Corticotropin-releasing factor, a new aid in the diagnosis of pituitary-adrenal disorders?
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Adrenal Insufficiency↗
Biomedical subjects
A R Hermus
Publications and source records attributed to A R Hermus.
Differential effects of ovine and human corticotrophin-releasing factor in human subjects.
Ten healthy subjects received 200 micrograms of human CRF (hCRF) and 200 micrograms of ovine CRF (oCRF) as an intravenous bolus injection on two different occasions. After hCRF plasma ACTH levels rose significantly (P less than 0.0005, by Friedman's nonparametric analysis of variance) from a basal value of 35 +/- 3 pg/ml (mean +/- SEM) to a peak value of 80 +/- 7 pg/ml 30 min after hCRF administration. This ACTH response was followed by a rise in plasma cortisol levels (P less than 0.0005, by Friedman's test) from a baseline value of 0.32 +/- 0.03 mumol/l to a peak value of 0.56 +/- 0.02 mumol/l 60 min after hCRF. Ovine CRF elicited similar rises in the plasma ACTH and cortisol levels. However, as derived from the faster rate of decline of ACTH and cortisol after hCRF than after oCRF, human CRF had a significantly shorter duration of action than ovine CRF in humans. Human CRF not only stimulated ACTH release by the human pituitary gland but also prolactin release. After hCRF administration prolactin levels rose significantly (P less than 0.005, by Friedman's test) from a basal value of 179 +/- 18 mU/l to a peak value of 288 +/- 34 mU/l at 10 min.
Adolescent↗
Growth hormone responsiveness to human pancreatic growth hormone releasing factor in acromegaly: modulatory effects of basal hormone levels and of concomitant somatostatin administration.
Human pancreatic growth hormone releasing factor 1-44 (hpGRF), 100 micrograms was administered as an i.v. bolus injection to eleven patients with acromegaly. The mean serum growth hormone (GH) levels rose (P less than 0.001) from 54 +/- 20 ng/ml to 215 +/- 126 ng/ml (+/- SEM) 20 min after the injection. Although the maximum response of GH levels was highly variable it correlated positively with the individual GH levels (P less than 0.01, Rs = +0.80). Thus the higher the GH levels, the greater the responsiveness to hpGRF. Administration of somatostatin (SRIF), 300 micrograms/h, lowered basal GH levels from 76 +/- 38 ng/ml to 13 +/- 5 ng/ml (P less than 0.01) after 1 h. hpGRF administration during concomitant SRIF infusion also led to highly variable growth hormone responses. The maximum GH responses again correlated positively with the GH level before hpGRF after 1 h of SRIF administration (P less than 0.05, Rs = +0.79). GH responses to hpGRF were completely blocked by SRIF in three out of four patients whose GH levels decreased to normal levels during SRIF infusion. Our data illustrate that the pituitary in acromegaly is normally responsive to both SRIF and hpGRF but at a higher setting of basal GH levels.
Acromegaly↗
Plasma adrenocorticotropin, cortisol, and aldosterone responses to corticotropin-releasing factor: modulatory effect of basal cortisol levels.
Two hundred micrograms of corticotropin-releasing factor (CRF) were administered as an iv bolus injection to 10 normal subjects (5 men and 5 women). Mean plasma ACTH levels rose significantly (P less than 0.0005, by Friedman's nonparametric analysis of variance) from a basal value of 27 +/- 5 pg/ml (mean +/- SEM) to a peak value of 63 +/- 8 pg/ml 30 min after CRF administration. This ACTH response was followed by a rise in plasma mean cortisol levels (P less than 0.0005, by Friedman's test) from a baseline value of 12.3 +/- 1.4 micrograms/100 ml to a peak value of 21.0 +/- 0.7 micrograms/100 ml 60 min after CRF and a rise in mean plasma aldosterone levels from a basal value of 13 +/- 2 ng/100 ml to a peak value of 23 +/- 2 ng/100 ml. There was no significant difference between men and women in the responsiveness of ACTH, cortisol, and aldosterone to CRF administration. The individual basal cortisol levels were highly significantly and negatively correlated with the areas under the individual ACTH curves (r = -0.76; P less than 0.005, by Pearson's correlation test) and cortisol curves (r = -0.91; P less than 0.001, by Pearson's test). These data suggest a modulatory effect of physiological cortisol levels on the response of the pituitary-adrenal axis to CRF.
Adolescent↗
Differential effect of single high dose and divided small dose administration of human chorionic gonadotropin on Leydig cell steroidogenic desensitization.
This study compared the effect of a single high dose of hCG (1500 IU) with that of the same dose administered in multiple small doses (300 IU, once daily for 5 days) on Leydig cell steroidogenesis. Administration of a single high dose of hCG to seven healthy men raised the mean plasma testosterone (T) level to peak levels 2.1 +/- 0.2 (SEM) X the baseline value at 48 h. Thereafter plasma T decreased to below normal (0.7 +/- 0.1 X baseline) 7 days after the injection. The mean 17-hydroxyprogesterone (17-OHP) level peaked at 24 h (2.5 +/- 0.2 X baseline) and then also fell to a nadir value of 0.6 +/- 0.2 X baseline on day 7. Reflecting the early accumulation of 17-OHP over T, the 17 OHP/T ratio reached its maximum (1.6 +/- 0.1 X baseline) at 24 h at the same time when plasma estradiol [(E2) 4.4 +/- 0.6 X baseline] and the ratio E2/T (2.7 +/- 0.3 X baseline) achieved their maximal values. Administration of 1500 IU hCG in five divided doses of 300 IU daily increased the mean plasma T levels to peak value of 2.1 +/- 0.2 X baseline at 5 days and the levels remained elevated thereafter. The response of T as reflected by the area under the curve was almost twice as great as in the single dose study (2844 +/- 360 vs. 1647 +/- 214). In contrast to the single high dose experiment, mean plasma 17-OHP levels in the divided dose protocol did not peak at 24 h but only gradually increased. As the increase of T exceeded the 17-OHP increase at almost all time intervals, no accumulation of 17-OHP over T occurred as in the single dose experiment. Instead the 17-OHP/T ratio fell to a nadir value of 0.6 +/- 0.1 X baseline on day 7. The initial E2 peak was absent in the divided dose protocol and the E2/T ratio only marginally increased. Considering both experiments together a close relation was found between the hCG-induced increases in E2 and 17-OHP (r = +0.88, P less than 0.001), as well as the ratio 17 OHP/T (r = +0.64, P less than 0.02).(ABSTRACT TRUNCATED AT 400 WORDS)
17-alpha-Hydroxyprogesterone↗
Paradoxical responsiveness of growth hormone to corticotropin-releasing factor in acromegaly.
Corticotropin-releasing factor elicited an increase in serum GH in two of six patients with acromegaly. Both patients also responded paradoxically to LHRH administration and one of them also to TRH, further illustrating the dedifferentiation of the receptors of the somatotrophs in acromegaly.
Acromegaly↗
Responsiveness of the hypophyseal-adrenocortical axis to corticotropin-releasing factor in pituitary-dependent Cushing's disease.
Corticotropin-releasing factor [(CRF) 200 micrograms] was administered iv to five patients with classical pituitary-dependent Cushing's disease and to five normal subjects. In both groups no changes were observed in the plasma concentrations of hGH, PRL, TSH, LH, or FSH. In the normal subjects plasma ACTH levels rose from 41 +/- 9 (SEM) pg/ml to 87 +/- 28 pg/ml after 60 min (P less than 0.01) and plasma cortisol levels from 0.30 +/- 0.06 mumol/liter (8.0 +/- 0.2 micrograms/dl) to 0.53 +/- 0.07 mumol/liter (14.2 +/- 0.2 micrograms/dl) after 60 min (P less than 0.001). In the patients with classical Cushing's disease plasma ACTH levels increased from 109 +/- 23 to 281 +/- 78 pg/ml after 30 min (P less than 0.01) and plasma cortisol levels from 0.45 +/- 0.06 mumol/liter (12.0 +/- 0.2 micrograms/dl) to 1.02 +/- 0.21 mumol/liter (27.2 +/- 0.6 micrograms/dl) after 120 min (P less than 0.005). The absolute increments of ACTH and cortisol levels in the patients with Cushing's disease were significantly (P less than 0.02 and P less than 0.05, respectively) higher than in the normal subjects. In individual patients, however, CRF responses were rather variable; three of the patients had ACTH or cortisol increases within the mean +/- SD of the responses of the control subjects. In another patient with Cushing's disease due to bilateral macro- and micronodular adrenocortical hyperplasia, who had nonsuppressible circulating ACTH and cortisol levels, unresponsiveness to CRF was shown. These results indicate that testing the pituitary-adrenocortical axis of patients with Cushing's disease may reveal hyperresponsiveness, normal responsiveness, and even unresponsiveness.
Adrenal Cortex↗
Intravenous administration of interleukin-1 beta induces Fos-like immunoreactivity in corticotropin-releasing hormone neurons in the paraventricular hypothalamic nucleus of the rat.
It has been shown that acute administration of recombinant human interleukin 1 beta (IL-1) to rats elicits an activation of the pituitary-adrenal axis. In the present study we investigated immunohistochemically the expression of Fos-like immunoreactivity (Fos-LI) in the hypothalamus of rats following intravenous injection of IL-1. One, 2 and 4 h after IL-1 or physiological saline injections, rats were killed and perfused, and the brains processed for Fos-immunohistochemistry. Dense populations of neurons containing Fos-LI-positive nuclei were found in the paraventricular hypothalamic nuclei (PVH) of IL-1-treated rats. In particular, the dorsal medial parvocellular part, but also some of the other parvocellular subdivisions contained many Fos-LI neurons. Maximal induction of staining was found at a dose of 5 micrograms/rat after 1 or 2 h survival, while immunostaining had decreased to almost control levels after 4 h. No Fos-LI was found in the PVH of control animals. Double immunocytochemical staining for Fos and corticotropin-releasing hormone (CRH) revealed that Fos-LI was predominantly present in parvocellular CRH-containing neurons of the PVH. The finding that peripherally injected IL-1 induces Fos-LI in hypothalamic CRH neurons strengthens the hypothesis that these neurons are part of the circuitry mediating IL-1-induced activation of the pituitary-adrenal axis.
Adrenocorticotropic Hormone↗
Reduced adrenal response and increased mortality after systemic Klebsiella pneumoniae infection in interleukin-6-deficient mice.
During bacterial infections, both the immune system and the hypothalamus-pituitary-adrenal (HPA) axis are activated. The role of IL-6 in the activation of the HPA axis during bacterial sepsis is not fully understood. The aim of the present study was to investigate the role of endogenous IL-6 in a potentially lethal infection with Klebsiella pneumoniae and the concomitant activation of the HPA axis. We examined the mortality of IL-6-/- and IL-6+/+ mice after intravenous (i.v.) infection with K. pneumoniae as well as the bacterial outgrowth in several organs. Subsequently, the influence of endogenous IL-6 on the effect of i.v. administration of K. pneumoniae on the plasma levels of corticosterone and the pro-inflammatory cytokines TNF-alpha and IL-1alpha was investigated in these mice. The present study demonstrates that IL-6-/- mice are more susceptible than IL-6+/+ mice to a systemic Gram-negative infection with K. pneumoniae, leading to increased outgrowth of microorganisms in the organs of the mice. Moreover, this infection is associated with a reduced adrenal response in IL-6-/- mice. We conclude that IL-6-/- mice are more susceptible to Gram-negative bacterial infections, which is mainly due to an impaired recruitment of granulocytes to the site of infection in the absence of IL-6. Furthermore, the reduced adrenal response may be an explanation for the strong inflammatory response with higher TNF-alpha plasma levels in IL-6-/- mice.
Adrenal Glands↗
Pancreatic islet cell tumor producing vasoactive intestinal polypeptide and calcitonin.
A patient with a pancreatic islet cell tumor concurrently producing vasoactive intestinal polypeptide (VIP) and calcitonin with related symptoms is presented. The patient was given palliative treatment consisting of octreotide, streptozotocin and 5-fluorouracil, and survival now exceeds 72 months. The concurrent production of VIP and calcitonin by a pancreatic islet cell tumor has not been described before.
Antineoplastic Combined Chemotherapy Protocols↗