Corticotropin-Releasing Factor in the Dog Adrenal Medulla Is Secreted in Response to Hemorrhage*

Abstract

To characterize the nature of CRF-like immunoreactivity (CRF-LI) in the dog adrenal, adrenal medullary, adrenal cortical, or hypothalamic tissue was extracted and subjected to RIA after partial purification on C-18 cartridges or Sephadex G-50. Using N- and C-terminal-directed antisera against rat/human (r/h) CRF, significant levels of CRF-LI were found in the adrenal medulla and hypothalamus, but not in the adrenal cortex. Immunocytochemical analysis revealed that CRF-immunoreactive cells were located in the adrenal medulla, many of them concentrated in the vicinity of blood vessels and at the border between adrenal medulla and cortex. However, the cortex was devoid of any CRF-positive cells. On reverse phase HPLC, CRF-LI in the adrenal medulla coeluted with synthetic r/hCRF. In a bioassay system, using dispersed rat anterior pituitary cells, purified adrenal CRF caused a dose-dependent increase in ACTH secretion parallel to the r/hCRF standard, indicating that dog adrenal medulla contains authentic r/hCRF. Evidence of CRF-LI secretion from the adrenal was supported by its presence in adrenal venous, but not in peripheral arterial, plasma. Adrenal venous plasma CRF-LI coeluted with r/hCRF on reverse phase HPLC after affinity chromatographic purification. The CRF-LI secretory rate in conscious trained dogs was 68 +/- 19 pg/min (concentration, 27 +/- 5 pg/ml). In response to 20% hemorrhage, the CRF-LI secretion rate rose 3-fold within 15 min and was associated with increased catecholamine secretion. The existence of a biologically active CRF-like substance in the dog adrenal medulla and its secretion in conjunction with catecholamines after a hemorrhage suggest a physiological role for this peptide other than pituitary or central nervous system regulation.

Lack of Correlation Between Immunoreactive Corticotropin‐Releasing Factor Concentration Profiles in Hypophysial‐Portal and Peripheral Plasma

“…This strongly suggested an alternative, non-hypothalamic origin of irCRF-41 present in the systemic circulation. Multiple sources of peripheral irCRF-41 may be Postulated on the basis of immunohistochemical or content studies (18)(19)(20)(21)(22)(23)(24). Of particular interest were the adrenal glands, which contain and secrete CRF-like immunoreactivity (23,24).…”

“…Multiple sources of peripheral irCRF-41 may be Postulated on the basis of immunohistochemical or content studies (18)(19)(20)(21)(22)(23)(24). Of particular interest were the adrenal glands, which contain and secrete CRF-like immunoreactivity (23,24). Indeed, Bruhn et al (24) observed adrenal venous irCRF-41 concentrations of approximately 5 pmole/l in conscious, resting dogs which were increased 3-fold by 20% hemorrhage.…”

“…Of particular interest were the adrenal glands, which contain and secrete CRF-like immunoreactivity (23,24). Indeed, Bruhn et al (24) observed adrenal venous irCRF-41 concentrations of approximately 5 pmole/l in conscious, resting dogs which were increased 3-fold by 20% hemorrhage. While rat adrenal venous irCRF-41 levels (Table 3) were considerably higher than those found in dogs, adrenal irCRF-41 was similarly responsive to a hypotensive stimulus (Fig.…”

“…During pregnancy, peripheral irCRF-41 appears to be derived from the placenta (18)(19)(20). The source of peripheral irCRF-41 in non-pregnant animals is unknown and it has been postulated that it may reflect, at least in part, hypothalamic irCRF-41 secretion (13,14,16,17); other sources include the gastrointestinal tract (21), the pancreas (22) and the adrenal gland (23,24). In the present study, the relationship between peripheral and hypophysial-portal plasma concentration profiles of irCRF-41 was evaluated by direct measurements in both circulatory compartments under a variety of experimental conditions.…”

Action of Three Ectopeptidases on Corticotropin-Releasing Factor: Metabolism and Functional Aspects

“…In the periphery, the function of CRF remains obscure. Changes in plasma CRF concentrations have been observed during acute hemorrhage (Bruhn et al, 1987), insulin-induced hypoglycemia (Ellis et al, 1990), during pregnancy (Sasaki et al, 1984), and in depression (Catalan et al, 1998). CRF immunoreactivity has been observed in several peripheral tissues: adrenal medulla , testis (Yoon et al, 1988), the endocrine pancreas (Petrusz et al, 1984), and in lymphocytes Stephanou et al, 1990).…”