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Biomedical subjects

O A Müller

Publications and source records attributed to O A Müller.

At least 73 records · Page 4Linked to original sources
PubMed1988

Methodological aspects of hCRF-stimulated ACTH and cortisol secretion in healthy subjects.

This study, aimed at clarifying some methodological problems of the hCRF stimulation test, was performed on 12 healthy male volunteers. ACTH and cortisol increases after 30 min and their maximum increase proved to be highly reliable response parameters for the net area under the response curve of both hormones. An influence of baseline hormone values on the maximum response was apparent for cortisol but not for ACTH. Cortisol, but not ACTH, revealed a stable test-retest reliability. There were no correlations between ACTH and cortisol responses to hCRF.

Adrenocorticotropic Hormone↗
PubMed1988

Insulin hypoglycemia test and releasing hormone (corticotropin-releasing hormone and growth hormone-releasing hormone) stimulation in patients with pituitary failure of different origin.

To investigate the efficacy of endocrine evaluation in diagnosing and localizing the cause of anterior pituitary failure, 17 patients with suprasellar space-occupying lesions, 4 patients with intrasellar tumors, 8 patients with no detectable anatomical lesion, 1 patient with posttraumatic failure and 1 patient with septooptical dysplasia were investigated. Endocrine evaluation consisted of measuring adrenocorticotropic hormone (ACTH), cortisol, and growth hormone (GH) levels during insulin hypoglycemia test (IHT) and after administration of corticotropin-releasing hormone (CRH) and growth hormone-releasing hormone (GRH). In addition, basal prolactin levels, gonadal and thyroid function were evaluated. The results showed that 4 of 17 patients with suprasellar tumors had normal ACTH and GH responses during IHT and after releasing hormone (RH) administration. Five of these patients had a normal ACTH or cortisol rise but no GH response during IHT. All 5 had a normal ACTH and 3 had normal GH rise after RH. Seven patients with suprasellar tumors had no ACTH or GH response during IHT, but all had an ACTH response to CRH. Only 3 of this group had a GH response to GRH. There was one exception of a patient who showed a GH and ACTH rise during IHT but only a blunted ACTH and no GH rise after RH administration. Four patients with pituitary failure and no demonstrable lesion had an ACTH rise after CRH but no GH rise after GRH, whereas in 3 patients with isolated ACTH deficiency no ACTH rise after CRH was seen. In 4 patients with nonsecreting pituitary tumors normal ACTH responses to IHT and CRH were seen, whereas GH rose during IHT only in 1 patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Ketoconazole inhibits corticotropic cell function in vitro.

The effects of ketoconazole (KC) on secretion and biosynthesis of ACTH and generation of cAMP in rat anterior pituitary cells were investigated in vitro. KC inhibits CRF-stimulated ACTH release from rat anterior pituitary fragments in a dose-dependent fashion between 1.5 and 100 microM. The effect of CRF as a releaser of ACTH was fully restored after KC was removed from the medium. Similar effects were observed in primary cultures of rat anterior pituitary cells. KC dose-dependently decreased basal and CRF-stimulated ACTH release. In addition, basal and CRF-stimulated mRNA coding for the ACTH precursor were reduced after preincubation with KC. The effects of KC on ACTH release and biosynthesis seem to be mediated by cAMP, since KC inhibits basal and CRF-stimulated cAMP release and content within the same dose range. Since the stimulatory effects of cholera toxin, sodium fluoride, and forskolin were dose-dependently inhibited by KC and since the addition of (Bu)2cAMP abolished the inhibiting effect of KC, it is concluded that KC acts by inhibition of the catalytic component of the adenylate cyclase holoenzyme.

1-Methyl-3-isobutylxanthine↗
PubMed1988

Arginine stimulates growth hormone secretion by suppressing endogenous somatostatin secretion.

To determine how arginine (Arg) stimulates GH secretion, we investigated its interaction with GHRH in vivo and in vitro. Six normal men were studied on four occasions: 1) Arg-TRH, 30 g arginine were administered in 500 mL saline in 30 min, followed by an injection of 200 micrograms TRH; 2) GHRH-Arg-TRH, 100 micrograms GHRH-(1-44) were given iv as a bolus immediately before the Arg infusion, followed by 200 micrograms TRH, iv; 3) GHRH test, 100 micrograms GHRH were given as an iv bolus; and 4) TRH test, 200 micrograms TRH were given iv as a bolus dose. Blood samples were collected at 15-min intervals for 30 min before and 120 min after the start of each infusion. Anterior pituitary cells from rats were coincubated with Arg (3, 6, 15, 30, and 60 mg/mL) and GHRH (0.05, 1, 5, and 10 nmol/L) for a period of 3 h. Rat GH was measured in the medium. After Arg-TRH the mean serum GH concentration increased significantly from 0.6 to 23.3 +/- 7.3 (+/- SE) micrograms/L at 60 min. TRH increased serum TSH and PRL significantly (maximum TSH, 11.1 +/- 1.8 mU/L; maximum PRL, 74.6 +/- 8.4 micrograms/L). After GHRH-Arg-TRH, the maximal serum GH level was significantly higher (72.7 +/- 13.4 micrograms/L) than that after Arg-TRH alone, whereas serum TSH and PRL increased to comparable levels (TSH, 10.2 +/- 3.0 mU/L; PRL, 64.4 +/- 13.6 micrograms/L). GHRH alone increased serum GH to 44.9 +/- 9.8 micrograms/L, significantly less than when GHRH, Arg, and TRH were given. TRH alone increased serum TSH to 6.6 +/- 0.6 mU/L, significantly less than the TSH response to Arg-TRH. The PRL increase after TRH only also was lower (47.2 +/- 6.8 micrograms/L) than the PRL response after Arg-TRH. In vitro Arg had no effect on basal and GHRH-stimulated GH secretion. Our results indicate that Arg administered with GHRH led to higher serum GH levels than did a maximally stimulatory dose of GHRH or Arg alone. The serum TSH response to Arg-TRH also was greater than that to TRH alone. We conclude that the stimulatory effects of Arg are mediated by suppression of endogenous somatostatin secretion.

Adult↗
PubMed1987

Potentiation of the hCRF-induced release of ACTH in man by an opioid antagonist.

Administration of synthetic human corticotropin-releasing factor (hCRF; 2 micrograms/kg body weight) to six normal male subjects produced a significant rise in plasma ACTH, followed by an increase in circulating cortisol. Simultaneous treatment with the opioid antagonist naloxone (1.6 mg i.v. bolus, followed by an infusion at a rate of 1.2 mg/h) significantly potentiated the hCRF-induced rise in ACTH and enhanced the cortisol response to hCRF. It is suggested that naloxone acts by antagonizing an inhibitory ultra-short-loop feedback effect of coreleased beta-endorphin on pituitary corticotrophs, thereby amplifying the net effect of hCRF, i.e., the release of ACTH.

Adrenocorticotropic Hormone↗
PubMed1987

Corticotropin-releasing factor in humans. II. CRF stimulation in patients with diseases of the hypothalamo-pituitary-adrenal axis.

A stimulation test with 100 micrograms ovine or human corticotropin-releasing factor (CRF) is a useful diagnostic tool in diseases of the hypothalamo-pituitary-adrenal axis. No serious side effects were observed during the test procedure. The results showed that the CRF test is useful in making the differential diagnosis of established Cushing's syndrome (n = 42). The CRF test was also repeated after transsphenoidal surgery in 25 patients with Cushing's disease. Successfully operated patients exhibit no, blunted or normal adrenocorticotropic hormone (ACTH) responses to CRF (n = 15), whereas patients who did not show remission remained hyperresponsive (n = 10). In patients with autonomous adrenal cortisol secretion, the ACTH response to CRF was suppressed (n = 10). After surgery the ACTH response to CRF can already be demonstrated when cortisol levels are still undetectable. Pulsatile administration of CRF in one patient after unilateral adrenalectomy and another patient under corticoid therapy revealed that ACTH responses to CRF normalize rapidly but cannot be sustained if CRF administration is withdrawn, suggesting that the cause of adrenal failure after unilateral adrenalectomy for Cushing's syndrome or long-term corticoid therapy is due to hypothalamic CRF deficiency. The decrease of the ACTH responses to CRF in glucocorticoid-treated patients correlated directly to the daily corticoid dosage. Since the ACTH hyperresponse to CRF in 6 patients with Cushing's disease was also suppressed by short-term dexamethasone treatment, the pituitary level as target site for the acute feedback inhibition is also demonstrated. The evaluation of the CRF-induced ACTH response in patients with secondary adrenal failure without detectable pathology in the sella and suprasellar region (n = 6) enables the differentiation between hypothalamic and pituitary adrenal insufficiency. In patients with hypothalamic lesions the ACTH response to CRF was normal whereas insulin hypoglycemia failed to induce an ACTH rise.

Adrenal Gland Diseases↗
PubMed1987

Corticotropin-releasing hormone stimulation test before and after transsphenoidal selective microadenomectomy in 30 patients with Cushing's disease.

Thirty patients with ACTH-dependent Cushing's disease were tested with CRH before and 7-10 days and 3-6 months after selective transsphenoidal adenomectomy. In 28 of 30 patients an adenoma was found, and in 22 (79%) clinical and endocrinological remission occurred. Preoperatively, the majority of the patients had basal and CRH-stimulated plasma ACTH levels that were markedly increased compared to those in normal subjects. On the basis of the CRH stimulation test and low dose (2 mg) dexamethasone suppression test results 7-10 days after surgery, these 30 patients were divided into 4 groups. Groups I, II, and III were patients in remission, as defined by undetectable, subnormal, or normal basal plasma ACTH and cortisol levels in addition to sufficient suppression of cortisol (less than 2 micrograms/dL) during the low dose (2 mg) dexamethasone suppression test. Patients in group IV were not in remission. In group I (n = 6), CRH failed to raise undetectable basal ACTH levels in the early postoperative period; however, 3-6 months later plasma ACTH did increase in response to CRH. In group II (n = 11), undetectable or low basal ACTH levels increased after CRH, and the increase was similar to that in normal individuals. In group III (n = 5), basal ACTH levels were normal, and the response to CRH was exaggerated, but all patients responded normally to the dexamethasone suppression test. The CRH-induced ACTH increase in group III was significantly greater (P less than 0.003) than that in normal subjects, but was similar to that in patients not in remission in group IV (n = 6). Three to 6 months later, the ACTH response to CRH in group III was normal. In summary, the CRH test 7-10 days after surgery in patients with Cushing's disease indicated remission when there was no CRH-induced ACTH response or the response was normal (groups I and II). The test failed to predict remission in patients with an exaggerated CRH-induced ACTH response (groups III and IV). However, with regard to group II, the CRH-induced ACTH increase 1 week after selective adenomectomy indirectly supports the concept of CRH deficiency during hypercorticism and thus, in these patients as well as in group I, a pituitary origin of the disease.

Adenoma↗
PubMed1987

Pharmacological modulation of CRH-stimulated ACTH secretion by ketoconazole.

The effects of ketoconazole (KC) on secretion and biosynthesis of ACTH in rat anterior pituitary cells were investigated in vitro. KC inhibits the corticotropin releasing hormone (CRH) stimulated ACTH release from rat anterior pituitary fragments in a dose dependent fashion between 1.5 and 100 microM. The effect of CRH to release ACTH was fully restored after KC was removed from the medium. Similar effects were observed in primary cultures of rat anterior pituitary cells: KC decreased dose dependently the basal and CRH stimulated ACTH release. In addition, basal and CRH-stimulated mRNA coding for the ACTH precursor was reduced after preincubation with CK. The effects of KC on ACTH release and biosynthesis seems to be mediated by cyclic AMP (cAMP) since KC inhibits basal and CRH stimulated cAMP release and content within the same dose range. Since the stimulatory effect of cholera toxin, sodium fluoride and forskolin were dose dependently inhibited by KC and since the addition of dibutyryl cAMP abolished the inhibiting effect of KC, it is concluded that KC acts by inhibition of the catalytic component of the adenylate cyclase holoenzyme.

1-Methyl-3-isobutylxanthine↗
PubMed1987

CRH in Cushing's syndrome.

CRH-stimulation-test with 100 micrograms ovine or human corticotropin releasing hormone is useful in making the differential diagnosis of established Cushing's syndrome (N = 45). Only in 3 patients we did not find the expected result. In one patient with proven pituitary ACTH-dependent Cushing's disease there was no ACTH- and cortisol-increase after CRH-stimulation, whereas in two patients with ectopic ACTH-production due to a lung tumour there was a significant ACTH-increase after CRH-stimulation. The CRH-test was repeated 7-10 days after transsphenoidal surgery in 30 patients with Cushing's disease. Successfully operated patients exhibit no, blunted or normal ACTH responses to CRH. In patients with autonomous adrenal cortisol secretion after surgery the ACTH response to CRH can already be demonstrated when cortisol levels are still undetectable. The same could be shown for patients after long-term corticoid therapy suggesting that the cause of adrenal failure after unilateral adrenalectomy for Cushing's syndrome or long-term corticoid therapy is due to hypothalamic CRH deficiency. Acute administration of corticoids suppressed CRH-induced ACTH-secretion in normals and patients with pituitary ACTH-dependent Cushing's disease suggesting the pituitary level as target side for the acute feedback inhibition. Our results with different stimuli of the ACTH-secretion in normal controls (N = 6) with and without intravenous dexamethasone administration indicate a multihormonal control of pituitary adrenal activity.--Measurements of CRH-levels with a homologous human CRH-radioimmunoassay in patients with pituitary ACTH-dependent Cushing's disease did not help in differentiating these patients according to their possible pathophysiology (functional hypothalamic or autonomous pituitary cause of ACTH-hypersecretion).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1987

CRH test after pituitary microsurgery suggests tertiary adrenocortical insufficiency in successful operated patients with Cushing's disease.

In this study 30 patients with ACTH-dependent Cushing's disease underwent CRH-stimulation test before, 7-10 days and 3-6 months later after transphenoidal selective microadenomectomy. In 22 of 30 patients clinical and endocrinological remission (2 mg dexamethasone suppression test below 2 micrograms/dl cortisol) occurred. Fourteen of the 22 patients in remission showed a statistically significant increase of ACTH after CRH, 1 week after the operation. This CRH-induced ACTH increase in the early post-operative period gives indirect evidence for endogenous CRH deficiency and suggests tertiary adrenocortical insufficiency in successfully operated patients.

Adenoma↗
PubMed1986

Combined pituitary function-test with four hypothalamic releasing hormones.

Anterior pituitary function was investigated in ten healthy subjects by administering a combination of 200 micrograms thyrotropin releasing hormone (TRH), 100 micrograms gonadotropin releasing hormone (GnRH), 100 micrograms growth hormone releasing factor (GRF1-44), and 100 micrograms human corticotropin releasing factor (CRF). The same test protocol was performed in all subjects after pretreatment with 0.25 mg terguride. Five subjects were tested only with TRH and GnRH, five only with CRF, and six only with GRF. There was a prompt increase in all hormones after the administration of the four releasing hormones (RH). Pretreatment with terguride lowered the prolactin (PRL) increase (p less than 0.01) as well as the thyrotropin (TSH) peak (p less than 0.05) compared with the test without dopamine agonist pretreatment. The PRL levels after combined RH administration were significantly higher than after TRH and GnRH alone. Although four of the five subjects had higher TSH levels after combined RH administration than after TRH and GnRH alone, the difference was not significant. Other hormones were not significantly influenced by the combined RH administration or dopamine agonist pretreatment. Despite the fact that the interaction of the different releasing hormones and dopamine agonists influences the pituitary hormone response, combined RH administration seems to be a useful test for evaluating pituitary function also in patients receiving dopamine agonist therapy.

Adrenocorticotropic Hormone↗