MohanKumar P S, MohanKumar S M, Arbogast L, Quadri S K, Voogt J L
Department of Physiology, University of Kansas Medical Center, Kansas City 66160, USA.
Proc Soc Exp Biol Med. 1998 Apr;217(4):461-5. doi: 10.3181/00379727-217-44258.
Prolactin (PRL) secretion is under the inhibitory regulation of the tuberoinfundibular dopaminergic (TIDA) system. Short-term elevation in PRL levels has been shown to increase the activity of TIDA neurons, however, the responsiveness of TIDA neurons to chronically elevated serum PRL levels is controversial. The purpose of this study was to investigate the effects of prolonged elevations of serum PRL on TIDA neuronal activity. Female Sprague-Dawley rats (2-3 months old) were ovariectomized and implanted (s.c.) with haloperidol (HAL), a dopamine receptor antagonist for 6 or 9 months to produce hyperprolactinemia. Ovariectomized, sham-implanted rats were used as controls. Other groups of intact rats were implanted with HAL or sham-implanted for 9 months and then were implanted with PRL-producing MMQ cells for 6 weeks to further increase circulating PRL levels. TIDA neuronal activity was measured in terms of tyrosine hydroxylase (TH) activity in the stalk-median eminence and was correlated with changes in serum PRL levels. After 6 months of treatment, TH activity in HAL-treated rats was 130% higher than that in the control rats. After 9 months of treatment, TH activity in HAL-treated rats was 81% higher than that in control rats. This increase was significantly less than the increase that occurred after 6 months of treatment. Nine months of HAL-induced hyperprolactinemia followed by implantation of PRL-producing MMQ cells, which resulted in very high levels of PRL, did not increase TH activity in the stalk-median eminence. These results demonstrate that hyperprolactinemia over a prolonged period reduces the responsiveness of TIDA neurons, and these effects vary depending on the duration and intensity of hyperprolactinemia.
催乳素（PRL）的分泌受结节漏斗多巴胺能（TIDA）系统的抑制性调节。研究表明，PRL水平的短期升高会增加TIDA神经元的活性，然而，TIDA神经元对血清PRL水平长期升高的反应性存在争议。本研究的目的是探讨血清PRL长期升高对TIDA神经元活性的影响。将2 - 3月龄的雌性Sprague-Dawley大鼠去卵巢，并皮下植入氟哌啶醇（HAL），一种多巴胺受体拮抗剂，持续6或9个月以产生高催乳素血症。去卵巢、假植入的大鼠用作对照。其他完整大鼠组植入HAL或假植入9个月，然后植入分泌PRL的MMQ细胞6周以进一步提高循环PRL水平。通过测量正中隆起处酪氨酸羟化酶（TH）的活性来检测TIDA神经元的活性，并将其与血清PRL水平的变化相关联。治疗6个月后，HAL处理组大鼠的TH活性比对照组高130%。治疗9个月后，HAL处理组大鼠的TH活性比对照组高81%。这种增加明显小于治疗6个月后的增加。9个月的HAL诱导的高催乳素血症后再植入分泌PRL的MMQ细胞，导致PRL水平非常高，但并未增加正中隆起处的TH活性。这些结果表明，长期高催乳素血症会降低TIDA神经元的反应性，且这些影响因高催乳素血症的持续时间和强度而异。
