Corticotropin-Releasing Factor (Ovine) and Vasopressin Exert a Synergistic Effect on Adrenocorticotropin Release in Man

Abstract

The effects of ovine CRF, lysine vasopressin (LVP), and their interrelationships, and rat hypothalamic extract (HME), on ACTH and beta-endorphin release by human pituitary tumor cells from two patients with Nelson's syndrome and one with Cushing's disease and on ACTH and cortisol secretion in vivo were studied. In cultured pituitary tumor cells, both LVP and CRF greatly stimulated ACTH and beta-endorphin release at maximally active concentrations of 0.1 microM and 10 nM, respectively. At these concentrations, the combination of the two substances had an additive or synergistic effect on hormone release. Low concentrations of HME potentiated and/or were synergistic with CRF-mediated ACTH release. In vivo, the combination of CRF (1 microgram/kg) and LVP (10 pressor units) induced greater ACTH release than the sum of the responses to CRF and LVP alone. This synergistic effect of CRF plus LVP concerned only ACTH release, while cortisol release after CRF plus LVP was equivalent to the sum of the maximal increments in this hormone after CRF and LVP alone. The peak levels of cortisol after a combination of CRF and LVP probably reflect the maximum stimulatory capacity of the adrenal cortex. These data support the concept that in man, both ovine CRF and vasopressin are corticotropin-releasing factors which act synergistically. Both substances might well regulate, at the pituitary level, the responsiveness of the pituitary-adrenal axis to stimuli reaching the hypothalamus. A test using ovine CRF and LVP together might provide a better index of total pituitary ACTH reserve than one using the two compounds separately.

A Synergistic Adrenocorticotropin Response to Naloxone and Vasopressin in Normal Humans: Evidence That Naloxone Stimulates Endogenous Corticotropin-Releasing Hormone

“…Intramuscular AVP or LVP in doses of 3-10 units has resulted in significant elevations of ACTH and cortisol lev els when given alone, as well as synergistic ACTH re sponses when administered with synthetic CRH [2][3][4]41]. However, no published studies of CRH/AVP synergy em ploying exogenous AVP have measured plasma AVP con centrations.…”

Localization and Quantification of Pro-Opiomelanocortin mRNA and Glucocorticoid Receptor mRNA in Pituitaries of Suicide Victims

“…A few small areas of POMC-positive cells did not seem to have CRH receptors in adjacent slides. Although this could be due to intrinsic variabilities in the two different methods used (i.e., autoradiography vs. in situ hybridization), or to the fact that the adjacent slides are 10 pm apart, it is also possible that some of the POMC cells lack CRH receptors and express receptors for other hypothalamic secretagogues, such as arginine vasopressin, a known stimulator of ACTH secretion [32,33], GR expression is widespread in the anterior pituitary, but their mRNA seems to be most highly concentrated in POMC cells. It is known from animal studies that other pituitary cells, such as lactotropes and somatotropes, are regulated by glucocorticoids, and that prolactin and growth hormone genes contain sequences that can bind the GR [34][35][36].…”

ACTH and cortisol response to combined corticotropin releasing hormone-arginine vasopressin stimulation in obese males and its relationship to body weight, fat distribution and parameters of the metabolic syndrome

“…This study was therefore carried out in obese men and appropriate normalweight controls to investigate the ACTH and cortisol response to the administration of a combined CRHa AVP stimulus, which provides a reliable physiological test for investigating pituitary ± adrenal functioning. 14 An additional aim of this study was to investigate the relationship between the activity of the HPA axis and several prominent parameters of the metabolic syndrome.…”