Babu G N, Marco J, Bona-Gallo A, Gallo R V
Department of Physiology and Neurobiology, University of Connecticut, Storrs.
Neuroendocrinology. 1988 Mar;47(3):249-58. doi: 10.1159/000124919.
The objective of this study was to determine whether the negative feedback action of ovarian steroids on pulsatile luteinizing hormone (LH) release in the diestrous 1 (D1)-diestrous 2 (D2) interval of the rat estrous cycle is mediated by endogenous opioid peptides (EOPs), by examining the pulsatile LH release response to naloxone infusions in the presence or absence of D1-D2 levels of estradiol (E2) and progesterone (P). As plasma E2 and P levels increased between D1 and D2, mean blood LH levels decreased due solely to a decrease in LH pulse amplitude as frequency remained stable. However, ovariectomy increased both parameters of pulsatile LH release, indicating the effect of loss of ovarian steroid-negative feedback in this interval. Replacement of D1-D2 plasma levels of E2 and P restored D2 values for both parameters of pulsatile LH release, and E2 + P did not alter in vivo pituitary responsiveness to LH-releasing hormone (LHRH). In ovariectomized rats lacking the negative feedback provided by E2 + P in this cycle interval, continuous infusion of naloxone caused a further dose-dependent augmentation in both LH pulse amplitude and frequency. This stimulatory action of naloxone was prevented by simultaneous infusion with morphine, and was not associated with any change in in vivo pituitary responsiveness to LHRH, indicating that this was an action exerted through centrally located EOP receptors. Naloxone also increased both parameters of pulsatile LH release in E2 + P-treated rats. However, the magnitudes of the naloxone-induced increments in LH pulse amplitude and frequency in ovariectomized, steroid-treated rats were not greater than those seen in ovariectomized, nonsteroid-treated rats given naloxone versus saline. In addition, mean values for both parameters of pulsatile LH secretion during EOP receptor blockade in steroid-treated rats were reduced when compared to values in ovariectomized, nonsteroid-treated rats infused with naloxone. Thus the stimulatory effect of naloxone on pulsatile LH release was similar in the presence or absence of the negative feedback action of D1-D2 plasma levels of E2 + P. This indicates that the negative feedback effect of E2 + P on pulsatile LH release in this interval is not mediated by EOPs whose actions are blocked by naloxone.
本研究的目的是通过检测在有或无动情周期间情期1（D1）-间情期2（D2）水平的雌二醇（E2）和孕酮（P）存在时，纳洛酮输注对促黄体生成素（LH）脉冲式释放的反应，来确定大鼠动情周期D1-D2期间卵巢甾体激素对LH脉冲式释放的负反馈作用是否由内源性阿片肽（EOPs）介导。随着D1和D2之间血浆E2和P水平升高，平均血LH水平仅因LH脉冲幅度降低而下降，频率保持稳定。然而，卵巢切除增加了LH脉冲式释放的两个参数，表明在此期间卵巢甾体激素负反馈缺失的影响。补充D1-D2血浆水平的E2和P可使LH脉冲式释放的两个参数恢复到D2值，且E2 + P并未改变体内垂体对促性腺激素释放激素（LHRH）的反应性。在该周期区间缺乏E2 + P提供的负反馈的去卵巢大鼠中，持续输注纳洛酮导致LH脉冲幅度和频率进一步呈剂量依赖性增加。纳洛酮的这种刺激作用可被同时输注吗啡所阻断，且与体内垂体对LHRH的反应性的任何变化无关，表明这是通过位于中枢的EOP受体发挥的作用。纳洛酮也增加了E2 + P处理大鼠LH脉冲式释放的两个参数。然而，去卵巢、甾体激素处理大鼠中纳洛酮诱导的LH脉冲幅度和频率增加的幅度并不大于给予纳洛酮而非生理盐水的去卵巢、非甾体激素处理大鼠。此外，与输注纳洛酮的去卵巢、非甾体激素处理大鼠相比，甾体激素处理大鼠在EOP受体阻断期间LH脉冲式分泌的两个参数的平均值降低。因此，无论有无D1-D2血浆水平的E2 + P的负反馈作用，纳洛酮对LH脉冲式释放的刺激作用相似。这表明在此期间E2 + P对LH脉冲式释放的负反馈作用不是由其作用被纳洛酮阻断的EOPs介导的。
