Thyroid hormone (TH) and estradiol (E2) direct seasonal switches in ovine reproductive physiology. In sheep, as in other mammals and birds, control of thyrotropin (TSH) production by the pars tuberalis (PT) links photoperiod responsiveness to seasonal breeding. PT-derived TSH governs opposite seasonal patterns of the TH deiodinases Dio2/Dio3 expression in tanycytes of the neighboring medio-basal hypothalamus (MBH), which explain the key role of TH. We recently used RNA-Seq to identify seasonal markers in the MBH and define the impact of TH. This impact was found to be quite limited, in terms of number of target genes, and very restricted with regards to neuroanatomical location, as TH specifically impacts genes expressed in tanycytes and hypothalamus, not in the PT. Here we address the impact of E2 on these seasonal markers, which are specifically expressed in either PT, tanycytes or hypothalamus. We also investigate if progesterone (P4) may be involved in timing the seasonal transition to anestrus. Our analysis provides circuit-level insights into the impact of sex steroids on the ewe seasonal breeding cycle. First, seasonal gene expression in the PT is independent of the sex steroid status. The fact that seasonal gene expression in the PT is also TH-independent strengthens the view that the PT is a circannual timer. Second, select tanycytic markers display some level of responsiveness to E2 and P4, which indicates another potential level of feedback control by sex steroids. Third, Kiss1 neurons of the arcuate nucleus are responsive to both TH and E2, which places them at the crossroads of photoperiodic transduction pathway and sex steroid feedback. This provides strong support to the concept that these Kiss1 neurons are pivotal to the long-recognized "seasonal switch in the ability of E2 to exert negative feedback", which drives seasonal breeding.

中文翻译：

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电路级分析确定了母羊季节性育种中性类固醇的靶基因。

甲状腺激素（TH）和雌二醇（E2）指导绵羊生殖生理的季节性变化。在绵羊中，如同在其他哺乳动物和鸟类中一样，通过pars tuberalis（PT）来控制促甲状腺激素（TSH）的产生将光周期响应与季节性繁殖联系起来。PT衍生的TSH控制着相邻的中下丘脑下丘脑（MBH）的单核细胞中TH脱碘酶Dio2 / Dio3表达的相反季节模式，这解释了TH的关键作用。我们最近使用RNA-Seq来识别MBH中的季节性标记并定义TH的影响。在靶基因的数量方面，这种影响被发现是非常有限的，并且在神经解剖位置方面非常有限，因为TH会特异性地影响单核细胞和下丘脑而不是PT中表达的基因。在这里，我们探讨E2对这些季节性标记的影响，在PT，单核细胞或下丘脑中特异性表达。我们还调查了孕酮（P4）是否可能参与了季节性向发情期的过渡。我们的分析为性类固醇对母羊季节性繁殖周期的影响提供了回路方面的见识。首先，PT中的季节性基因表达与性类固醇状态无关。PT中季节性基因表达也与TH无关的事实强化了以下观点：PT是一个年度计时器。其次，选择的单核细胞标记物对E2和P4表现出一定程度的反应性，这表明性类固醇可以控制反馈的另一个潜在水平。第三，弓形核的Kiss1神经元对TH和E2都有反应，这使它们处于光周期传导途径和性类固醇反馈的十字路口。