Adrenocorticotropic hormone and cortisol responses to corticotropin-releasing hormone: Changes in panic disorder and effects of alprazolam treatment

Objective: Adrenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome is biochemically characterized by increased plasma concentrations of ACTH inducing hypersecretion of cortisol. Somatostatin is known to inhibit ACTH secretion, and in vitro data have shown the inhibition of ACTH secretion by agonists activating sst2 and sst5 receptors. The present study aimed to determine the inhibitory effect of the multireceptor ligand SOM230, compared with the sst2-preferring agonist octreotide, on corticotropin-releasing hormone (CRH)-stimulated secretion of ACTH and corticosterone in rats. Methods: Secretion of ACTH and corticosterone was induced by i.v. application of CRH (0.5 μg/kg) in rats pretreated 1 h before by i.v. application of SOM230 (1, 3, or 10 μg/kg), octreotide (10 μg/kg) or NaCl 0.9%. Results: SOM230 (3 and 10 μg/kg) inhibited CRH-induced ACTH release by 45±3% and 51±2%, respectively, and corticosterone release by 43±5% and 27±16%, respectively. 10 μg/kg of octreotide tended to be less potent at inhibiting ACTH release (34±6% inhibition) and did not alter the secretion of corticosterone. Conclusion: SOM230 has a stronger inhibitory effect on ACTH and corticosterone secretion than octreotide in rats. This difference can be explained by its higher affinity to sst1, sst3 and especially sst5 receptors compared with octreotide.

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Possible role for corticotropin-releasing hormone in panic disorder

Journal of Psychiatric Research ◽

10.1016/0022-3956(90)90101-u ◽

1990 ◽

Vol 24 ◽

pp. 86-87 ◽

Cited By ~ 2

Author(s):

Phillip W. Gold

Keyword(s):

Panic Disorder ◽

Corticotropin Releasing Hormone ◽

Releasing Hormone

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Brain oxytocin receptors mediate corticotropin-releasing hormone-induced anorexia

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1991.260.2.r448 ◽

1991 ◽

Vol 260 (2) ◽

pp. R448-R452 ◽

Cited By ~ 13

Author(s):

B. R. Olson ◽

M. D. Drutarosky ◽

E. M. Stricker ◽

J. G. Verbalis

Keyword(s):

Food Intake ◽

Adrenocorticotropic Hormone ◽

Central Administration ◽

Corticotropin Releasing Hormone ◽

Releasing Hormone ◽

Oxytocin Receptors ◽

Artificial Cerebrospinal Fluid ◽

Pituitary Secretion ◽

Inhibit Food Intake ◽

Stimulation Of

Central administration of corticotropin-releasing hormone (CRH) is known to inhibit food intake and stimulate pituitary oxytocin (OT) secretion in rats. These experiments addressed the possibility that the inhibition of food intake that follows central CRH administration is mediated through oxytocinergic pathways. Male food-deprived rats, with stable baseline food intakes after intracerebroventricular (icv) injections of artificial cerebrospinal fluid, received 150 pmol of CRH icv. Food intake was inhibited by 62 +/- 5% during a 90-min test period. Pretreatment with 9 nmol of the OT antagonist [d(CH2)5, Tyr(Me)2, Orn8]vasotocin icv completely eliminated the inhibition of food intake produced by icv CRH. In contrast, pretreatment with the OT-receptor antagonist did not significantly alter pituitary secretion of adrenocorticotropic hormone and OT stimulated by icv CRH. The results of these experiments implicate OT as a possible central mediator of CRH-induced anorexias in rats, particularly those that are accompanied by stimulation of neurohypophysial OT secretion.

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Consistent Reduction of ACTH responses to stimulation with CRH, Vasopressin and Hypoglycaemia in Patients with Major Depression

The British Journal of Psychiatry ◽

10.1192/bjp.155.4.468 ◽

1989 ◽

Vol 155 (4) ◽

pp. 468-478 ◽

Cited By ~ 48

Author(s):

Roger G. Kathol ◽

Richard S. Jaeckle ◽

Juan F. Lopez ◽

William H. Meller

Keyword(s):

Major Depression ◽

Hpa Axis ◽

Negative Correlation ◽

Arginine Vasopressin ◽

Corticotropin Releasing Hormone ◽

Hypothalamic Pituitary Adrenal ◽

Releasing Hormone ◽

Control Subjects ◽

Basal Cortisol ◽

Cortisol Responses

Eleven patients with major depression and 12 control subjects were administered corticotropin-releasing hormone (CRH), aqueous arginine vasopressin (AVP), and insulin hypoglycaemia (IH) to test for differences in hypothalamic–pituitary–adrenal (HPA) axis function. Patients with major depression demonstrated lower ACTH responses to CRH when compared with controls, and a trend toward such after administration of AVP. Despite lower ACTH responses in patients with depression, there were no differences in Cortisol responses to these stimuli. In the CRH and AVP tests, there was no correlation between the basal Cortisol and ACTH responses in either controls or patients, but in the IH test there was a negative correlation between these responses for both groups. The ACTH responses to CRH and AVP were positively correlated in controls and patients. Cortisol responses to all three provocative stimuli were positively correlated in both subject groups. These findings are consistent with the hypothesis that hypothalamic or supra-hypothalamic overactivity may be involved in the development of HPA-axis abnormalities in patients with depression.

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