Orphanin FQ/nociceptin is a physiological regulator of prolactin secretion in female rats
Orphanin FQ/nociceptin is a physiological regulator of prolactin secretion in female rats
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DOI：
10.1210/en.2006-0707
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发表时间：
2006-11-01
期刊：
影响因子：
4.8
通讯作者：
Callahan, Phyllis
中科院分区：
文献类型：
--
作者：
Chesterfield, Matthew;Janik, James;Callahan, Phyllis
孤啡肽/伤害素(OFQ/N)是新近发现的一种内源性阿片肽，可刺激雄性和雌性大鼠催乳素的分泌。然而，OFQ/N不能通过µ-阿片受体亚型、β-阿片受体亚型或kappa-阿片受体亚型产生这种刺激效应。Q/N在生理条件下对催乳素的调节作用及其作用机制尚不清楚。本研究的目的是确定催乳素对OFQ/N的分泌反应的生理学意义和药理学特异性。此外，还研究了结节漏斗多巴胺能神经元(TIDA)在调节这种反应中的作用。阿片受体样受体1(ORL-1)受体可被OFQ/N拮抗剂B(Comp B)阻断，或ORL-1受体反义寡核苷酸阻断受体合成。测定了哺乳期雌性大鼠对OFQ/N给药后的催乳素分泌反应。此外，还测定了补体B预处理后哺乳诱导的催乳素反应。对发情雌性大鼠的TIDA神经元活动进行量化，以确定OFQ/N是否通过抑制TIDA神经元来刺激催乳素的释放。OFQ/N显著抑制催乳素分泌反应前1min的TIDA神经元。COMP B和反义预处理均可阻断OFQ/N对催乳素释放的刺激作用，且COMP B可阻断哺乳诱导的催乳素反应。这些研究表明，OFQ/N是一种对雌性大鼠催乳素分泌的有效刺激，它通过快速和短暂地抑制TIDA神经元的活动来介导这一作用。此外，OFQ/N在哺乳期催乳素分泌的调节中起着重要的生理作用，它通过作用于ORL-1受体亚型来调节其作用。
Orphanin FQ/nociceptin (OFQ/N), the most recently identified endogenous opioid peptide, stimulates prolactin secretion in both male and female rats. OFQ/N, however, did not elicit this stimulatory effect through the mu-, delta-, or kappa-opiate receptor subtype. The role OFQ/N plays in prolactin regulation under physiological conditions and its mechanism of action are not known. The purpose of these studies was to determine the physiological significance and pharmacological specificity of the prolactin secretory response to OFQ/N. In addition, the role of the tuberoinfundibular dopaminergic (TIDA) neurons in mediating this response was examined. Opioid receptor-like-1 (ORL-1) receptors were blocked by pretreatment with compound B (Comp B), a purported OFQ/N antagonist, or receptor synthesis was disrupted by pretreatment with ORL-1 receptor antisense oligonucleotides. The prolactin secretory response to OFQ/N administration in diestrous females was measured. Furthermore, the suckling-induced prolactin response was also determined after Comp B pretreatment. TIDA neuronal activity was quantified in diestrous female rats to determine whether OFQ/N stimulates prolactin release by inhibiting TIDA neurons. OFQ/N significantly inhibited the TIDA neurons by 1 min, preceding the prolactin secretory response. Both Comp B and antisense pretreatment blocked the stimulatory effects of OFQ/N on prolactin release, and Comp B abolished the suckling-induced prolactin response. These studies indicate that OFQ/N is a potent stimulus for prolactin secretion in female rats and that it mediates this effect by rapid and transient inhibition of TIDA neuronal activity. Furthermore, OFQ/N plays a physiologically significant role in the regulation of prolactin secretion during lactation, and it mediates its effects via actions at the ORL-1 receptor subtype.