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At least 109 records · Page 6Linked to original sources
PubMed1978

In vitro release of ACTH from dispersed rat pars intermedia cells. III. Multiple forms of ACTH biological activity.

We have reported that both an extract of rat hypothalamus-stalk-median eminence (HE) and 5-hydroxytryptamine (5-HT) will stimulate the release of ACTH biological activity from acutely, non-enzymically dispersed rat pars intermedia (PI) cells. We have also found that the ACTH activity within the PI cells is composed of 4 chromatographically separable entities, but only a small proportion of the total ACTH activity co-elutes with ACTH1-39. In the present study we subjected the media, after incubation of PI cells with either HE or 5-HT, to sequential chromatography on Sephadex G-50 F and G-100 SF. We found the same 4 ACTH-like moieties as in the PI cell extracts. Only the release of the 2 earliest eluting components, presumably of much larger molecular dimensions than ACTH1-39, was enhanced by either HE or 5-HT. There was no augmented release of the ACTH component having molecular dimensions similar to ACTH1-39. Thus, in our in vitro system, the ACTH biological activity released from PI cells is not the size of ACTH1-39, but is composed of at least 2 much larger molecules which possess ACTH (as well as some MSH) biological activity.

Adrenocorticotropic Hormone↗
PubMed1981

Adrenocortical sensitivity to adrenocorticotropin (ACTH) in awake dogs changes as a function of the time of observation and after hemorrhage independently of changes in ACTH.

Adrenocortical sensitivity to ACTH, defined as the slope of the log dose-response curve, was determined in awake dogs by measuring cortisol secretory rates after graded doses of ACTH. Adrenocortical sensitivity varied as a function of the time of observation. The AM sensitivity was greater than the PM sensitivity in the absence of an AM-PM difference in basal plasma ACTH. Additionally, sensitivity was increased in the PM 6--8 h after moderate hemorrhage in the AM. However, exogenous ACTH given in the AM did not augment adrenal sensitivity to ACTH in the PM. These data show that adrenocortical sensitivity to ACTH varies in awake dogs and that the changes in sensitivity cannot be completely accounted for by changes in ACTH.

Adrenal Cortex↗
PubMed1990

Treatment of primary cultures of calf adrenal glomerulosa cells with adrenocorticotropin (ACTH) and phorbol esters: a comparative study of the effects on aldosterone production and ACTH signaling system.

We studied the mechanism that underlies the desensitization of calf adrenal glomerulosa cells induced by 4 h of ACTH treatment. In control cells, acute ACTH treatment provoked sizeable increases in aldosterone, cAMP, and diacylglycerol, and translocated protein kinase-C from cytosol to membrane. In desensitized cells, acute ACTH effects on aldosterone and cAMP decreased by 25-60%, and diacylglycerol levels and protein kinase-C translocation were persistently stimulated and not substantially affected by further acute ACTH treatment. After 4 h of treatment with 1 microM phorbol 12-myristate 13-acetate (PMA) there were no acute effects of ACTH on the production of aldosterone, cAMP, or diacylglycerol or on protein kinase-C, which was already strongly translocated. These results suggest that ACTH-mediated desensitization of calf adrenal glomerulosa cells may be at least partially mimicked by long term treatment with phorbol esters and could be due to ACTH-induced increases in diacylglycerol-protein kinase-C signaling.

Adrenal Glands↗
PubMed2004

Characterization of an adrenocorticotropin (ACTH) receptor promoter polymorphism leading to decreased adrenal responsiveness to ACTH.

The ACTH receptor has a pivotal role in the regulation of adrenal cortisol secretion. Here, we describe a polymorphism within the transcription initiation site of the ACTH receptor promoter altering the consensus sequence from CTC to CCC. The prevalence of the polymorphism in 1266 unrelated healthy men was 80.2% for CTC/CTC, 19.0% for CTC/CCC, and 0.8% for CCC/CCC, respectively. In vitro studies using luciferase assays demonstrated a lower basal (CCC, 73 +/- 4%; CTC, 100 +/- 5%; P = 0.02) and forskolin-stimulated (CCC, 143 +/- 13%; CTC, 194 +/- 15%; P = 0.0008) promoter activity in the CCC construct compared with CTC. The clinical significance of the in vitro findings was investigated by a 6-h ACTH stimulation test with increasing ACTH(1-24) doses in normal subjects, demonstrating a blunted cortisol response in CCC/CCC subjects compared with CTC/CTC individuals (area under the curve, 12176 +/- 966; 16334 +/- 1051 nmol/liter.min; P < 0.03). Accordingly, after CRH stimulation, subjects with CCC/CCC showed a higher ACTH/cortisol ratio (P < 0.05) suggesting a decreased adrenal responsiveness to endogenous ACTH. In conclusion, we describe an ACTH receptor promoter polymorphism that results in a lower promoter activity in vitro and is associated with a lower cortisol secretion to prolonged ACTH stimulation in vivo. This polymorphism might influence cortisol homeostasis under stress conditions.

Adrenal Glands↗
PubMed1982

Effects of a met-enkephalin analog on adrenocorticotropin (ACTH), growth hormone, and prolactin in patients with ACTH hypersecretion.

The effect of D-Ala2, MePhe4, Met-(0)enkephalinol (Sandoz FK 33-824; 0.5 mg, im) on pituitary hormone secretion was studied in 11 patients with Addison's disease and 11 patients with ACTH-dependent Cushing's disease. In patients with Addison's disease, a pronounced fall of plasma ACTH levels was observed (P less than 0.005). The ACTH response to FK 33--824 was partially reversed by naloxone (4 mg, iv). In patients with Cushing's disease, no unequivocal decrease in either ACTH or cortisol was seen. Moreover, FK 33--824 failed to influence the vasopressin-induced ACTH increase in 5 patients with Cushing's disease. In patients with cortisol deficiency due to either Addison's disease or bilateral adrenalectomy for Cushing's disease, FK 33--824 led to increases in PRL and GH similar to those described in normal subjects. However, in the presence of longstanding hypercortisolism, the PRL increase was significantly diminished, and the GH response to FK 33--824 was completely abolished. Our results suggest that in Addison's disease ACTH release is influenced by inhibitory opiate receptors. In patients with Cushing's disease, ACTH secretion is insensitive to FK 33-284, presumably because of an autonomous pituitary adenoma or hypothalamic derangement. The impairment of the PRL and GH responses to FK 33--824 in Cushing's syndrome seems to reflect a direct action of the elevated cortisol level, for it is not seen after bilateral adrenalectomy.

Addison Disease↗
PubMed1987

Pulsatile rhythms of adrenocorticotropin (ACTH) and cortisol in women with endogenous depression: evidence for increased ACTH pulse frequency.

Plasma ACTH and serum cortisol levels were measured at 20-min intervals for 24 h in six young women with unipolar endogenous depression and in eight normal women during the early follicular phase of the menstrual cycle. The women with depression had a marked increase (P less than 0.005) in mean ACTH pulse frequency [14.5 +/- 0.6 (+/-SE) pulses/24 h] compared with normal women (9.9 +/- 0.7 pulses/24 h), while mean ACTH pulse amplitude and 24-h transverse mean ACTH levels were similar in the two groups. In contrast, 24-h transverse mean cortisol levels were higher (P less than 0.02) in the depressed women (242 +/- 28 nmol/L) than in the normal women (163 +/- 10 nmol/L). This hypercortisolemia in the depressed women was accompanied by markedly increased (P less than 0.001) episodic cortisol secretion (286 +/- 24 X 10(2) nmol/L X min) compared with that in normal women (155 +/- 17 X 10(2) nmol/L X min), and the secretory episodes were both longer in duration (P less than 0.05) and of higher amplitude (P less than 0.05) in the depressed women. The circadian variations in ACTH and cortisol were maintained in these depressed women, and the times of the circadian nadir, as determined by cosinor analysis, were similar to those in the normal women. However, the mean length of the evening quiescent period of cortisol secretion was far shorter (P less than 0.005) in the depressed women (27 +/- 8 vs. 202 +/- 40 min). Moreover, the postlunch rise in serum cortisol was significantly higher (P less than 0.02) in the depressed women (204 +/- 29 vs. 111 +/- 15 nmol/L). These results provide evidence that the hypercortisolism in depressed women is associated with an increase in ACTH pulse frequency, expanded cortisol secretory episodes, including a greater postlunch rise in cortisol, and a shortened evening quiescent period of cortisol secretion. Our findings provide evidence for centrally mediated activation of the ACTH-cortisol system in women with depression without a phase shift in circadian rhythm.

Adrenocorticotropic Hormone↗
PubMed2005

Co-localization of honeycomb golgi and ACTH granules in a giant ACTH-producing pituitary adenoma.

We document the co-localization of honeycomb golgi and ACTH-immunopositive granules in giant ACTH-producing pituitary adenoma cells. A 42-yr-old woman presented with Cushing's disease and a giant adenoma that invaded the sphenoid and cavernous sinus. She underwent transsphenoidal surgery followed by radiation therapy. Some of the adenoma cells were ACTH-positive and upon electron-microscopic (EM) study most were found to contain sparse granules and no type-I filaments. In many cells the golgi complex had undergone partial or total vacuolar transformation that resulted in the appearance of honeycomb golgi. Immunohistochemical study of mirror sections of portions containing cells with honeycomb golgi revealed that the cells with honeycomb golgi showed ACTH-immunopositivity. Honeycomb golgi, which was formerly considered a morphological marker of gonadotroph adenomas in females, has previously been identified in large ACTH-producing pituitary adenomas but there has been no direct evidence that individual cells with honeycomb golgi are cells that produce ACTH. Our immunohistochemical documentation of ACTH-immunoreactivity in individual adenoma cells containing honeycomb golgi clearly confirms that honeycomb golgi is not confined only to gonadotroph adenomas in females. Rather, the existence of honeycomb golgi in cells of other adenoma types may be due to their low hormone production and/or to disturbances in the regulation of the exocytotic pathway.

Adenoma↗
PubMed1989

Reports of two cases of selective adrenocorticotropin (ACTH) and growth hormone (GH) deficiency: differential diagnosis from cases with isolated ACTH deficiency associated with transient GH insufficiency.

An acquired partial pituitary insufficiency with selective ACTH and GH deficiency was demonstrated in two men aged 47 and 54, for which the clinical course over many years corresponds to Addison's disease. In one of the 2 cases, antibodies to anterior pituitary cell membrane, assayed by an immunofluorescence method with GH3 cells (rat GH and prolactin secreting cell) and AtT-20 cells (mouse ACTH secreting cell) as antigens, were positive. We also present a 55-year-old man with isolated ACTH deficiency associated with transient GH deficiency. In this case, hydrocortisone replacement corrected his subnormal, pre-therapy GH response to insulin tolerance and glucagon propranolol tests, although there was no response of serum GH to L-dops and arginine stimulation test before therapy. Selective ACTH and GH deficiency are very rare and the finding of transient GH insufficiency in a patient with isolated ACTH deficiency suggests that repeated testing while on hydrocortisone replacement therapy is of great diagnostic importance in order to distinguish between selective ACTH and GH deficiency and isolated ACTH deficiency accompanied by transient GH insufficiency.

Adrenocorticotropic Hormone↗
PubMed1987

Effects of ACTH and ACTH fragments on DNA synthesis in guinea-pig adrenal segments kept in organ culture.

Stimulation of adrenal DNA synthesis by ACTH and its fragments ACTH (Synacthen) and ACTH was investigated. Synthesis of DNA was measured as the increase in the percentage of cells in S-phase (Feulgen densitometry) in guinea-pig adrenal explants kept in organ culture and exposed to the peptides for 5 h at 37 degrees C. ACTH and its C-terminal fragment ACTH (corticotrophin-like intermediate lobe peptide) were found to be potent stimulators of in-vitro adrenal DNA synthesis. The dose-response kinetics were biphasic and optimal responsiveness was reached in both instances at 1 fmol/1-10 pmol/1 (this biological effect of ACTH has hitherto not been described). The N-terminal fragment ACTH gave only minimal responses. Thyrotrophin and LH, tested as controls, did not induce adrenal DNA synthesis. Epidermal growth factor was a potent stimulator of adrenal DNA synthesis in vitro. Our data suggest a trophic action of the C-terminal part of the corticotrophic molecule. Clear trophic effects were also found for the N-terminal part of the pro-opiomelanocortin molecule N-POC (optimum 0.1 nmol/l) and N-POC(51-62) (optimum 0.1 pmol/l). The latter observations support earlier concepts that this part of the pro-opiomelanocortin molecule has a stimulatory effect on adrenal DNA synthesis.

Adrenal Cortex↗
PubMed1987

Plasma endogenous ACTH concentrations and plasma cortisol responses to synthetic ACTH and dexamethasone sodium phosphate in healthy cats.

Plasma cortisol responses of 19 healthy cats to synthetic ACTH and dexamethasone sodium phosphate (DSP) were evaluated. After administration of 0.125 mg (n = 5) or 0.25 mg (n = 6) of synthetic ACTH, IM, mean plasma cortisol concentrations increased significantly (P less than 0.05) at 15 minutes, reached a peak at 30 minutes, and decreased progressively to base-line values by 120 minutes. There was no significant difference (P greater than 0.05) between responses resulting from the 2 dosage rates. After administration of 1 mg of DSP/kg of body weight, IV (n = 7), mean plasma cortisol concentrations decreased at postadministration hour (PAH) 1, and were significantly lower than control cortisol concentrations at PAH 4, 6, 8, 10, and 12 (P less than 0.01). Administration of 0.1 mg of DSP/kg, IV (n = 8) or 0.01 mg of DSP/kg, IV (n = 14) induced results that were similar, but less consistent than those after the 1 mg of DSP/kg dosage. Mean plasma cortisol concentrations returned to base-line values by PAH 24. There was not a significant difference between the 3 doses (P greater than 0.05) at most times. Measurement of endogenous ACTH in 16 healthy cats revealed plasma ACTH of less than 20 to 61 pg/ml. Seemingly, administration of synthetic ACTH consistently induced a significant (P less than 0.05) adrenocortical response in healthy cats. On the basis of time-response studies, post-ACTH stimulation cortisol samples should be collected at 30 minutes after ACTH administration to ensure detection of peak adrenocortical response.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Function Tests↗
PubMed1980

[Therapeutic trial with a fragment of ACTH (ACTH 4-10) in early childhood epilepsy (author's transl)].

Epilepsy in early childhood has been treated successfully with ACTH. However, side effects were significant due to the stimulation of the adrenal cortex by high doses of ACTH over a long time. It has been suggested, that ACTH does not influence the seizures via the adrenal cortex. Therefore we administered an ACTH fragment (ACTH 4-10) which does not influence the adrenal cortex. Seven children aged between 8 months and 13 1/2 years were treated at least for 3 weeks with doses from 15 mg twice daily to 12 x 30 mg/day. Adrenal stimulation did not occur as proven by normal circadian plasma cortisol levels. However, the EEG regularly repeated, did not show improvements. The frequency of seizure was not reduced. It is concluded that this ACTH fragment (ACTH 4-10) does neither influence the adrenal cortex nor the EEG nor the frequency of seizures in early childhood epilepsy.

Adolescent↗
PubMed1986

Diagnosis and management of ACTH-dependent Cushing's syndrome: comparison of the features in ectopic and pituitary ACTH production.

The clinical features, diagnosis and management of 16 consecutive patients with ectopic ACTH production are described and biochemical data are compared with those of 48 consecutive patients with pituitary-dependent Cushing's disease. In 10 cases the ectopic ACTH secreting tumour was completely occult to routine clinical and radiological investigation, and no basal or dynamic investigation of adrenal-pituitary function was able clearly to differentiate these patients from those with Cushing's disease. High dose dexamethasone suppression testing assessed by plasma cortisol was usually helpful but unexpected responses were seen in both diagnostic groups; the metyrapone test yielded no useful information and should now be abandoned. Hypokalaemia was seen in all patients with ectopic ACTH production but in only 10% of those with Cushing's disease who were not on diuretics at presentation. Successful diagnosis and tumour localization was most frequently achieved by a combination of CT scanning of the chest and abdomen and venous catheter sampling for ACTH. All patients in whom the ectopic ACTH-secreting tumour was obvious at presentation died of their primary tumour within 8 months, whereas seven of the 10 patients with occult tumours at presentation are alive 1.5-16.5 years later, and appear cured. Occult ectopic ACTH secretion may be impossible to distinguish from pituitary Cushing's disease. Multiple and repeated investigations are often required to make this differential diagnosis, essential for appropriate therapy.

ACTH Syndrome, Ectopic↗