Royston S E, Bunick D, Mahoney M M
Neuroscience Program, University of Illinois Urbana-Champaign, Urbana, IL, USA.
Medical Scholars Program, University of Illinois College of Medicine, Urbana, IL, USA.
J Neuroendocrinol. 2016 Jan;28(1). doi: 10.1111/jne.12335.
Hormone signalling during critical periods organises the adult circadian timekeeping system by altering adult hormone sensitivity and shaping fundamental properties of circadian rhythmicity. However, the timing of when developmental oestrogens modify the timekeeping system is poorly understood. To test the hypothesis that alterations in postnatal oestrogenic signalling organise adult daily activity rhythms, we utilised aromatase knockout mice (ArKO), which lack the enzyme required for oestradiol synthesis. ArKO and wild-type (WT) males and females were administered either oestradiol (E) or oil (OIL) daily for the first 5 postnatal days (p1-5E and p1-5OIL , respectively) because this time encompasses the emergence of clock gene rhythmicity and light responsiveness in the suprachiasmatic nucleus, a bilateral hypothalamic structure regarded as the 'master oscillator'. After sexual maturation, gonadectomy and exogenous oestradiol supplementation, locomotor parameters were assessed. We determined that altered oestrogenic signalling in early life exerts organisational control over the expression of daily and circadian activity rhythms in adult mice. Specifically, p1-5E reduced total wheel running activity in male and female ArKO and female WT mice but had no effect on WT male activity levels. In females, wheel running was consolidated by p1-5E to the early versus late evening, a phenomenon characteristic of male mice. The time of peak activity was advanced by p1-5E in WT and ArKO females but not males. P1-5E shortened the length of the active phase (alpha) in WT males but had no effect on ArKO males or females of either genotypes. Finally, p1-5E altered the magnitude of photic-induced shifts, suggesting that developmental oestrogenic signalling impacts adult circadian functions. In the present study, we further define both a critical period of development of the adult timekeeping system and the role that oestrogenic signalling plays in the expression of daily and circadian activity rhythms throughout life.
关键时期的激素信号通过改变成年期激素敏感性并塑造昼夜节律的基本特性，来构建成年生物钟系统。然而，发育过程中的雌激素何时改变生物钟系统，目前尚不清楚。为了验证产后雌激素信号变化会构建成年期日常活动节律这一假说，我们使用了芳香化酶基因敲除小鼠（ArKO），这些小鼠缺乏合成雌二醇所需的酶。在出生后的前5天（分别为p1 - 5E和p1 - 5OIL），每天给ArKO和野生型（WT）的雄性和雌性小鼠注射雌二醇（E）或油（OIL），因为这段时间涵盖了视交叉上核中生物钟基因节律性和光反应性的出现，视交叉上核是一个双侧下丘脑结构，被视为“主振荡器”。性成熟、性腺切除和外源性雌二醇补充后，评估运动参数。我们确定，生命早期雌激素信号的改变对成年小鼠日常和昼夜活动节律的表达具有组织性控制作用。具体而言，p1 - 5E降低了雄性和雌性ArKO以及雌性WT小鼠的总转轮活动量，但对WT雄性小鼠的活动水平没有影响。在雌性小鼠中，p1 - 5E使转轮活动集中在傍晚早期而非晚期，这是雄性小鼠的特征现象。WT和ArKO雌性小鼠的活动高峰时间因p1 - 5E而提前，但雄性小鼠没有。P1 - 5E缩短了WT雄性小鼠的活跃期（α）长度，但对ArKO雄性小鼠或两种基因型的雌性小鼠没有影响。最后，p1 - 5E改变了光诱导相移的幅度，表明发育过程中的雌激素信号影响成年生物钟功能。在本研究中，我们进一步明确了成年生物钟系统发育的关键时期，以及雌激素信号在整个生命过程中日常和昼夜活动节律表达中所起的作用。
