Samson W K, Aguila M C, Bianchi R
Department of Physiology, University of Texas Health Science Center, Dallas 75235-9040.
Endocrinology. 1988 Apr;122(4):1573-82. doi: 10.1210/endo-122-4-1573.
The presence of atrial natriuretic factor (ANF) immunoreactivity and receptors for ANF in the median eminence, hypothalamus, and anterior pituitary gland suggests a role for the peptide in the hypothalamic control of anterior pituitary function. In conscious ovariectomized female rats, transient elevation of plasma levels of ANF by volume loading, a stimulus known to release endogenous ANF from the heart, or by bolus iv injection of 0.1, 1.0, or 10 micrograms synthetic ANF failed to result in altered circulating levels of LH or GH. Constant iv infusion of ANF for 30 min, such that 2- to 3-fold elevations in plasma ANF were detected by RIA resulted, however, in significant inhibition of LH release in ovariectomized female rats (0.05 and 0.1 micrograms ANF/kg.min) and orchidectomized male rats (0.1 microgram ANF/kg.min). It was unlikely that this effect was exerted at the level of the anterior pituitary, since ANF failed to alter basal or LHRH-stimulated LH release from cultured anterior pituitary cells in vitro and since iv infusion of 0.1 microgram ANF/kg.min failed to alter pituitary responsiveness in vivo to a 10-ng bolus injection of LHRH. Significant inhibition of LH secretion was also observed after third cerebroventricular injection of 1.0 or 2.0 nmol ANF. As with iv infusion, central administration of ANF failed to significantly alter GH secretion. LHRH release from median eminence explants incubated in vitro in the presence of dopamine (60 or 120 microM) was inhibited by 10(-7) M ANF, suggesting a median eminence site of action of the peptide. Finally, an opiate involvement in the mechanism of ANF's action was suggested, since naloxone (0.5 mg, iv, followed by a 60-min infusion of an additional 1 mg) completely blocked the ability of ANF (0.1 or 0.5 microgram/kg.min, infused over the last 30 min of naloxone administration) to inhibit LH release. These data suggest that ANF can act centrally to alter the hypothalamic control of gonadotropin secretion, possibly by interacting with central dopaminergic and peptidergic systems. They further suggest actions of ANF within the brain unrelated to its previously described effects on fluid and electrolyte homeostasis.
心房利钠因子（ANF）免疫反应性及其受体在下丘脑正中隆起、下丘脑和垂体前叶的存在，提示该肽在垂体前叶功能的下丘脑控制中发挥作用。在清醒的去卵巢雌性大鼠中，通过容量负荷（一种已知可从心脏释放内源性ANF的刺激）或静脉推注0.1、1.0或10微克合成ANF使血浆ANF水平短暂升高，未能导致LH或GH的循环水平改变。然而，以每分钟每千克体重静脉持续输注ANF 30分钟，使血浆ANF水平通过放射免疫分析（RIA）检测到升高2至3倍，结果导致去卵巢雌性大鼠（0.05和0.1微克ANF/千克·分钟）和去势雄性大鼠（0.1微克ANF/千克·分钟）的LH释放受到显著抑制。这种作用不太可能是在垂体前叶水平发挥的，因为ANF未能改变体外培养的垂体前叶细胞基础或LHRH刺激的LH释放，并且以每分钟每千克体重静脉输注0.1微克ANF未能改变体内垂体对10纳克LHRH推注的反应性。在第三脑室注射1.0或2.0纳摩尔ANF后，也观察到LH分泌受到显著抑制。与静脉输注一样，ANF的中枢给药未能显著改变GH分泌。在多巴胺（60或120微摩尔）存在下体外培养来自正中隆起的外植体，10⁻⁷ M的ANF可抑制LHRH释放，提示该肽的作用位点在正中隆起。最后，提示阿片类物质参与了ANF的作用机制，因为纳洛酮（0.5毫克，静脉注射，随后在60分钟内额外输注1毫克）完全阻断了ANF（0.1或0.5微克/千克·分钟，在纳洛酮给药的最后30分钟内输注）抑制LH释放的能力。这些数据表明，ANF可通过与中枢多巴胺能和肽能系统相互作用，在中枢发挥作用以改变下丘脑对促性腺激素分泌的控制。它们还提示ANF在脑内的作用与其先前描述的对液体和电解质稳态的影响无关。
