Sánchez de la Peña S, Halberg F, Lakatua D, Ungar F
Prog Clin Biol Res. 1987;227A:421-49.
To assess circadian and circaseptan rhythmic intermodulation, female mice, kept on regimens of 12 hr light (L) alternating with 12 hr of darkness (D) (LD 12:12) were sampled for 1-13 days at six circadian stages. Pineals were removed and homogenized with 0.9% NaCl. Adenohypophyses were bisected and incubated in Krebs-Ringer buffer (KRb) and/or with 10(-7) M melatonin (Mt). Adrenals were bisected and incubated with KRb, with 10(-7) M Mt, with 0.05 IU of ACTH 1-17 (Sy; Hoechst, Italy), or with Sy + 0.025 ml of the aqueous pineal homogenate (APH). ACTH and prolactin (PRL) in adenohypophysis incubation fluid were determined by radioimmunoassay (RIA), and corticosterone in adrenal incubation fluid was determined by RIA or by a fluorometric method. By this chronobiologic approach, time series were collected systematically in the search for predictable variability. Once these series reveal an algorithmically formulatable pattern, with a waveform validated by inferential statistical means, they are graded in terms of complexity as alpha, beta, gamma, and delta rhythms. Spontaneously (alpha-) rhythmic along the 24-h scale is the corticosterone produced by bisected adrenal glands incubated with KRb only, and the Mt content of the APH, in keeping with earlier work. Reactively (beta-) rhythmic is the response, again along the 24-hr scale, of the adrenal to Sy or Mt and the response of the anterior pituitary to Mt at different circadian times. Modulatory (gamma and delta) rhythms characterize the Mt effect on the (beta-rhythmic) adrenal stimulation by Sy. Chronomodulations thus emerge as more or less complete sequences of a decrease, no effect and/or increase; or, rather, as an attenuation, no effect and/or amplification by the pineal, of the pituitary effect upon the adrenal. Linear least-squares rhythmometry, mostly single cosinors, describes and quantifies circadian (alpha, beta, and gamma) and infradian (delta) rhythms in the original series and in the differences in responses [beta - alpha] and [gamma - beta] (P less than 0.001 in each case). These spontaneous alpha, response beta, modulatory gamma, and frequency-divided delta rhythms reveal a collateral neuroendocrine hierarchy, characterized by the pineal feedsideward phenomenon, as a feature of interactions recurring with circadian and infradian frequencies.
为评估昼夜节律和近一周节律的相互调制，将雌性小鼠饲养在12小时光照（L）与12小时黑暗（D）交替（LD 12:12）的环境中，在六个昼夜阶段进行1至13天的采样。取出松果体并用0.9%的氯化钠匀浆。将腺垂体切成两半，在 Krebs-Ringer 缓冲液（KRb）中和/或与10(-7) M褪黑素（Mt）一起孵育。将肾上腺切成两半，与KRb、10(-7) M Mt、0.05 IU促肾上腺皮质激素1-17（Sy；意大利赫斯特公司）或Sy + 0.025 ml松果体水匀浆（APH）一起孵育。通过放射免疫测定法（RIA）测定腺垂体孵育液中的促肾上腺皮质激素和催乳素（PRL），并通过RIA或荧光法测定肾上腺孵育液中的皮质酮。通过这种时间生物学方法，系统地收集时间序列以寻找可预测的变异性。一旦这些序列揭示出一种可通过算法公式化的模式，且其波形经推断统计方法验证，就根据复杂性将它们分为α、β、γ和δ节律。仅与KRb一起孵育的切成两半的肾上腺产生的皮质酮以及APH中的Mt含量在24小时尺度上自发地（α-）呈节律性，这与早期研究一致。反应性地（β-）呈节律性的是肾上腺对Sy或Mt的反应，以及垂体前叶在不同昼夜时间对Mt的反应，同样是在24小时尺度上。调制性（γ和δ）节律表征了Mt对Sy（β节律性）刺激肾上腺的影响。因此，时间调制表现为或多或少完整的减少、无作用和/或增加的序列；或者更确切地说，是松果体对垂体对肾上腺的作用的减弱、无作用和/或放大。线性最小二乘节律测量法，大多为单个余弦曲线，描述并量化了原始序列以及反应差异[β - α]和[γ - β]中的昼夜（α、β和γ）和近昼夜（δ）节律（每种情况下P均小于0.001）。这些自发的α、反应性β、调制性γ和分频δ节律揭示了一种并行的神经内分泌层次结构，其特征为松果体旁馈现象，这是昼夜和近昼夜频率反复出现的相互作用的一个特征。
