3 target genes within the MBH and decipher how their photoperiodic control eventually impacts on the activity of GnRH neurons. Since the long-term objective of this work is to obtain out-of-season lambing without adverse hormonal treatments, the identification of T3 target genes will provide us with potential levers. The use of genetic databases in different ovine breeds presenting varying degrees of seasonality will help to assess the physiological role of these genes and lead to an improved genetic selection. The increase of T3 within the MBH requires the presence of its precursor, the thyroxine T4, in the cerebrospinal fluid. Since T4 gains access to the CSF through the choroid plexuses, the latter constitute another potential target to modulate seasonal reproduction. Therefore, we will also evaluate the impact of photoperiod on the transcriptome of this tissue. These data will provide insights into the molecular mechanisms of photoperiodism and offer potential avenues to develop innovative breeding strategies.
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