Brown E R, Harlan R E, Krause J E
Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110.
Endocrinology. 1990 Jan;126(1):330-40. doi: 10.1210/endo-126-1-330.
Substance P-like immunoreactivity (SP-LI) is present in the rat anterior pituitary (AP) and in hypothalamic neurons that may be involved in the control of AP secretion and/or reproductive function. The presence of multiple SP-encoding mRNAs and tachykinin peptides and their regulation by steroid hormones were examined in APs and hypothalami from normal, gonadectomized, and steroid-treated male and female rats. SP-encoding mRNAs were identified by nuclease protection assays of RNA, and tachykinin peptides were identified by combined HPLC-RIA of tissue extracts, beta- and gamma-preprotachykinin (PPT) mRNAs and SP, neurokinin A, and neuropeptide gamma peptides were identified in the AP. The alpha-, beta-, and gamma-PPT mRNAs and SP, neurokinin A, neuropeptide gamma, neuropeptide K, and neurokinin B peptides were present in hypothalamic tissue. Previous studies have established that in the AP, SP is differentially regulated by gonadal steroids; estrogen decreases and androgen increases AP SP. Steroid effects were further analyzed in experiments using RIAs to measure SP levels in the AP and median eminence (ME) of steroid- and oil-treated gonadectomized rats. To assess whether steroids alter steady state PPT mRNA levels and presumably SP synthesis in these tissues, potential effects on AP and hypothalamic SP-encoding mRNAs were determined. Ovariectomized rats treated for 10 days with estradiol benzoate showed a 50% decrease in AP SP and a 90% decrease in AP beta- and gamma-PPT mRNAs compared to ovariectomized oil-treated controls. Estradiol benzoate replacement had no effect on SP levels in the isolated ME, but did cause a 50% increase in alpha-, beta-, and gamma PPT mRNAs in the hypothalamus. Although there was no significant effect of testosterone propionate on AP SP levels in castrated males, 10 days of testosterone propionate replacement did cause a significant increase in beta- and gamma PPT mRNAs in the AP. No androgen effects were seen on either ME SP or hypothalamic SP-encoding mRNAs. These data demonstrate that estrogen up-regulates SP-encoding mRNAs in the hypothalamus, whereas it down-regulates SP-encoding mRNAs in the pituitary. These results implicate SP and other tachykinins derived from the SP gene as steroid-regulated modulators of AP secretion and possibly reproductive function.
P物质样免疫反应性（SP-LI）存在于大鼠垂体前叶（AP）以及下丘脑神经元中，这些神经元可能参与对AP分泌和/或生殖功能的控制。研究了正常、去性腺以及经类固醇处理的雄性和雌性大鼠的AP和下丘脑组织中多种编码SP的mRNA、速激肽肽类及其受类固醇激素调控的情况。通过RNA核酸酶保护试验鉴定编码SP的mRNA，通过组织提取物的高效液相色谱-放射免疫分析法（HPLC-RIA）鉴定速激肽肽类，在AP中鉴定出β-和γ-前速激肽原（PPT）mRNA以及SP、神经激肽A和神经肽γ肽类。下丘脑组织中存在α-、β-和γ-PPT mRNA以及SP、神经激肽A、神经肽γ、神经肽K和神经激肽B肽类。先前的研究表明，在AP中，SP受性腺类固醇的差异调节；雌激素降低而雄激素增加AP中的SP。在使用放射免疫分析法测量经类固醇和油处理的去性腺大鼠的AP和正中隆起（ME）中SP水平的实验中，进一步分析了类固醇的作用。为了评估类固醇是否改变这些组织中稳态PPT mRNA水平以及推测SP的合成，确定了对AP和下丘脑编码SP的mRNA的潜在影响。与经油处理的去卵巢对照大鼠相比，用苯甲酸雌二醇处理10天的去卵巢大鼠AP中的SP减少了50%，AP中的β-和γ-PPT mRNA减少了90%。苯甲酸雌二醇替代对分离出的ME中的SP水平没有影响，但确实使下丘脑中α-、β-和γ-PPT mRNA增加了50%。虽然丙酸睾酮对去势雄性大鼠的AP中SP水平没有显著影响，但10天的丙酸睾酮替代确实使AP中的β-和γ-PPT mRNA显著增加。未观察到雄激素对ME中的SP或下丘脑编码SP的mRNA有影响。这些数据表明，雌激素上调下丘脑中编码SP的mRNA，而下调垂体中编码SP的mRNA。这些结果表明，SP以及源自SP基因的其他速激肽是AP分泌以及可能的生殖功能的类固醇调节调节剂。
