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排序方式: 共有778条查询结果,搜索用时 15 毫秒
91.
R J Urban V Padmanabhan I Beitins J D Veldhuis 《The Journal of clinical endocrinology and metabolism》1991,73(4):818-823
We measured the equilibrium MCR of purified human FSH via continuous infusion and its half-life by bolus injection in gonadotropin-deficient men. Serum FSH concentrations were determined by RIA, immunoradiometric assay, and an in vitro FSH bioassay (rat Sertoli cell). At steady state, the MCR of FSH averaged 5.4 +/- 0.4 mL/min.m2, which was not statistically different in the three assays at the three different infusion rates. The half-life of FSH after bolus injection averaged 274 +/- 45 min (4.6 +/- 0.75 h) when analyzed as a single exponential, and 1.8 and 10 h for biexponential kinetics. The distribution volume of FSH was 3.1 L (immunoradiometric assay) and 2.1 L (bioassay). In summary, the MCR of human FSH is invariant across a range of physiological gonadotropin concentrations and quantitatively similar in three different immunological/biological assays. These results support the hypothesis that removal of circulating FSH molecules proceeds in parallel for immunoreactive and biologically active glycoprotein hormone. 相似文献
92.
M L Hartman J D Veldhuis M L Johnson M M Lee K G Alberti E Samojlik M O Thorner 《The Journal of clinical endocrinology and metabolism》1992,74(4):757-765
Serum GH concentrations are increased in fasted or malnourished human subjects. We investigated the dynamic mechanisms underlying this phenomenon in nine normal men by analyzing serum GH concentrations measured in blood obtained at 5-min intervals over 24 h on a control (fed) day and on the second day of a fast with a multiple-parameter deconvolution method to simultaneously resolve endogenous GH secretory and clearance rates. Two days of fasting induced a 5-fold increase in the 24-h endogenous GH production rate [78 +/- 12 vs. 371 +/- 57 micrograms/Lv (Lv, liter of distribution volume) or 0.24 +/- 0.038 vs. 1.1 +/- 0.16 mg/m2 (assuming a distribution volume of 7.9% body weight), P = 0.0001]. This enhanced GH production rate was accounted for by 2-fold increases in the number of GH secretory bursts per 24 h (14 +/- 2.3 vs. 32 +/- 2.4, P = 0.0006) and the mass of GH secreted per burst (6.3 +/- 1.2 vs. 11 +/- 1.6 micrograms/Lv, P = 0.002). The latter was a result of increased secretory-event amplitudes (maximal rates of GH release attained within a burst) with unchanged secretory burst durations. GH was secreted in complex volleys composed of multiple discrete secretory bursts. These secretory volleys were separated by shorter intervals of secretory quiescence in the fasted than fed state (respectively, 88 +/- 4.2 vs. 143 +/- 14 min, P = 0.0001). Similarly, within volleys of GH release, constituent individual secretory bursts occurred more frequently during the fast [every 33 +/- 0.64 (fasted) vs. every 44 +/- 2.0 min (fed), P = 0.0001]. The t1/2 of endogenous GH was not significantly altered by fasting [18 +/- 2.2 (fasted) vs. 20 +/- 1.5 min (fed), P = 0.47]. Serum insulin-like growth factor I concentrations were unchanged after 56 h of fasting. In conclusion, the present data suggest that starvation-induced enhancement of GH secretion is mediated by an increased frequency of GHRH release, and longer and more pronounced periods of somatostatin withdrawal. 相似文献
93.
94.
Somatotropin pulse frequency and basal concentrations are increased in acromegaly and are reduced by successful therapy 总被引:6,自引:0,他引:6
M L Hartman J D Veldhuis M L Vance A C Faria R W Furlanetto M O Thorner 《The Journal of clinical endocrinology and metabolism》1990,70(5):1375-1384
Alterations in pulsatile GH release in 13 acromegalic patients (7 men and 6 women) were studied by measuring serum GH concentrations in blood sampled every 5 min over 24 h. Specific properties of pulsatile GH release were quantitated by Cluster analysis, and Fourier expansion time series analysis was used to resolve fixed periodicities underlying GH secretion. Compared with sex-matched controls, 24-h integrated GH concentrations (IGHC; min.mg/L) were elevated 15-fold in the acromegalic men (40 +/- 27 vs. 2.6 +/- 0.35; P = 0.02) and 10-fold in the acromegalic women (43 +/- 19 vs. 4.1 +/- 0.35; P = 0.01). The increase in integrated GH concentrations was accounted for by an increase in the nonpulsatile fraction [men, 31 +/- 20 vs. 0.65 +/- 0.10 (P = 0.001); women, 35 +/- 14 vs. 1.2 +/- 0.10 (P = 0.0008)]; the pulsatile component was not different from that in normal subjects. Acromegalics had an increased number of pulses per 24 h [men, 17 +/- 1.5 vs. 6.7 +/- 1.4 (P = 0.0001); women, 19 +/- 1.6 vs. 11 +/- 1.0 (P = 0.002)] and increased basal GH concentrations [men, interpulse valley mean, 22 +/- 14 vs. 1.4 +/- 0.30 micrograms/L (P = 0.0006); women, 27 +/- 12 vs. 1.3 +/- 0.20 micrograms/L (P = 0.0001)]. The proportion of the mean GH concentration attributable to 24-h rhythmicity was decreased in the acromegalic patients. Five patients studied during biochemical remission (4 after transsphenoidal surgery and 1 during bromocriptine therapy) had GH profiles that resembled those of normal subjects. Pulsatile GH secretion in acromegaly is characterized by augmented basal GH concentrations, increased GH pulse frequency, and an attenuation of the underlying 24-h rhythm. Such a pattern may be secondary to the intrinsic pathology of adenomatous somatotrophs and/or the effects of altered hypothalamic regulation. 相似文献
95.
C S Mantzoros M Ozata A B Negrao M A Suchard M Ziotopoulou S Caglayan R M Elashoff R J Cogswell P Negro V Liberty M L Wong J Veldhuis I C Ozdemir P W Gold J S Flier J Licinio 《The Journal of clinical endocrinology and metabolism》2001,86(7):3284-3291
Leptin signals the status of energy reserves to the brain. Leptin stimulates biosynthesis of TRH in vitro and influences the activity of the hypothalamic-pituitary-thyroid axis in vivo in rodents. Because blood levels of both leptin and TSH display diurnal variation with a distinct nocturnal rise, we sought to determine whether a relationship exists between fluctuations in circulating leptin and TSH. We measured serum leptin and TSH levels every 7 min for 24 h in five healthy men and found that both leptin and TSH levels are highly organized and pulsatile. A similar pattern of leptin and TSH rhythms was observed, with TSH and leptin levels reaching a nadir in late morning and a peak in the early morning hours. Importantly, cosinor analysis on the absolute leptin and TSH levels revealed a statistically significant fit for a 24-h period and the two hormones showed similar probabilities of rhythm and superimposable peak values. Furthermore, this study shows a strong positive Pearson correlation between the 24-h patterns of variability of leptin and TSH in healthy subjects. Finally, the ultradian fluctuations in leptin levels showed pattern synchrony with those of TSH as determined by cross-correlation analysis, by cross-approximate enthropy and Bayessian analysis applied independently. To further explore whether these associations could reflect an underlying regulation of TSH secretion by leptin, we also studied frequently sampled leptin and TSH levels in four brothers, members of a family with leptin deficiency (one normal homozygote, two heterozygotes, and one leptin-deficient homozygote). Leptin levels of the homozygous leptin-deficient subject are detectable but bioinactive, and the rhythm of his TSH is disorganized. 24-h pattern of leptin and TSH variability in the heterozygous subjects, although significantly correlated, showed a weaker correlation compared with the strong correlation in the normal subjects. These data are consistent with the possibility that leptin may regulate TSH pulsatility and circadian rhythmicity, but interventional studies are needed to definitively prove whether leptin regulates the minute-to-minute oscillations and ultradian rhythm of TSH levels. 相似文献
96.
S M Anderson L Wideman J T Patrie A Weltman C Y Bowers J D Veldhuis 《The Journal of clinical endocrinology and metabolism》2001,86(12):5904-5911
Female gender confers resistance to GH autonegative feedback in the adult rat, thereby suggesting gonadal or estrogenic modulation of autoregulation of the somatotropic axis. Here we test the clinical hypothesis that short-term E2 replacement in ovariprival women reduces GH's repression of spontaneous, GHRH-, and GH-releasing peptide (GHRP)-stimulated GH secretion. To this end, we appraised GH autoinhibition in nine healthy postmenopausal volunteers during a prospective, randomly ordered supplementation with placebo vs. E [1 mg micronized 17 beta-E2 orally twice daily for 6-23 d]. The GH autofeedback paradigm consisted of a 6-min pulsed i.v. infusion of recombinant human GH (10 microg/kg square-wave injection) or saline (control) followed by i.v. bolus GHRH (1 microg/kg), GHRP-2 (1 microg/kg), or saline 2 h later. Blood was sampled every 10 min and serum GH concentrations were measured by chemiluminescence. Poststimulus GH release was quantitated by multiparameter deconvolution analysis using published biexponential kinetics and by the incremental peak serum GH concentration response (maximal poststimulus value minus prepeak nadir). Outcomes were analyzed on the logarithmic scale by mixed-effects ANOVA at a multiple-comparison type I error rate of 0.05. E2 supplementation increased the (mean +/- SEM) serum E2 concentration from 43 +/- 1.8 (control) to 121 +/- 4 pg/ml (E2) (158 +/- 6.6 to 440 +/- 15 pmol/liter; P < 0.001), lowered the 0800 h (preinfusion) serum IGF-I concentration from 127 +/- 7.7 to 73 +/- 3.6 microg/liter (P < 0.01), and amplified spontaneous pulsatile GH production from 7.5 +/- 1.1 to 13 +/- 2.3 microg/liter per 6 h (P = 0.020). In the absence of exogenously imposed GH autofeedback, E2 replacement enhanced the stimulatory effect of GHRP-2 on incremental peak GH release by 1.58-fold [95% confidence interval, 1.2- to 2.1-fold] (P = 0.0034) but did not alter the action of GHRH (0.83-fold [0.62- to 1.1-fold]). In the E2-deficient state, bolus GH infusion significantly inhibited subsequent spontaneous, GHRH-, and GHRP-induced incremental peak GH responses by, respectively, 33% (1-55%; P = 0.044 vs. saline), 79% (68-86%; P < 0.0001), and 54% (32-69%; P = 0.0002). E2 repletion failed to influence GH autofeedback on either spontaneous or GHRH-stimulated incremental peak GH output. In contrast, E2 replenishment augmented the GHRP-2-stimulated incremental peak GH response in the face of GH autoinhibition by 1.7-fold (1.2- to 2.5-fold; P = 0.009). Mechanistically, the latter effect of E2 mirrored its enhancement of GH-repressed/GHRP-2-stimulated GH secretory pulse mass, which rose by 1.5-fold (0.95- to 2.5-fold over placebo; P = 0.078). In summary, the present clinical investigation documents the ability of short-term oral E2 supplementation in postmenopausal women to selectively rescue GHRP-2 (but not spontaneous or GHRH)-stimulated GH secretion from autonegative feedback. The secretagogue specificity of E's relief of GH autoinhibition suggests that this sex steroid may enhance activity of the hypothalamopituitary GHRP-receptor/effector pathway. 相似文献
97.
Bergendahl M Evans WS Pastor C Patel A Iranmanesh A Veldhuis JD 《The Journal of clinical endocrinology and metabolism》1999,84(3):883-894
Short term fasting activates the corticotropic and somatotropic, and suppresses the reproductive, axis in men. Analogous neuroendocrine responses are less well characterized in women. Recently, we identified a negative association between the adipocyte-derived nutritional signaling peptide, leptin, and pulsatile GH secretion in older fed women. In the present study, we investigated the impact of acute nutrient deprivation on pulsatile GH and LH secretion and mean leptin concentrations in eight healthy young women in the sex-steroid replete milieu of the midluteal phase of the normal menstrual cycle. Volunteers underwent 24-h blood sampling during randomly ordered, short term (2.5-day), fasting vs. fed sessions in separate menstrual cycles. Pulsatile GH and LH secretion over 24 h was quantified by deconvolution analysis, nyctohemeral rhythmicity was quantified by cosinor analysis, and the orderliness of the GH or LH release process was quantified by the approximate entropy statistic. By paired statistical analysis, a 2.5-day fast failed to alter mean (pooled) 24-h serum concentrations of LH, progesterone, estradiol, or PRL, but increased cortisol levels more than 1.5-fold (P = 0.0003). Concurrently, mean (pooled) serum leptin concentrations fell by 75% (P = 0.0003), and insulin-like growth factor I (IGF-I; P < 0.05) and insulin decreased significantly (P = 0.0018). In contrast, the daily pulsatile GH secretion rate rose 3-fold (P < 0.001). Amplified daily GH secretion was attributable mechanistically to a 2.3-fold rise in GH secretory burst mass, reflecting an increased GH secretory burst amplitude (P < 0.01). The GH half-life, duration of GH secretory bursts, and GH pulse frequency did not vary during short term fasting. The disorderliness of GH release increased significantly with nutrient restriction (P = 0.005). The mesor and amplitude of the nyctohemeral serum GH concentration rhythm also rose with fasting (P < 0.01), but the timing of maximal serum GH concentrations did not change. Thus, short-term (2.5-day) fasting during the sex steroid-replete midluteal phase of the menstrual cycle in healthy young women profoundly suppresses 24-h serum leptin and insulin (and to a lesser degree, IGF-I) concentrations, augments cortisol release, but fails to alter daily LH, estradiol, or progesterone concentrations. In contrast, the GH axis exhibits strikingly amplified pulsatile secretion, increased nyctohemeral rhythmicity, and marked disorderliness of the release process. We conclude that the somatotropic axis is more evidently vulnerable to short-term nutrient restriction than the reproductive axis in steroidogenically sufficient midluteal phase women. This study invites the question of whether normal (nutritionally replete) GH secretory dynamics can be restored in fasting women by human leptin, insulin, or IGF-I infusions. 相似文献
98.
C. S. van Kessel E. de Boer F. J. W. ten Kate L. A. A. Brosens W. B. Veldhuis M. S. van Leeuwen 《Abdominal imaging》2013,38(3):490-501
Objectives
To assess the range of hepatobiliary enhancement patterns of focal nodular hyperplasia (FNH) after gadoxetic-acid injection, and to correlate these patterns to specific histological features.Materials and methods
FNH lesions, imaged with Gadoxetic-acid-enhanced MRI, with either typical imaging findings on T1, T2 and dynamic-enhanced sequences or histologically proven, were evaluated for hepatobiliary enhancement patterns and categorized as homogeneously hyperintense, inhomogeneously hyperintense, iso-intense, or hypo-intense-with-ring. Available histological specimens of FNHs (surgical resection or histological biopsy), were re-evaluated to correlate histological features with observed enhancement patterns.Results
26 FNHs in 20 patients were included; histology was available in six lesions (four resections, two biopsies). The following distribution of enhancement patterns was observed: 10/26 homogeneously hyperintense, 4/26 inhomogeneously hyperintense, 5/26 iso-intense, 6/26 hypointense-with-ring, and 1/26 hypointense, but without enhancing ring. The following histological features associated with gadoxetic-acid uptake were identified: number and type of bile-ducts (pre-existent bile-ducts, proliferation, and metaplasia), extent of fibrosis, the presence of inflammation and extent of vascular proliferation.Conclusion
FNH lesions can be categorized into different hepatobiliary enhancement patterns on Gadoxetic-acid-enhanced MRI, which appear to be associated with histological differences in number and type of bile-ducts, and varying the presence of fibrous tissue, inflammation, and vascularization. 相似文献99.
Facilitation of avoidance behavior by vasopressin fragments microinjected into limbic-midbrain structures 总被引:1,自引:0,他引:1
Effects of arginine vasopressin (AVP1-9) and its behaviorally active fragments [Cyt6]AVP5-9 and [Cyt6]AVP5-8 were studied on the retention of one-trial learning passive avoidance behavior in rats. Peptides were microinjected into various limbic and midbrain structures (ventral or dorsal hippocampus or the dorsal raphe nucleus) and were administered either immediately after the learning trial (post-learning treatment) or shortly before the 24 h retention session (pre-retention treatment). Doses for intracerebral microinjections were selected after preliminary experiments with subcutaneous and intracerebroventricular peptide administration. AVP1-9 facilitated passive avoidance behavior when the peptide was microinjected into either brain structure, however, the ventral hippocampus appeared to be the most sensitive. In this limbic region, AVP1-9 facilitated passive avoidance behavior in an amount of 8 pg (bilaterally), both when given as post-learning or pre-retention treatment. [Cyt6]AVP5-9 and [Cyt6]AVP5-8 were more effective than the parent nonapeptide in terms that a lower amount of these peptide fragments facilitated passive avoidance behavior in all brain regions investigated. The ventral hippocampus appeared to be the most sensitive brain site for the behaviorally active vasopressin fragments as well. Following microinjections into the ventral hippocampus, [Cyt6]AVP5-8 was more effective in a post-learning than in a pre-retention treatment schedule. [Cyt6]AVP5-9 on the other hand was more effective when injected shortly before the retention trial. The data indicate that limbic-midbrain structures are sensitive to AVP1-9 and behaviorally active putative metabolites of this neuropeptide. The active fragments selectively influence different phases of information processing upon limbic microinjections. 相似文献
100.