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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To assess the interaction among androgens, placenta, and the hypothalamo-pituitary-adrenal axis we studied effects of androstenedione administered intravascularly to the pregnant monkey on maternal plasma CRH, ACTH, dehydroepiandrosterone sulfate (DHEAS), cortisol, and estradiol concentrations. Ten monkeys (128 +/- 3 days gestation; mean +/- SEM) were instrumented under general halothane anesthesia with maternal femoral artery and venous catheters and uterine electromyogram electrodes. At 137-144 days gestation, baseline maternal femoral artery samples for CRH, ACTH, DHEAS, cortisol, and estradiol measurements were taken at 1.5-h intervals for 7 h starting 2 h before darkness. On the following day, a continuous iv androstenedione infusion (0.3 mg/kg.min at 0.25 ml/h) in 10% intralipid was started at 0930 h in four monkeys; the other six animals received vehicle alone at the same rate starting at the same time. Maternal blood sampling was repeated 1 and 3 days after androstenedione or vehicle administration. Maternal plasma CRH, ACTH, DHEAS, cortisol, and estradiol levels were unaffected by intralipid. In contrast, androstenedione infusion produced a sustained increase in maternal plasma estradiol and a sustained fall in maternal plasma ACTH, but did not affect maternal plasma CRH, DHEAS, or cortisol concentrations. These results provide evidence for negative feedback regulation by androgens at the hypothalamo-pituitary-adrenal axis in the pregnant monkey. Lack of inhibition of maternal plasma CRH after androstenedione administration supports differential regulation of hypothalamic and placental CRH by androgens.
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PMID:Effect of androstenedione administration on the maternal hypothalamo-pituitary-adreno-placental axis in the pregnant rhesus monkey. 859 9

The purpose of this study was to determine whether a short period (5 days) of night-shift work affected the pituitary-adrenal responses to CRH. Ten nurses (8 female and 2 male; age 28.1 +/- 1.7 yr: mean +/- SEM) working at the Royal Liverpool University Hospital, and who regularly undertook periods of night and day shift work were enrolled. Measurements were made of basal ACTH and cortisol concentrations, and their responses to iv ovine CRH (1 microgram.kg-1). Basal ACTH concentrations were higher during the night shift than during the day shift (12.9 +/- 5.1 pmol.L-1 vs. 4.7 +/- 1.2 pmol.L-1, P < 0.01) whereas cortisol concentrations were lower (551 +/- 48 nmol.L - 1 vs. 871 +/- 132 nmol.L - 1, P < 0.01). After CRH injection, ACTH concentrations remained consistently higher during the night shift, but the integrated increase in ACTH concentration was lower (P < 0.05) than during the day shift. Conversely, the increase in cortisol concentration was greater during the night shift than the day shift (283 +/- 53 nmol.L-1 vs. 134 +/- 41 nmol.L-1, P < 0.05). We conclude that the pituitary-adrenal responses to CRH are markedly disrupted after only 5 days of nighttime work. These abnormalities mimic those previously observed in patients with chronic fatigue syndrome. Neuroendocrine abnormalities reported to be characteristic of chronic fatigue syndrome may be merely the consequence of disrupted sleep and social routine.
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PMID:Short-term night-shift working mimics the pituitary-adrenocortical dysfunction in chronic fatigue syndrome. 862 49

To evaluate the pituitary-adrenal reserve and to standardize the methodology of performing the human CRH (hCRH) stimulation test, we performed the hCRH test on 14 preterm (< 32 gestational weeks), very low birth weight infants, who did not receive antenatal or postnatal corticosteroid treatment, on days 7 and 14 of life. Blood samples were obtained 0 (baseline), 15, 30, and 60 min after an iv dose of hCRH (1 microgram/kg). The plasma ACTH concentration rose from a basal value of 5.7 +/- 0.6 pmol/L (mean +/- SEM) to 11.9 +/- 2.1 pmol/L (P < 0.005), 9.2 +/- 1.2 pmol/L (P < 0.005), and 7.7 +/- 0.8 pmol/L (P < 0.005) at 15, 30, and 60 min, respectively. The corresponding rises in serum cortisol from a basal concentration of 396 +/- 67 nmol/L were 509 +/- 71 nmol/L (P < 0.0001), 647 +/- 62 nmol/L (P < 0.0001), and 578 +/- 60 nmol/L (P < 0.0001). The plasma ACTH concentration consistently peaked early at 15 min, whereas the maximum cortisol response occurred 30 min post-hCRH stimulation. No significant differences were detected between the hCRH tests performed on days 7 and 14 (P > 0.15). Mechanical ventilation, infant gender, and mode of delivery did not significantly influence the hormonal responses (P > 0.25). We have defined in this study the pattern, the magnitude of the pituitary-adrenal response, and the timing of the peak concentrations of plasma ACTH and serum cortisol in relation to a standard iv dose of hCRH. The hCRH test in very low birth weight infants appears to be safe and reproducible, and produces a pituitary-adrenal response comparable to that seen in older children and adults, indicating that pituitary-adrenal function is mature at these early stages of gestation.
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PMID:The pituitary-adrenal responses to exogenous human corticotropin-releasing hormone in preterm, very low birth weight infants. 906 85

Within the central nervous system, glucagon-like peptide-1-(7-36) amide (GLP-1) acts as a transmitter, inhibiting feeding and drinking behavior. Hypothalamic neuroendocrine neurons are centrally involved in the regulatory mechanisms controlling these behaviors, and high densities of GLP-1 binding sites are present in the rat hypothalamus. In the present study we have, over a period of 4 h, followed the effect of centrally injected GLP-1 on plasma levels of the neurohypophysial hormones vasopressin and oxytocin. Plasma levels of corticosterone and glucose were also followed across time after central administration of GLP-1. In conscious, freely moving, and unstressed rats, central injection of GLP-1 significantly elevated plasma levels of vasopressin 15 and 30 min after administration (basal, 0.8 +/- 0.2 pg/ml; 15 min, 7.5 +/- 2.0 pg/ml; 30 min, 5.6 +/- 1.1 pg/ml; mean +/- SEM) and elevated corticosterone 15 min after administration (52 +/- 13 vs. 447 +/- 108 ng/ml, basal vs. 15 min; mean +/- SEM). In contrast, plasma oxytocin levels were unaffected by intracerebroventricular (icv) injections of GLP-1 over a period of 4 h after the injection. The animals given a central injection of GLP-1 developed transient hypoglycemia 20 min after the injection, which was fully restored to normal levels at 30 min. Furthermore, we used c-fos immunocytochemistry as an index of stimulated neuronal activity. The distribution and quantity of GLP-1-induced c-fos immunoreactivity were evaluated in a number of hypothalamic neuroendocrine areas, including the magnocellular neurons of the paraventricular (PVN) and supraoptic (SON) nuclei and the parvicellular neurons of the medial parvicellular subregion of the PVN. The number of c-fos-expressing nuclei in those areas was assessed 30, 60, and 90 min after icv administration of GLP-1. Intracerebroventricular injection of GLP-1 induced c-fos expression in the medial parvicellular subregion of the PVN as well as in magnocellular neurons of the PVN and SON. A slight induction of c-fos expression was seen in the arcuate nucleus and the nucleus of the solitary tract, including the area postrema. In contrast, the subfornical organ, which is a rostrally situated circumventricular organ, was free of c-fos-positive cells after central administration of GLP-1. When the GLP-1 antagonist exendin-(9-39) was given before the GLP-1, c-fos expression in these neuroendocrine areas was almost completely abolished, suggesting that the effect of GLP-1 on c-fos expression is mediated via specific receptors. A dual labeling immunocytochemical technique was used to identify the phenotypes of some of the neurons containing c-fos-immunoreactive nuclei. Approximately 80% of the CRH-positive neurons in the hypophysiotropic medial parvicellular part of the PVN coexpressed c-fos 90 min after icv GLP-1 administration. In contrast, very few (approximately 10%) of the vasopressinergic magnocellular neurons of the PVN/SON contained c-fos-positive nuclei, whereas approximately 38% of the magnocellular oxytocinergic neurons expressed c-fos-positive nuclei in response to GLP-1 administration. This study demonstrates that central administration of the anorectic neuropeptide GLP-1 activates the central CRH-containing neurons of the hypothalamo-pituitary-adrenocortical axis as well as oxytocinergic neurons of the hypothalamo-neurohypophysial tract. Therefore, we conclude that GLP-1 activates the hypothalamo-pituitary-adrenocortical axis primarily through stimulation of CRH neurons, and this activation may also be responsible for the inhibition of feeding behavior.
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PMID:Central administration of glucagon-like peptide-1 activates hypothalamic neuroendocrine neurons in the rat. 932 62

The cytokine interleukin-1 (IL-1) can act within the brain to induce peripheral endocrine and immune effects. In the rodent intracerebroventricular (i.c.v.) injection of IL-1 activates the hypothalamic-pituitary-adrenal axis and suppresses peripheral immune function by a CRH-dependent mechanism. It is unknown if IL-1 can similarly act within the brain to cause peripheral immunosuppression in the primate and to what extent this could be attributed to the IL-1-induced increase in ACTH and cortisol levels. In this study we have characterized the pituitary-adrenal and peripheral lymphocyte responses to IL-1 alpha (4.2 micrograms) infused over 30 min into the lateral ventricle of ovariectomized monkeys (n = 5) as compared with responses to an intravenous (i.v.) ACTH infusion (1 microgram/h for 7 h; n = 4). Four serial blood samples were obtained for ACTH and cortisol determination and for lymphocyte isolation during a 1-hour baseline and for 7 h after IL-1 or ACTH. Lymphocyte proliferation was measured by 3H-thymidine uptake in response to stimulation with phytohemagglutinin. In all 5 animals, IL-1 alpha caused rapid and profound suppression of lymphocyte mitogen responsiveness for 7 h. Baseline lymphocyte proliferation was 51,800 +/- 9,780 cpm and suppressed to a nadir of 4.5% with a mean of 23% baseline over 7 h (p < 0.001). Mean ACTH and cortisol levels increased from 33 +/- (SEM) 4.6 pg/ml and 43 +/- 4.0 micrograms/dl, respectively, during the control period to 90 +/- 14 pg/ml and 56 +/- 2.6 micrograms/dl, respectively, after IL-1 (p < 0.01). Before i.v. ACTH, baseline lymphocyte proliferation was 49,400 +/- 2,820 cpm, and suppressed to a mean of 64% of baseline during ACTH infusion (p < 0.05). Mean ACTH and cortisol levels increased from 48 +/- 5.0 pg/ml and 43 +/- 2.0 micrograms/dl, respectively, to 170 +/- 34 pg/ml and 66 +/- 2.3 micrograms/dl, respectively, during the ACTH infusion (p < 0.01). Lymphocyte suppression after i.c.v. IL-1 was much more profound than after i.v. ACTH (p < 0.01); the area under the IL-1 response curve was 37% of the area under the ACTH response curve. These studies demonstrate for the first time in the primate that centrally injected IL-1 has a profound suppressive effect on lymphocyte function. They also show for the first time in any species that there appears to be a significant immunosuppressive message produced by i.c.v. IL-1 that is not accounted for by the associated increases in ACTH and cortisol.
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PMID:Intracerebroventricular injection of interleukin-1 suppresses peripheral lymphocyte function in the primate. 932 40

Hexarelin (HEX) is a synthetic growth-hormone-releasing peptide (GHRP) which acts via specific receptors at both the pituitary and the hypothalamic level to stimulate GH release both in animals and in man. Like other GHRPs, HEX possesses also significant prolactin- and adrenocorticotropin (ACTH) cortisol-releasing activity, but the mechanisms underlying these effects are even less clear. To clarify the mechanisms by which HEX stimulates the pituitary-adrenal axis in man, in 7 healthy young volunteers we studied the effects of HEX (2.0 microg/kg i.v.) and/or human corticotropin-releasing hormone (hCRH; 2.0 microg/kg i.v.) and/or arginine vasopressin (AVP; 0.17 U/kg i.m.) on ACTH and cortisol secretion. The GH responses to HEX alone and combined with hCRH and/or AVP were also studied. HEX increased ACTH and cortisol secretion (peak, mean +/- SEM: 26.3 +/- 5.1 vs. 15.8 +/- 3.1 pg/ml and 145.0 +/- 11.4 vs. 131.7 +/- 11.7 microg/l, p < 0.01, respectively) to levels overlapping with those induced by AVP (27.9 +/- 6.1 vs. 13.1 +/- 3.5 pg/ml and 167.6 +/- 16.2 vs. 113.3 +/- 9.4 microg/l, p < 0.01, respectively) and similar to those elicited by hCRH (28.1 +/- 4.6 vs. 17.4 +/- 3.1 pg/ml and 182.7 +/- 22.8 vs. 114.8 +/- 12.3 microg/l, p < 0.02, respectively). The ACTH but not the cortisol response to hCRH was higher (p < 0.02) than those to HEX when evaluated as area under the curve. The co-administration of HEX and AVP had no significant interaction on ACTH and cortisol peak levels (40.7 micro 5.3 pg/ml and 168.8 +/- 13.5 microg/l, respectively). On the other hand, the co-administration of HEX and hCRH had a less than additive effect on ACTH and cortisol secretion (53.3 +/- 11.2 pg/ml and 204.0 +/- 13.7 microg/l, respectively). CRH and AVP had a true synergistic effect on ACTH (104.9 +/- 14.2 pg/ml, p < 0.01) and an additive effect on cortisol secretion (281.3 +/- 10.8 microg/l, p < 0.02). HEX did not modify the effect of CRH + AVP on both ACTH (135.5 +/- 22.0 pg/ml) and cortisol secretion (261.1 +/- 13.2 microg/l). The GH response to HEX (55.7 +/- 19.8 vs. 2.7 +/- 1.9 microg/l, p < 0.005) was unaffected by the administration of CRH alone (53.5 +/- 21.0 microg/l) and/or AVP co-administration (60.2 +/- 21.2 and 45.9 +/- 10.6 microg/l, respectively). In conclusion, the results of this study demonstrate that GHRPs, beside their well-known GH-releasing activity, possess a remarkable ACTH-releasing activity, overlapping with that of AVP and similar to that of hCRH, two neurohormones which are known to play the major role in the control of the pituitary-adrenal axis. It is noteworthy that HEX shows no synergistic effect with either AVP or hCRH which, on the other hand, truly synergize. This evidence suggests the hypothesis that the ACTH-releasing activity of GHRPs could be, at least partially, independent of both CRH- and AVP-mediated actions in humans.
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PMID:Hexarelin, a synthetic growth-hormone releasing peptide, shows no interaction with corticotropin-releasing hormone and vasopressin on adrenocorticotropin and cortisol secretion in humans. 943 Apr 49

To establish the factors that modulate circulating CRH-binding protein (CRH-BP) levels, we measured plasma CRH-BP in patients with a variety of endocrine and systemic disorders. CRH-BP was measured by RIA. Young women have higher plasma levels of CRH-BP than young men [females (n = 18), mean +/- SEM, 145 +/- 7; males (n = 20), 99 +/- 6 ng/mL; P < 0.0001], but levels do not fall with the menopause or vary during the menstrual cycle and are unaffected by estrogen replacement therapy. Levels were lower in patients with liver disease than in healthy men (26 +/- 3 vs. 99 +/- 6; P < 0.0001) and were elevated in chronic renal failure compared to those in healthy women (211 +/- 11.2 vs. 145 +/- 7; P < 0.01). Levels were unaffected by fasting in men or women (male fasted, 97 +/- 11; male fed, 97 +/- 8; female fasted, 136 +/- 9; female fed, 152 +/- 10). Dexamethasone treatment lowered CRH-BP in all subjects (129 +/- 8 vs. 111 +/- 9; P < 0.003). Similarly, CRH-BP levels were lower in patients with Cushing's syndrome (all female) than in healthy female controls (median, 82; range, 53-106; vs. median, 142; range, 101-190; P < 0.0001). In Cushing's patients, an i.v. bolus of 100 micrograms human CRH further lowered plasma CRH-BP at 15 min (81 +/- 5 vs. 50 +/- 4; P < 0.0003). Plasma levels of CRH-BP are higher in women than men, but this is unrelated to circulating estrogen levels. The low levels in liver disease and the high levels in renal failure support its hepatic origin and the kidneys as the route of clearance from plasma. The ability of glucocorticoids and exogenous CRH to lower plasma CRH-BP levels and of CRH-BP to modulate the bioactivity of circulating CRH suggest that the protein may be an important regulator of circulating CRH or related ligands.
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PMID:The pathophysiology of circulating corticotropin-releasing hormone-binding protein levels in the human. 958 64

Hexarelin (HEX) is a synthetic GHRP which acts on specific receptors at both the pituitary and the hypothalamic level to stimulate GH release both in animals and in humans. Like other GHRPs, HEX possesses also acute ACTH and cortisol-releasing activity similar to that of hCRH. The mechanisms underlying the stimulatory effect of GHRPs on hypothalamo-pituitary-adrenal (HPA) axis are still unclear, although a CNS-mediated action has been demonstrated. In 6 normal healthy young women (26-34 years) we studied the effects on ACTH and cortisol secretion of HEX (2.0 microg/kg i.v. at 0 min) alone and preceded by dexamethasone (DEXA, 1 mg p.o. at 23.00 h on the previous night) or alprazolam (ALP, 0.02 mg/kg p.o. at -90 min), a benzodiazepine which binds to GABA receptors and possesses CRH-mediated inhibitory activity on HPA axis. ACTH and cortisol secretion after saline administration as well as the GH response to HEX alone and preceded by DEXA or ALP were also studied. HEX administration elicited an increase in ACTH (peak vs. baseline, mean +/- SEM: 28.0 +/- 6.7 vs. 11.7 +/- 2.2 pg/ml, p < 0.05) and cortisol secretion (162.6 +/- 15.0 vs. 137.7 +/- 12.6 microg/l, p < 0.05). DEXA pretreatment strongly inhibited basal ACTH (3.2 +/- 0.7 pg/ml, p < 0.01) and cortisol levels (11.3 +/- 2.5 microg/l, p < 0.001) and abolished the ACTH and cortisol responses to HEX (3.6 +/- 0.9 pg/ml, p < 0.01 and 10.7 +/- 2.0 microg/l, p < 0.001), respectively. On the other hand, ALP pretreatment did not significantly modify basal ACTH (7.9 +/- 2.0 pg/ml) and cortisol levels (127.6 +/- 14.5 microg/l) but abolished the HEX-induced ACTH and cortisol secretions (8.6 +/- 2.4 pg/ml, p < 0.05 and 111.0 +/- 6.0 microg/l, p < 0.05), respectively. ACTH and cortisol levels after HEX when preceded by ALP overlapped with those recorded during saline. HEX induced a clear GH response (peak at 15 min vs. baseline: 65.5 +/- 20.5 vs. 2.2 +/- 0.7 microg/l, p < 0.03) which was blunted by ALP (peak at 15 min: 21.5 +/- 5.5 microg/l, p < 0.05) while it was not modified by DEXA pretreatment (78.7 +/- 7.6 microg/l). In conclusion, our present data demonstrate that the ACTH- and cortisol-releasing effect of HEX is abolished by either dexamethasone or alprazolam, a benzodiazepine, which is even able to blunt the GH-releasing activity of the hexapeptide. These findings suggest that, in physiological conditions, the stimulatory effect of GHRPs on HPA axis is sensitive to the negative glucocorticoid feedback and could be mediated by GABAergic mechanisms; the latter seem also involved in the GH-releasing activity of GHRPs.
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PMID:Effects of dexamethasone and alprazolam, a benzodiazepine, on the stimulatory effect of hexarelin, a synthetic GHRP, on ACTH, cortisol and GH secretion in humans. 964 12

We previously reported that in Cushing's disease (CD) the ACTH- and cortisol (F)-releasing activity of Hexarelin (HEX), a GH secretagogue, is exaggerated with respect to that in normal subjects and is higher than that of human CRH (hCRH), but it is absent in Cushing's syndrome. Our aim was to extend the study about the effects of HEX (2.0 microg/kg, iv) on ACTH and F secretion in 21 patients with CD (3 men and 18 women, 16-68 yr old). Based on magnetic resonance imaging, 15 CD patients had pituitary microadenoma, and 6 had macroadenoma. The results in CD patients were compared with those in 27 normal age-matched controls (NS; 10 men and 17 women, 24-69 yr old). Basal ACTH and F levels in CD were similar in patients with microadenom (mean+/-SEM, 78.3+/-7.2 pg/mL and 237.1+/-23.6 microg/L, respectively) and macroadenoma (57.4+/-9.0 pg/mL and 196.9+/-20.1 microg/L, respectively) and were higher (P < 0.001) than those in NS (17.7+/-2.0 pg/mL and 115.3+/-6.7 microg/L, respectively). In microadenoma CD patients, HEX induced marked ACTH and F increases (delta peak, mean+/-SEM: 261.2+/-77.6 pg/mL and 226.1+/-87.2 microg/L, respectively), which were higher (P < 0.04) than those induced by hCRH (45.6+/-16.9 pg/mL and 84.6+/-25.7 microg/L, respectively). Moreover, in microadenoma CD patients, the ACTH and F responses to HEX were higher (P < 0.001) than those in NS (18.5+/-4.0 pg/mL and 36.1+/-6.8 microg/L, respectively). In macroadenoma CD patients, HEX induced a slight, but significant increase (P < 0.02) in ACTH and F levels (33.9+/-18.0 pg/mL and 89.6+/-34.3 microg/L, respectively), which was not significantly different from that elicited by hCRH (20.0+/-7.0 pg/mL and 54.8+/-21.3 microg/L, respectively). In macroadenoma CD patients, the ACTH and F responses to HEX and hCRH were, in turn, similar to those in NS. In conclusion, our findings demonstrate that the ACTH and F hyperresponsiveness to HEX is present in Cushing's disease with micro-, but not macro- ACTH-secreting pituitary adenoma. This finding agrees with other evidence pointing toward differences in the hormonal behavior between micro- and ACTH-secreting pituitary macroadenomas.
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PMID:Adrenocorticotropin and cortisol hyperresponsiveness to hexarelin in patients with Cushing's disease bearing a pituitary microadenoma, but not in those with macroadenoma. 985 53

Ovarian steroids increase hypothalamic-pituitary-adrenal (HPA) axis activity and sensitize the hypothalamic-pituitary-ovarian (HPO) axis to stress-induced inhibition. The present study investigated the effect of ovarian steroids on CRH and arginine vasopressin (AVP) messenger RNA (mRNA) levels in the rhesus monkey hypothalamus, as both neuropeptides have been shown to stimulate the HPA axis and inhibit the HPO axis in this species. This was accomplished by measuring CRH and AVP mRNA in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) by in situ hybridization histochemistry. Menstrual cycles were simulated in ovariectomized (OVX) rhesus monkeys by sequential addition and removal of SILASTIC brand (Dow Corning Corp.) tubing containing either 17beta-estradiol (E2) or progesterone (P4). On the morning of day 11 of the simulated follicular phase (E2 alone) or day 21 of the luteal phase (E2 + P4), animals were anesthetized, and the brains were perfused with paraformaldehyde via the carotid artery. Coronal sections (30 microm) were cut, and mRNA for CRH and AVP in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) were semiquantified by in situ hybridization. CRH mRNA in the PVN of E2-replaced OVX animals (n = 7) was 2-fold greater than that in untreated OVX controls (n = 4), whereas CRH mRNA after E2 + P4 (n = 4) was no different from that in controls (optical density + SEM, 0.38 +/- 0.06, 0.13 +/- 0.08, and 0.14 +/- 0.09 for OVX + E2, OVX + E2 + P4, and OVX, respectively; P = 0.02). CRH in the SON was undetectable. In contrast to CRH, AVP mRNA in the PVN and the SON was similar in the three treatment groups. We conclude that E2 and E2 + P4 replacement to OVX monkeys exert different effects on CRH and AVP gene expression, as estrogen stimulation of CRH mRNA in the PVN was abrogated by progesterone, whereas no effect of ovarian steroids on AVP mRNA in either the PVN or SON was observed. We postulate that ovarian steroid regulation of CRH synthesis and release may in part explain the central nervous system mechanisms by which ovarian steroids affect the HPA and HPO axes during basal and stress conditions.
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PMID:The effects of estrogen and progesterone on corticotropin-releasing hormone and arginine vasopressin messenger ribonucleic acid levels in the paraventricular nucleus and supraoptic nucleus of the rhesus monkey. 1021 71


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