Corticotrophin releasing hormone (CRH1–41) stimulates the secretion of adrenocorticotrophin, vasopressin and oxytocin but not adrenocorticotrophin precursors: evidence from petrosal sinus sampling in man

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Abstract
SUMMARY: To examine the relationship between corticotrophin releasing hormone (CRH), arginine vasopressin (AVP) and oxytocin (OXT) we have studied the responses of adenohypophyseal and neurohypophyseal hormones to CRH in eight patients (age 26–64 years, six female) with suspected pituitary‐dependent Cushing's syndrome during bilateral, simultaneous inferior petrosal sinus catheterization. Blood samples were taken from both petrosal sinuses and a peripheral vein before, and at 5‐min intervals for 15 min after, an intravenous injection of 100 μg human CRH1–41. CRH increased sinus AVP concentrations in all eight patients and OXT concentrations in four of five patients studied. Although AVP concentrations often increased in both sinuses, the side of maximal AVP rise was termed sidemax‐AVP. CRH did not affect peripheral or petrosal sinus mean concentrations of LH, FSH, GH or TSH. While there was no change in mean peripheral concentrations of AVP, OXT, ACTH, ACTH precursors or prolactin after CRH, sinus concentrations of OXT, ACTH and prolactin on sidemax‐AVP were markedly elevated over contralateral values. CRH did not increase mean sinus concentrations of ACTH precursors. In seven patients with either no radiological abnormality of the pituitary fossa or a small adenoma the mean ACTH precursor/ACTH ratio in blood sampled from all sites was 2.1 |Mp 0.16 (mean |Mp SEM, n = 50). In a patient with a large, locally invasive tumour the mean ACTH precursor/ACTH molar ratio was 32.1 |Mp 1.3 (n = 12; P > 0.001), suggesting that alterations in this molar ratio may reflect the biological properties of the tumour. The source of CRH‐stimulatable AVP and OXT remains uncertain. While it is recognized that the data were accumulated in patients with pathology of the hypothalamo—hypophyseal—adrenal axis, these observations suggest a novel relationship between AVP, OXT and CRH in the regulation of ACTH secretion in man. We suggest that the relation between plasma AVP and corticosteroids seen in clinical hypoadrenal states could be explained by chronic stimulation of AVP secretion by CRH.