Extrahypothalamic distribution of CRF-like immunoreactivity in the rat brain

CRF-like immunoreactivity was measured by radioimmunoassay in the brains of normal adult rats and found to be widely distributed in extrahypothalamic areas (e.g., thalamus, amygdala, hippocampus, frontal cerbral cortex, striatum, midbrain, pons-medulla and cerebellum) at levels approximately 10% of the hypothalamus. Sephadex G-50 gel filtration reveals that CRF-like immunoreactivity in the hypothalamus coelutes with synthetic ovine CRF and is also present in the void volume. However, in the extrahypothalamic areas of the rat brain, only CRF-like immunoreactivity that coelutes with synthetic ovine CRF was detected. High performance liquid chromatography revealed equal amounts of immunoreactivity coeluting with CRF and methionine sulfoxide CRF in hypothalamic extracts.     

Corticotropin releasing factor (CRF)-like immunoreactivity in the hypothalamus and posterior pituitary of the goat, bovine, rat, monkey and human

Goat hypothalamic extract prepared by HCl extraction and chromatographed on a Sephadex G-50 column showed two immunoreactive CRF peaks. Most of the immunoreactivity coeluted with synthetic ovine CRF, and a small peak eluted near the void volume. Bovine, monkey, rat and human hypothalamic extracts prepared by acid-acetone or acid-methanol extraction showed three immunoreactive peaks. Most of the immunoreactivity coeluted with ovine CRF, and other smaller peaks eluted near the void volume and slightly before arginine vasopressin. Goat hypothalamic extract showed the highest cross-reactivity with anti-ovine CRF serum, followed by bovine hypothalamic extract. Less cross-reactivity was found in human, rat and monkey hypothalamic extracts. CRF immunoreactivity in goat hypothalamic extract coeluted with ovine CRF on reversed phase high performance liquid chromatography (HPLC) and main CRF immunoreactivity in human and rat hypothalamic extracts eluted slightly later than ovine CRF. These results suggest that there is a heterogeneity among the CRF molecules in these species and that goat CRF may be more similar to that of sheep CRF and the amino acid sequence or molecular weight of other animals CRF may be different from that of sheep CRF. The monkey posterior pituitary and rat neurointermediate lobe showed similar elution patterns of CRF immunoreactivity to their hypothalamic extracts on Sephadex gel filtration and HPLC. These results indicate that the posterior pituitary contains a similar CRF to hypothalamic CRF.     

Brain corticotropin-releasing factor (CRF) and catecholamine responses in acutely stressed rats

Ether-laparotomy stress produced a rapid increase in rat hypothalamic CRF concentration, followed by a rapid reduction and subsequent increase. Cold-restraint stress significantly reduced hypothalamic CRF concentration at 15 min after stress onset. Serum ACTH and corticosterone levels were significantly elevated at 15 min after the onset of both stresses. The CRF responses in the medulla oblongata were not similar to the hypothalamic CRF responses. Norepinephrine concentration in the hypothalamus was reduced, whereas dopamine concentration in the hypothalamus and medulla oblongata was significantly increased. Epinephrine concentrations in these tissues did not show any significant change throughout the stress period. The observations lead to the following conclusions: hypothalamic CRF plays a major role in stimulating ACTH secretion under acute stress; the reduction in hypothalamic CRF is due to an excess release in the early phase of acute stress; hypothalamic CRF and medulla oblongata CRF are controlled by different mechanisms; norepinephrine in the hypothalamus may not be involved in stimulating hypothalamic CRF secretion in the early phase of acute stress; and catecholamines are regulated differently in the hypothalamus and medulla oblongata.     

Effect of morphine on hypothalamic corticotropin-releasing factor (CRF) and pituitary-adrenocortical activity

The effects of intraperitoneal and intra-third ventricular administration of morphine on the hypothalamic corticotropin-releasing factor (CRF) and the pituitary-adrenocortical activity were examined in unanesthetized, freely moving rats. Hypothalamic CRF was measured by rat CRF radioimmunoassay. Intraperitoneal or intra-third ventricular administration of morphine increased blood concentrations of ACTH and corticosterone while intraperitoneal administration tended to increase CRF concentration in the whole hypothalamus including the median eminence and intra-third ventricular administration increased CRF concentration in the hypothalamus excluding the median eminence. However, morphine seemed to inhibit the increase in CRF concentration in the hypothalamus induced by the ether-laparotomy stress. The main site of morphine action on the hypothalamo-pituitary-adrenocortical system seemed to be in the hypothalamic area.     

Reduction in brain immunoreactive corticotropin-releasing factor (CRF) in spontaneously hypertensive rats

The brain CRF concentration of spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) was examined by rat CRF radioimmunoassay. Anti-CRF serum was developed by immunizing rabbits with synthetic rat CRF. Synthetic rat CRF was also used as tracer and standard. The displacement of 125I-rat CRF by serially diluted extracts of male Wistar rats hypothalamus, thalamus, midbrain, pons, medulla oblongata, cerebral cortex, cerebellum and neurointermediate lobe was parallel to the displacement of synthetic rat CRF. In both WKY and SHR the highest levels of CRF immunoreactivity were shown by the hypothalamus and neuro-intermediate lobe, and considerable CRF immunoreactivity was also detected in other brain regions. The CRF immunoreactivity in the hypothalamus, neurointermediate lobe, midbrain, medulla oblongata and cerebral cortex was significantly reduced in SHR and it may suggest that CRF abnormality may be implicated in the reported abnormalities in the pituitary-adrenal axis, autonomic response and behavior of SHR.     

Distribution of corticotropin releasing factor-like immunoreactivity in the rat brain by immunohistochemistry and radioimmunoassay: comparison and characterization of ovine and rat/human CRF antisera

The distribution of corticotropin releasing factor (CRF)-like immunoreactivity in the rat brain has been demonstrated by immunohistochemistry and radioimmunoassay using 4 different antisera. Two antisera were directed against synthetic ovine CRF, two antisera were directed against synthetic rat/human CRF. Immunohistochemistry revealed that there are discrete regions where CRF immunoreactive cell bodies are seen with all 4 antisera (e.g., the paraventricular nucleus, the dorsolateral tegmental nucleus) whereas there are cells observed only with one rat CRF antiserum (e.g., in the cortex) or terminal fields observed only with ovine CRF antisera (e.g., the spinal trigeminal tract, the substantia gelatinosa, the spinal cord). Radioimmunoassay showed different cross reactivity of the antisera with synthetic ovine or rat/human CRF and sauvagine, however, there was no cross reactivity with a variety of other peptides. Tissue values of CRF obtained by RIA of micropunched brain nuclei with the 4 antisera were frequently dissimilar suggesting that different antisera recognize different substances. High performance liquid chromatography and radioimmunoassay of brain tissue samples, revealed that there is more than one form of CRF-like immunoreactivity present. There is indirect evidence that there exists at least one peptide in the rat brain, prominent in the medulla and the spinal cord, which cross reacts with antisera directed to ovine CRF only.     

Corticotropin Releasing Factor (CRF): Immunocytochemical localization and Radioimmunoassay (RIA)

Recent isolation, structural identification, and synthesis of ovine CRF has made possible the generation of specific antibodies against this hypothalamic peptide. Two fragments of the amino acid sequence corresponding to ovine CRF (CRF 37-41 and CRF 22-41), as well as the full sequence of 41 residues (CRF 1-41), synthesized in our laboratories by solid-phase methods, were coupled to bovine serum albumin (BSA) with glutaraldehyde. New Zealand white rabbits were immunized with the emulsified mixtures of peptide-BSA conjugates and Freund's adjuvant as immunogens. The specificity of the generated antibodies was studied by agar-gel diffusion, absorption tests in the immunohistochemical system, and with the aid of displacement curves in RIA. ¹²⁵I-Tyr(35)-CRF 36-41 and ¹²⁵I-Tyr(0)-CRF 1-41 were used as radioligands in the RIA. The minimum detectable dose was 20 pg. The linearity observed in RIA for immunoreactive CRF in extracts of rat hypothalami, together with the immunocytochemical findings in the rat brain, indicate the presence of substance(s) immunologically indistinguishable from CRF. Immunohistochemistry with the peroxidase-antiperoxidase (PAP) technique detected the following CRF-immunoreactive structures in vibratome sections of hypothalami of colchicine-treated rats: CRF-containing cell bodies were observed mainly in smaller neurons of the paraventricular nucleus. CRF-positive nerve fibers and/or terminals were present in the external zone of the median eminence, with some immunoreactive CRF also present in the internal zone. The CRF-positive terminals were localized in the central regions of the median eminence. These morphological data reinforce the view that this polypeptide plays a physiological role in the control of ACTH release.     

Stimulatory effect of acetylcholine on immunoreactive corticotropin-releasing factor release from the rat hypothalamus in vitro

Effects of acetylcholine (Ach) and gamma-aminobutyric acid (GABA) on immunoreactive corticotropin-releasing factor (CRF) release from the rat hypothalamus were examined using a rat hypothalamic perifusion system and a rat CRF RIA in vitro. Ach stimulated CRF release in a dose-dependent manner (1 pM-1 nM). One nM Ach-induced CRF release was inhibited by atropine in a dose-dependent manner (1-100 nM), but was inhibited by only a high concentration (100 nM) of hexamethonium. In addition, such Ach-induced CRF release was inhibited by norepinephrine. GABA did not influence basal CRF release. These results suggest that Ach stimulates CRF release mainly through muscarinic receptors at least under our conditions.     

Possible role of CRF peptides in burn-induced hypermetabolism

Hypermetabolism and anorexia are significant problems associated with major burn trauma. Recent studies have shown that hypothalamic corticotropin releasing factor (CRF) elevates metabolic rate, while neuropeptide Y (NPY) reduces it. CRF also elicits anorexia, while NPY stimulates feeding. We hypothesized that elevation of CRF and decrease of NPY may be mediators of these negative effects of burn trauma. Therefore, we assessed concentrations of CRF and NPY in hypothalamus of burned rats one, three, and twenty-one days after a 30% body surface area, full-thickness, open flame burn. In addition we determined whether a biochemical lesion of CRF receptors using 3rd ventricle injections of a saporin-CRF conjugated peptide would decrease resting energy expenditure (REE). We found a three-day period of anorexia, with REE significantly increasing three days after the burn trauma. Concentrations of NPY were increased in the PVN-containing dorsomedial region of the hypothalamus 1 and 3 days after burn trauma, but were increased further in the day 1 pair-fed rats suggesting this change was a consequence of the anorexia. Levels of CRF were decreased in the ventromedial region of the hypothalamus in day 1 and day 3 burned and PF rats. Treatment with the saporin-CRF conjugate normalized REE and reduced CRF receptor-2 density in the hypothalamus of burned rats, and blocked CRF-induced hypermetabolism in sham-burned rats. Although these results suggest a role of CRF receptors in mediating burn-induced hypermetabolism, CRF itself may not be the principle ligand, as suggested by the significant elevation of hypothalamic urocortin 15 days after burn injury.     

Expression and posttranslational processing of preprodynorphin complementary DNA in the mouse anterior pituitary cell line AtT-20

A recombinant plasmid containing the rat prodynorphin cDNA was introduced into the mouse anterior pituitary corticotroph cell line AtT-20. These cells normally express and posttranslationally process proopiomelanocortin, but not prodynorphin. Stable transformants were isolated and analyzed for the expression and processing of prodynorphin. The stably transformed AtT-20 cells that expressed a 1.3-kilobase prodynorphin mRNA also expressed prodynorphin protein and processed it to dynorphin peptides. The peptides included leucine-enkephalin, beta-neoendorphin, dynorphin-A8, and dynorphin-B, as identified by gel filtration and reverse phase HPLC followed by RIA using peptide-specific antisera. These results demonstrate that AtT-20 cells efficiently and accurately process prodynorphin at both dibasic sites and monobasic cleavage sites, indicating that the AtT-20 cells contain enzymes capable of cleaving the precursor not only at dibasic residues but also at monobasic residues. The release of prodynorphin-derived peptides paralleled secretion of endogenous proopiomelanocortin-derived peptides when stimulated by CRF, a natural secretagogue for ACTH.     

Processing of somatostatin precursors: evidence for enzymatic cleavage by hypothalamic extract

The action of enzymes extracted from rat hypothalamus on the previously characterized high molecular weight forms of hypothalamic somatostatin-like immunoreactivity (4 K SLI and 25 K SLI) has been investigated in vitro in order to further define the role of these molecules as possible precursors for tetradecapeptide somatostatin (SRIF). Studies of the degradation of endogenous SLI and of synthetic SRIF by hypothalamic enzymes showed that the time course of breakdown of endogenous SLI is markedly slower than that of synthetic SRIF due to the relative stability of 25 K SLI as well as the generation of at least two new immunoreactive molecules. Incubation of purified 25 K SLI with SLI-free hypothalamic extract showed after 10 to 30 min newly formed immunoreactive material of an intermediate size between 25 K SLI and 4 K SLI and after 60 min the emergence of material coeluting with SRIF. These data show that the hypothalamus contains the enzymes necessary for degrading endogenous SLI and for processing the 25 K SLI molecule to SRIF providing further evidence that 25 K SLI might be a biosynthetic precursor for SRIF.     

Estrogen and androgen influence hypothalamic AVP and CRF concentrations in fetal and adult sheep

The present study tested the hypothesis that action of sex steroids on the hypothalamus-pituitary-adrenal (HPA) axis is measurable in the hypothalamus. Late-gestation fetal sheep were treated (5 mg/21 days) with either estradiol, androstenedione, or tamoxifen and compared to age-matched control fetuses. Tamoxifen significantly increased hypothalamic corticotropin releasing factor (CRF) and arginine vasopressin (AVP) concentrations, and androstenedione significantly decreased hypothalamic CRF concentration. Adult sheep were treated with estrone (10 mg/21 days), and responded with significant increases in hypothalamic AVP concentration, but not in immunoreactive ACTH concentration or processing within the pituitary. The results demonstrate that the effect of estrogen on the HPA axis is measurable in the hypothalamus, and is therefore not primarily at the anterior pituitary.     

Regulation of hypoxia-induced release of corticotropin-releasing factor in the rat hypothalamus by norepinephrine

Corticotropin-releasing factor (CRF) peptide release was activated by hypoxia in the rat hypothalamus. The mechanisms, however, of the hypoxia-induced CRF release remains unclear. In this study, we demonstrated that the norepinephrine (NE) and its receptors in the paraventricular nucleus (PVN) mediated the CRF release in a simulated altitude hypoxia. When rats were exposed to 5 or 7 km altitude of hypoxia for a short or long term: (1) NE levels in the PVN and the CeA, using the HPLC analysis, were intensity and time course dependently increased, but the increase in the PVN were potential than in the CeA. Restraint-induced NE increase was much higher in both the PVN and the CeA, compared with hypoxia-induced response. (2) Hypoxia and restraint significantly enhanced CRF release in the ME and the PVN but not in the CeA, through RIA assay, which result in stimulating corticosterone secretion. (3) Hypoxia-induced CRF release was reversed by an injection of prazosin (i.c.v.), an alpha-1 adrenoceptor antagonist, while administration of yohimbine (i.c.v.), an alpha-2 receptor antagonist, facilitated further CRF release. These data suggested that hypoxia induced NE activation centrally, via alpha-1 and -2 receptors, leading to improving hypothalamic CRF release, which in turn stimulated pituitary and adrenal cortex. Restraint presented much potential action on NE activation than hypoxia.     

The kallikrein-kinin system in the rat hypothalamus

Summary High molecular weight kininogen (HKg) and T kininogen (TKg) were detected and localized by immunocytochemistry in adult rat hypothalamus. In addition, kininogens were measured by their direct radioimmunoassay (RIA) or by indirect estimation of kinins released after trypsin hydrolysis and high pressure liquid chromatography (HPLC) separation of bradykinin (BK) and T kinin. A specific HKg immunoreactivity demonstrated with antibodies directed against the light chain (LC) of HKg was colocated with SRIF in neurons of hypothalamic periventricular area (PVA) projecting to external zone (ZE) of median eminence (ME). Heavy chain (HC) immunoreactivity which could be related to HKg or to low molecular weight kininogen (LKg) was detected in some other systems: i) parvocellular neurons of suprachiasmatic (SCN) and arcuate nuclei containing SRIF, ii) magnocellular neurons (mostly oxytocinergic) of paraventricular (PVN) and supraoptic (SON) nuclei, iii) neurons of dorsomedian and lateral hypothalamic areas. TKg immunostaining was restricted to magnocellular neurons of PVN, SON, accessory nuclei (mostly vasopressinergic) and to parvocellular neurons of SCN (vasopressinergic). TKg projections are directed towards the internal zone (ZI) of ME, but very few immunoreactive terminals are detectable in neurohypophysis. TKg staining parallels with vasopressin during water deprivation, and is undetectable in homozygous Brattleboro rats. In some magnocellular neurons, TKg and HC (related to HKg or LKg) are coexpressed. TKg, was also detected in hypothalamus and cerebellum extracts by direct RIA, and BK and T kinin were identified after trypsin hydrolysis. HKg and LKg can act as precursor of BK which can play a physiological role as releasing factor, neuromodulator — neurotransmitter, — or modulator of local microcirculation in hypothalamus. The three kininogens are also potent thiolprotease inhibitors which could modulate both the maturation processes of peptidic hormones and their inactivation and catabolism.     

CRF immunoreactive peptides in the human hypophysis: a cautionary note

By monitoring with a non competitive enzyme linked immunosorbent assay (ELISA), corticotropin releasing factor (CRF)-like immunoreactive material was isolated from the human hypophysis. After acid extraction of peptides from frozen human hypophyses, the purification was achieved by affinity chromatography using purified anti-ovine-CRF IgG bound to a solid phase and then by two HPLC steps using an alkylsilane-bonded large pore size silica. Two CRF-like peptides were purified: discrete immunoreactive peaks coinciding with an optical density peak at 215 nm. Although these peptides were recognized by ELISA, they were not recognized in an RIA using the same anti-ovine-CRF serum and ovine CRF-41 as tracer. Neither of these CRF-immunoreactive peptides had any effect on either the spontaneous or stimulated ACTH release in the perfused isolated anterior pituitary cell bioassay.     

Physiological changes in rat hypothalamic CRF: Circadian,stress and steroid suppression

Hypothalamic CRF-like immunoreactivity was measured in the a.m. and p.m., after systemic dexamethasone administration or after either stress in adult male rats. Measurement of plasma corticosterone levels revealed the expected circadian rhythmicity, suppression after dexamethasone administration and increase after ether stress. The hypothalamic content of CRF-like immunoreactivity was significantly decreased in the p.m. and after dexamethasone administration. However, no change in hypothalamic CRF-like immunoreactivity was observed after ether stress. The results are consistent with an increased release in the p.m. and decreased synthesis of hypothalamic CRF after systemic dexamethasone administration. The observation that there is no change in content of hypothalamic CRF-like immunoreactivity after ether stress could be due to the fact that the animals were stressed by handling. The results show that this immunoreactivity present in the hypothalamus is altered by changes in the hypothalamic-pituitaryadrenal axis and thus suggest that this peptide is a physiologically significant CRF in the rat.     

The kallikrein-kinin system in the rat hypothalamus. Immunohistochemical localization of high molecular weight kininogen and T kininogen in different neuronal systems

High molecular weight kininogen (HKg) and T kininogen (TKg) were detected and localized by immunocytochemistry in adult rat hypothalamus. In addition, kininogens were measured by their direct radioimmunoassay (RIA) or by indirect estimation of kinins released after trypsin hydrolysis and high pressure liquid chromatography (HPLC) separation of bradykinin (BK) and T kinin. A specific HKg immunoreactivity demonstrated with antibodies directed against the light chain (LC) of HKg was colocated with SRIF in neurons of hypothalamic periventricular area (PVA) projecting to external zone (ZE) of median eminence (ME). Heavy chain (HC) immunoreactivity which could be related to HKg or to low molecular weight kininogen (LKg) was detected in some other systems: i) parvocellular neurons of suprachiasmatic (SCN) and arcuate nuclei containing SRIF, ii) magnocellular neurons (mostly oxytocinergic) of paraventricular (PVN) and supraoptic (SON) nuclei, iii) neurons of dorsomedian and lateral hypothalamic areas. TKg immunostaining was restricted to magnocellular neurons of PVN, SON, accessory nuclei (mostly vasopressinergic) and to parvocellular neurons of SCN (vasopressinergic). TKg projections are directed towards the internal zone (ZI) of ME, but very few immunoreactive terminals are detectable in neurohypophysis. TKg staining parallels with vasopressin during water deprivation, and is undetectable in homozygous Brattleboro rats. In some magnocellular neurons, TKg and HC (related to HKg or LKg) are coexpressed. TKg, was also detected in hypothalamus and cerebellum extracts by direct RIA, and BK and T kinin were identified after trypsin hydrolysis. HKg and LKg can act as precursor of BK which can play a physiological role as releasing factor, neuromodulator--neurotransmitter,--or modulator of local microcirculation in hypothalamus. The three kininogens are also potent thiolprotease inhibitors which could modulate both the maturation processes of peptidic hormones and their inactivation and catabolism.     

Comparison of a specific two-site immunoradiometric assay with radioimmunoassay for rat/human CRF-41

We report the development of an immunoradiometric assay (IRMA) for the specific measurement of corticotrophin releasing factor (CRF-41) which uses two antibodies directed to opposite ends of the CRF-41 molecule. In this assay, 125I-labelled affinity purified rabbit anti-(CRF 36-41) immunoglobulin (IgG) and a guinea-pig anti-(CRF 1-20) serum are simultaneously added to 200 microliter volumes of standard or unknown. After 16 h incubation at room temperature, free and CRF-bound guinea-pig antibodies are precipitated using affinity purified sheep anti-(guinea-pig Fc region) IgG coupled to solid phase Dynospheres. Radioactive rabbit anti-(CRF 36-41) is only precipitated in tubes containing CRF-41, since the peptide acts as a link between the 125I-labelled rabbit IgG and the unlabelled guinea-pig CRF-specific antibodies. Precipitated counts are directly proportional to the concentration of CRF-41 in the sample. This CRF IRMA is compared with two radioimmunoassays (RIA) using the N- and C-terminal CRF antisera employed in the IRMA and found to be more sensitive, specific and rapid to perform. The CRF-41 content of rat and human hypothalamic extracts is the same whether measured by IRMA or conventional RIA. Sephadex G50 chromatography of rat hypothalamic extracts reveals two peaks, detected equally by IRMA and RIA, with a main peak in the elution position of synthetic CRF-41, and a smaller void peak. This is the case whether the hypothalamic extracts are prepared from adrenalectomised or sham-operated rats, non-stressed or subjected to ether stress. Re-chromatography of pooled void peaks under dissociating conditions gives the elution profile of synthetic CRF-41, indicating that the large molecular weight 'CRF-41' peak is not a CRF-41 precursor, but is due to CRF-41 associating non-covalently with large molecular weight proteins.     

Corticotropin-releasing activity in the rat gastric antrum

Rat gastric antrum, duodenum, pancreas, and spleen were extracted in acetic acid, treated with acetone, and purified on a C-18 cartridge. These extracts, in a dose equivalent to one respective organ, were examined for CRF bioactivity in vitro using rat half pituitaries, with gastric antrum extract showing a significant CRF activity. The antrum extract showed a dose-related CRF activity in vitro using rat pituitary cell culture, and the dose-response curve appeared to be parallel with that of synthetic rat hypothalamic CRF. Subsequent ion-exchange chromatography on a SP-Sephadex column showed that antrum CRF coeluted with basic materials (SP-III fraction), while rat hypothalamic CRF coeluted with weakly basic materials (SP-II fraction). The SP-III fraction was further purified by gel filtration on Sephadex G-50. CRF activity was eluted in two areas: large mol wt fraction (10,000-15,000) and small mol wt fraction (1500-2000). Hypothalamic CRF was eluted between them. The CRF activities of the two fractions were completely abolished by trypsin digestion, suggesting a peptide nature. The large molecular weight fraction exhibited a steeper dose-response curve than the hypothalamic CRF in vitro using cell culture, and the response to a dose equivalent to two antra exceeded the maximum response exhibited by the hypothalamic CRF. However, the fraction failed to increase serum corticosterone when injected in pharmacologically blocked rats. On the other hand, the small molecular weight fraction showed a lesser CRF activity and a similar dose-response curve to that of the hypothalamic CRF as tested in vitro. This fraction significantly stimulated corticosterone secretion in vivo as well. The small molecular weight activity did not appear to be due to other peptides or amines which have been reported as causing ACTH release. Although the physiological roles of the small molecular weight antrum CRF are unknown, it is possible that this CRF plays a role during stress as a tissue CRF.     

新生大鼠下丘脑CRF和AVP神经元对急性低氧的应答

目的:观察肾上腺摘除新生大鼠下丘脑促肾上腺皮质激素释放激素(CRF)和精氨酸加压素(AVP)神经元对急性低氧的应答.方法:在低压氧舱中模拟高海拔低氧,用放免法测定AVP和CRP含量.结果:新生大鼠暴露于急性低氧环境下(模拟5 000 m和7 000 m海拔高度,24 h),其下丘脑CRP在3 d和7 d龄大鼠中无明显变化,但14d、21 d和28 d时低于对照;下丘脑AVP在3 d大鼠中亦无变化,但14 d时低于对照,7 d、21 d及28 d时高于对照.两者对低氧的应答模式随日龄而变化.摘除肾上腺后,14 d、21 d及28 d大鼠下丘脑CRF和AVP含量均显著低于同龄完整大鼠,此时暴露于急性低氧环境下,CRF和AVP无进一步的变化.结论:摘除肾上腺抑制下丘脑CRF和AVP的发育,影响它们对低氧应激的正常应答.