Pharmacology of ovine and human CRH.
In primates, ovine and human CRH cause ACTH- and cortisol secretion in a dose-dependent fashion. Ovine CRH has a half-life, which is about three times longer than that of human CRH and results in long lasting ACTH- and cortisol responses. Plasma ACTH- and cortisol rises after administration of human CRH mimic the spontaneously occurring secretory episodes of these hormones in man. Pulsatile administration of human CRH restores the diurnal secretory pattern of ACTH and cortisol to normal in patients with apparent CRH deficiency. Facial and upper body flush occur in about 20% of patients receiving intravenously a 1 microgram/kg dose of CRH. Higher doses result in hypotension due to a decrease in peripheral vascular resistance. The latter is primarily due to dilatation of the superior mesenteric vessels. In in vitro models desensitization of the pituitary corticotroph by continuous, high-dose CRH administration occurs. No down-regulation of ACTH- and cortisol secretion has been shown in vivo, however. Pituitary-adrenal responsiveness to CRH can be modulated by many factors. These factors are involved in the basal regulation of the hypothalamic-pituitary-adrenal axis and in its activation during the stress response. Such factors include AVP, morphine, DAMME, and drugs modulating the endogenous serotoninergic and GABA/benzodiazepine system. Glucocorticoid feedback inhibition of the pituitary is one of the most important factors modulating ACTH- and cortisol responses to CRH. A negative correlation exists between the net ACTH- and cortisol response to exogenous CRH and the basal cortisol plasma concentration. Replacement doses of glucocorticoid result in a drastic decrease of basal plasma concentrations of cortisol and adrenal androgens.(ABSTRACT TRUNCATED AT 250 WORDS)
Schürmeyer
T H
TH
Abteilung Klinische Endokrinologie, Medizinische Hochschule Hannover, Germany.
Schulte
H M
HM
Avgerinos
P C
PC
Tomai
T P
TP
Loriaux
D L
DL
Gold
P W
PW
Chrousos
G P
GP
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D010902:Pituitary Gland / Q000187:drug effects / Q000502:physiology; D012756:Sheep
D005938:Glucocorticoids; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone