共查询到10条相似文献,搜索用时 180 毫秒
1.
Sheila Wang Stephen G. Matthews Treena M. Jeffray M. Yvette Stevens Kaiping Yang Geoffrey L. Hammond John R. G. Challis 《Endocrine》1997,6(3):271-278
Activation of the hypothalamic-pituitary-adrenal (HPA) axis of fetal sheep during late gestation is associated with increases
in plasma concentrations of adrenocorticotropic hormone (ACTH) and cortisol, and ultimately results in parturition. However,
the mechanisms contributing to the concurrent increases in ACTH and cortisol are unclear. Plasma estradiol-17β (E2) concentrations increase progressively in the prepartum ovine fetus, and we hypothesized that E2 may influence HPA activity by affecting either basal and/or hypoxemia-stimulated ACTH release. We examined potential mechanisms,
including altered expression of pro-opiomelanocortin (POMC) in fetal pituitary corticotrophs, and changes in corticosteroid
binding globulin (CBG) and/or the enzymes 11β hydroxy steroid dehydrogenase (11β HSD)-1 or 11β HSD-2 in liver and placenta,
that could alter negative feedback control. We infused fetal sheep at 127 d of gestation with either E2 (100 μg/24 h) or saline for 100 h. Fetal arterial blood samples were collected at 8 h intervals during the infusion of E2 or saline (n=4), for measurement of basal plasma ACTH and cortisol concentrations, as well as plasma corticosteroid binding capacity (CBC).
Placenta and fetal liver samples were collected at 100 h for measurement of placental 11 β HSD-1 and 11β HSD-2 mRNA and hepatic
CBG and 11β HSD-1 mRNA, by Northern blotting. Fetal pituitary samples were collected for measurement of POMC mRNA byin situ hybridization. In a separate experiment, fetuses were exposed to 2 h of hypoxemia at 75 h of E2 or saline infusion (n=4), and fetal arterial blood samples were collected during the period of hypoxemia for measurement of plasma ACTH and cortisol
concentrations. E2 infusion had no effect on basal plasma concentrations of ACTH or total cortisol, or on the stimulated levels of ACTH or total
cortisol achieved in response to hypoxemia. Basal fetal pituitary POMC mRNA also did not change significantly with E2 infusion. No significant increases were observed in plasma CBC during E2 administration. However, hepatic CBG and 11β HSD-1 mRNA were significantly elevated in the livers of E2-treated fetuses. Placental 11β HSD-1 mRNA; but not 11β HSD-2 mRNA was increased by E2 treatment. These data do not support a direct effect of exogenous E2 at the level of basal or hypoxemia-stimulated ACTH output, but suggest that elevated E2 concentrations may alter the expression of genes encoding proteins implicated in tonic regulation of fetal HPA function. 相似文献
2.
Barney M Call GB McIlmoil CJ Husein OF Adams A Balls AG Oliveira GK Miner EC Richards TA Crawford BK Heckmann RA Bell JD Judd AM 《Endocrine》2000,13(3):369-377
Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) are synthesized and released from adrenal cells. Therefore, the effects
of TNF-α and IL-6 on cortisol release from bovine zona fasciculata (ZF) cells were investigated. IL-6 (10–1000 pg/mL) significantly
increased basal and adrenocorticotropic hormone (ACTH)-stimulated cortisol release in a concentration-dependent manner. This
stimulatory effect of IL-6 became apparent at intervals as short as 4 h and continued through 24 h. IL-6 also potentiated
the cortisol release stimulated by the adenylyl cyclase activator forskolin. By contrast, TNF-α (0.1–10 ng) inhibited basal
and ACTH-stimulated cortisol release in a concentration-dependent manner. The inhibitory effects of TNF-α on cortisol release
were significant at time intervals as short as 4 h and continued through 24 h. TNF-α inhibited forskolin-stimulated cortisol
release. Binding studies demonstrated that ZF cells have IL-6 receptors (100 receptors/cell, K
d of 7.5×10−11) and TNF receptors (200 receptors/cell, K
d of 2.4×10−9
M). Immunohistochemical analysis provided evidence that the majority of ZF cells have IL-6 receptors, TNF type 1 receptors,
and TNF type 2 receptors. Because IL-6 and TNF-α are released from the adrenal cortex and these cytokines modify the release
of cortisol from the ZF, IL-6 and TNF-α may play a paracrine or autocrine role in the regulation of adrenal function. 相似文献
3.
Variations in peripheral plasma corticosterone levels in male iguanid lizards, Sceloporus cyanogenys, were investigated under varying physiological conditions. Control baseline levels of the steroid in plasma were significantly decreased by hypophysectomy, adrenalectomy, hypothalamic lesions, and cyanoketone, an inhibitor of Δ5-3β hydroxysteroid dehydrogenase. Levels were increased following treatment with mammalian ACTH in both intact and hypophysectomized lizards. In the intact animal, ACTH produced a more rapid, more prolonged, and quantitatively greater response of the adrenal gland than the same hormone when administered to the hypophysectomized animal. An apparent increase in corticosterone levels was observed following metyrapone (an 11β-hydroxylase inhibitor) treatment, and aminoglutethimide, an inhibitor of the formation of pregnenolone from cholesterol, had no effect. 相似文献
4.
Givalois L Gaillet S Mekaouche M Ixart C Bristow AF Siaud P Szafarczyk A Malaval F Assenmacher I Barbanel G 《Endocrine》1995,3(7):481-485
We have recently shown that total lesion of the ventral noradrenergic bundle (VNAB-X), enhanced the short-lived (<120 min)
triggering effect of intra-arterially (i.a.) given IL-1β on plasma ACTH levels. In the present study we used the same VNAB-X
paradigm to explore the mechanisms of the long-lived (480 min) LPS stimulatory effect on plasma ACTH, corticosterone (CORT)
and IL-1β levels. In control rats, 25 μg kg−1 LPS induced a 20-fold increase in ACTH and a 7-fold increase in CORT concentrations at 30 min, which continued to rise until
60 min, before receding to baseline at 480 min. In contrast, the plasma IL-1β concentration started to increase above undetectable
levels only at 120 min. In VNAB-X animals, the early (30 min) ACTH/CORT response to LPS was completely blunted, and the ACTH
surge was reduced by 75% at 60 min. However, the sustained hormonal response (120 to 480 min) was unaltered. Both the temporal
pattern and the amplitude of the plasma IL-1β response were normal. We conclude that (1) the VNAB is involved in the early
(first 60 min) ACTH/CORT response to systemic LPS, (2) plasma IL-1β does not appear to be associated with this early corticotropic
activation and (3) the later stages of the ACTH/CORT response to LPS (60 to 480 min) appear to be independent of the VNAB
control and may therefore involve different control mechanisms, in which the IL-1β, by this stage massively released in the
blood, may play a major role. 相似文献
5.
Interleukin-6 (IL-6) and tumor necrosis factor (TNF) are secreted by rat adrenal zona glomerulosa cells. Serotonin increases
the release of aldosterone, corti-costerone, and cortisol from the adrenal cortex. Therefore, the effects of serotonin on
IL-6 and TNF release from rat adrenal zona glomerulosa cells were investigated. Cultures of rat adrenal zona glomerulosa cells
were enzymatically prepared and cultured for 4–6 d. The cells were then exposed to serum-free RPMl-1640 medium containing
vehicle (RPMl medium alone), serotonin, and/or endotoxin, interleukin-1β, or adrenocorticotrophic hormone (ACTH). Following
a 5-h incubation, medium was removed from the cells, and IL-6 and TNF content of this medium determined with bioassays. Serotonin
(1–1000 nM) increased basal IL-6 release from zona glomerulosa cells, but inhibited basal TNF release from these cells. Endotoxin and
interleukin-1β (IL-1β) increased IL-6 and TNF release from zona glomerulosa cells. Serotonin potentiated IL-6 release stimulated
by endotoxin and IL-1β, but inhibited TNF release stimulated by these agents. Serotonin potentiated ACTH-stimulated IL-6 release.
Serotonin had no effect on IL-6 release from rat anterior pituitary cells. Because IL-6, TNF, and serotonin modify the release
of aldosterone and glucocorticoids from adrenal cells, the stimulatory effects of serotonin on aldosterone and glucocorticoid
release may be mediated in part by the effects of serotonin on IL-6 and TNF release from adrenal cells. 相似文献
6.
Dennis Schulster Malcolm C. Richardson John W. Palfreyman 《Molecular and cellular endocrinology》1974,2(1):17-29
The kinetics of the corticosteroidogenic response to adrenocorticotrophin (ACTH) have been investigated using collagenase dispersed adrenocortical cells. Following the addition of ACTH at a concentration that was maximal for steroidogenesis, there was a time-lag of about 3 min before increased steroidogenesis became apparent. This lag was extended (about two-fold) in the presence of a half-maximal concentration of ACTH. Preincubation of cells with submaximal concentrations of both cycloheximide and puromycin extended the time-lag observed following ACTH addition. Increasing doses of cycloheximide or puromycin concomitantly inhibited protein synthesis and steroidogenesis. Moreover cycloheximide, at a dose that halved protein synthesis, also inhibited steroidogenesis by 54–61% for a range of ACTH concentrations (1 × 10−4 to 1 × 10−2 I.U./ml).It is concluded that the delay before ACTH-stimulated steroidogenesis is not attributable solely to the time taken for ribosomes to read of from the mRNA strand, the code for protein regulator(s). The results are discussed in terms of steroidogenic mechanisms whereby ACTH either induces de novo protein synthesis or activates a pre-existing, but labile, protein. In this latter scheme the steroidogenic rate observed under various conditions would be directly dependent upon the intracellular level of such an activated protein regulator. The half-life of labile protein, implicated as regulating steroidogenesis, was estimated at 2–4 min in this adrenal cell suspension system. 相似文献
7.
S. Miyazaki T. Yoshikawa A. Hashiramoto R. Yamada Y. Tsubouchi M. Kohno Y. Kawahito M. Kondo H. Sano 《Modern rheumatology / the Japan Rheumatism Association》2002,12(3):0206-0212
Adrenocorticotropic hormone (ACTH) and another pro-opiomelanocortin-derived neuropeptide, β-endorphin (β-End), are stimulated
by corticotropin-releasing hormone (CRH) at the anterior pituitary. CRH and β-End have predominantly proinflammatory effects
in peripheral inflammatory sites. We have supposed that inflammatory stimuli develop ACTH as well as β-End. In this study,
we investigated the expression of ACTH in inflamed synovial tissue from patients with rheumatoid arthritis (RA) and osteoarthritis
(OA), and at inflammatory joints with adjuvant-induced arthritis (AA) in female Lewis (LEW/N) rats. The expression of ACTH
immunostaining was significantly greater in synovium of RA patients than in that of OA patients (P < 0.0001), and correlated with the extent of inflammatory mononuclear cell infiltration. Extensive and intense intracellular
ACTH immunostaining, which correlated with the advance in arthritis score, was observed in the synovial lining layer, inflammatory
mononuclear cells, and fibroblast-like cells of synovium and chondrocytes in LEW/N rats with AA. In addition, we performed
double immunostaining of the same sections from arthritic joints in rats with anti-ACTH and anti-CRH antibodies. ACTH and
CRH colocalized in inflammatory mononuclear cells and fibroblast-like cells. ACTH may play a role in the pathogenesis of RA
as well as CRH.
Received: July 4, 2001 / Accepted: January 23, 2002
Correspondence to: H. Sano 相似文献
8.
Objective To estimate the dose dependence of endogenous ACTH stimulation of adrenal cortisol secretion overnight. Design Ten‐minute sampling for ACTH and cortisol over 8 and 24 h (n = 17), after metyrapone administration (n = 6), during an insulin‐tolerance test (n = 7). Subjects Healthy adults. Measurements ACTH dose‐responsive estimates. Results Twenty‐four hour ACTH–cortisol concentration pairs yielded an estimated EC50 (one‐half maximally stimulatory ACTH concentration) of 5·1 (2·2–9·5) pmol/l [median (range)]. This did not differ from EC50s based on 8‐ or 6‐h data [5·9 (3·5–11) and 7·5 (3·7–41) pmol/l] in the same individuals. ACTH efficacy (maximally stimulatable cortisol secretion rate) was 8·4 (3·1–20), 11 (5·9–24) and 15 (5·9–22) nmol/l/min, when calculated over 24, 8 and 6 h, respectively (P = NS). Adrenal sensitivity (slope term) was also consistent across sampling durations, viz. 14 (1·3–95), 18 (1·3–64) and 20 (1·3–64) slope units. Compared with placebo, metyrapone reduced ACTH efficacy from 11 (6·2–62) to 2·8 (1·5–4·5) nmol/l/min for cortisol (n = 9, P < 0·001), while increasing ACTH efficacy for 11‐desoxycortisol from 2·3 (0·9–2·9) to 99 (70–218) nmol/l/min (n = 6, P < 0·01), thus affirming face validity. Combined ACTH and cortisol responses to hypoglycaemia allowed an estimate of ACTH efficacy of 28 (22–81) nmol/l/min, compared with the control value of 8·7 (5·6–26), suggesting enhanced adrenal responsiveness. Conclusions The results suggest that endogenous ACTH–adrenal drive can be approximated from overnight 8‐h sampling of paired ACTH and cortisol concentrations. This strategy may have merit in clinical research in childhood, pregnancy, anxiety states and frail elderly individuals, when ACTH injections are not desired. 相似文献
9.
Yukioka M Komatsubara Y Yukioka K Toyosaki-Maeda T Yonenobu K Ochi T 《Modern rheumatology / the Japan Rheumatism Association》2006,16(1):30-35
To assess adrenal function with respect to the presence or absence of steroid therapy, we investigated differences in the
blood levels of adrenocorticotropic hormone (ACTH) and dehydroepiandrosterone sulfate (DHEAS) in relation to steroid (prednisolone)
administration in 123 patients with rheumatoid arthritis (RA). Levels of ACTH and DHEAS were significantly lower in the steroid-treated
group than in the non-treated group (ACTH: 11.79 pg/ml vs 27.92 pg/ml) (DHEAS: 418.12 ng/ml vs 883.91 ng/ml) (P < 0.0001). We observed no steroid dose-related differences in ACTH levels. However, DHEAS levels showed a slight decrease
at a prednisolone dose of 2.5 mg/day, with a significant decrease being observed at a dose of 5 mg/day when statistical adjustments
were made for age and sex (P < 0.0001). At doses of 7.5 mg/day or greater, DHEAS levels were significantly lower than those for 5 mg/day (P < 0.0006). These results suggest that low-dose prednisolone reduces adrenal function in patients with RA. We recommend that
doses of prednisolone should be limited to 5 mg/day or less in consideration of adrenal function when treating RA patients.
The measurement of ACTH and DHEAS may be useful for evaluating adrenal function in patients with RA. 相似文献
10.
Relationships among adrenal weight, corticosterone, and stimulated adrenocorticotropin levels in rats 总被引:1,自引:0,他引:1
Based on results of previous studies, we tested the hypothesis that increased adrenal weight in the absence of increased corticosterone secretion would inhibit the magnitude of the ACTH response to ether vapor. Adrenal hypertrophy was induced by treatment of rats for 3 days with aminoglutethimide, cyanoketone, or metyrapone, three agents that act to inhibit enzymes required for corticosterone synthesis. On the fourth day, resting plasma ACTH and corticosterone levels were normal; however, the logarithm of the ACTH response to ether was directly related to total adrenal weight. This result did not support the hypothesis. Unilateral adrenalectomy and treatment with cyanoketone resulted in total adrenal weight equivalent to that of control rats bearing two adrenals. Resting ACTH levels were normal, but stimulated ACTH was significantly greater in these rats than in controls or in rats with two adrenals, suggesting that there is an interaction between the effects of unilateral adrenalectomy and adrenal enzyme inhibition. As anticipated, adrenal hypertrophy with increased corticosterone production caused by ACTH infusion resulted in a significant negative relationship between resting and stimulated ACTH levels and adrenal weight. We conclude that when adrenals are enlarged by means that prevent excessive corticosterone secretion, there is a mechanism associated with the increase in adrenal weight that correlates directly with the magnitude of stimulated ACTH secretion. We have reexamined the results of our previous results in the light of these experiments. 相似文献