Regulation of Pulsatile and Entropic ACTH Secretion under Fixed Exogenous Secretagogue Clamps.

Regulation of Pulsatile and Entropic ACTH Secretion under Fixed Exogenous Secretagogue Clamps.

J Clin Endocrinol Metab. 2017 Mar 28;:

Authors: Roelfsema F, Aoun P, Takahashi PY, Erickson D, Yang R, Veldhuis JD

Abstract
Background: Studies of ACTH secretion are hampered by unobservable hypothalamic CRH and AVP pulses. Clamping one of the secretagogues could allow indirect quantification of the impact of the endogenous heterotypic hormone.
Methods: Randomized, double-blind, placebo-controlled cross-over study in 28 healthy adults (16 men), mean age 55 yr. Volunteers received leuprolide, followed by placebo or sex-steroid addback. Eucortisolemia was accomplished by oral ketoconazole and continuous iv cortisol administration with 10 h of 10-min sampling. To clamp secretagogue inputs overnight double-blind continuous iv infusions of CRH, AVP, both peptides, or saline were employed, followed by a single bolus dose of the non-infused peptide with blood sampling for 2.5 h.
Results: Mean ± SEM 10-h ACTH concentrations (ng/L) in the gender-combined analysis were: saline 32±4.6, AVP 29±4.6, CRH 67±6.2 and CRH-AVP 67±8.8: CRH vs AVP, P<0.0001. Mean 10-h cortisol was higher in women than men (P<0.0001), and higher during CRH than AVP infusion (P<0.0001). ApEn was increased by AVP and CRH (P<0.0001). AVP injection yielded a 2.5-h ACTH concentration of 46±4.3, exceeding that after CRH or saline injection (26±3.3 and 24±3.6, respectively; P=0.002 and 0.001). Sex-hormone administration was not a significant categorical variable.
Conclusions: ACTH-secretagogue clamps yield continued pulsatile ACTH secretion, but with higher ACTH secretory-burst mass and randomness especially in the presence of CRH. AVP infusions failed to sustain increased ACTH secretion, approaching saline infusion. Conversely, after sustained CRH infusion, AVP, but not CRH injection induced marked ACTH release, likely caused by heterotypic sensitization of corticotropes by CRH.

PMID: 28368521 [PubMed - as supplied by publisher]

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