Effect of Passive Immunization against Corticotropin-Releasing Factor (CRF) on the Postadrenalectomy Changes of CRF Binding Sites in the Rat Anterior Pituitary Gland

Abstract

The concentration of corticotropin-releasing factor (CRF)-binding sites decreases in the rat anterior pituitary after adrenalectomy; this change may be related either to a direct effect of the circulating glucocorticoids at the pituitary level or to a desensitization of CRF receptors through an increased CRF release in hypophysial portal blood. In order to examine the latter possibility we have measured plasma adrenocorticotropin hormone (ACTH) levels and the number of anterior pituitary CRF binding sites in sham-operated and 24-hour adrenalectomized rats after blockade of endogenous CRF by passive immunization with an antiserum anti-rat CRF (CRF-AS), or after injection of normal rabbit serum (NRS). In NRS-injected rats, after sham operation, plasma ACTH concentration increased (227 + 34 vs. 118 ± 19 pg/ml in controls) without change in CRF-binding sites capacity (20.7 ± 2.6 vs. 24.6 ± 3.5 fmol/mg protein in controls). Adrenalectomy induced a large rise in plasma ACTH (785 ± 89 pg/ml) and a decrease in the number of CRF-binding sites (12.2 ± 1.7 fmol/mg protein). After CRF-AS injection, plasma ACTH was normalized in sham-operated animals (149 ± 24 pg/ml) and significantly reduced in adrenalectomized rats (472 ± 76 pg/ml); the adrenalectomy-induced decrease in the number of CRF-binding sites was unaffected by the CRF-AS administration (12.2 ± 1.7 fmol/mg protein). The administration of dexamethasone to adrenalectomized rats significantly reduced plasma ACTH concentrations (23.3 ± 10.6 pg/ml) and prevented the loss in CRF-binding sites capacity (20.7 + 1.3 fmol/mg protein). Affinity of CRF for its binding sites was unchanged in all the groups studied. These findings suggest that the postadrenalectomy reduction in the number of anterior pituitary CRF-binding sites may be mainly due to a direct glucocorticoid effect at the pituitary level rather than a consequence of a possible increased CRF secretion.

Changes in the Hypothalamo-Corticotrope Axis after Bilateral Adrenalectomy: Evidence for a Median Eminence Site of Glucocorticoid Action

“…Although the absolute amount CRF re leased under basal conditions by ME terminals was not affected after ADX ( fig. 3), it has been previously reported [24] that there is a fall in the CRF receptor density at the AP level after ADX. Then, it is possible to assume that the concentration of CRF in the portal blood after ADX could be high enough to activate a small number of functional AP CRF receptors; thus maintaining increased ACTH secretion [25].…”

Regional Serotonin Metabolism under Basal and Restraint Stress Conditions in the Brain of Transgenic Mice with Impaired Glucocorticoid Receptor Function

“…Plasma corticosterone levels were measured using a previously described radioimmunoassay method [22]. The lower detection limit was 2.5 ng/ml.…”

Homeostatic Regulation of Sleep in a Genetic Model of Depression in the Mouse: Effects of Muscarinic and 5-HT1A Receptor Activation

“…Serum was then collected and stored at À201C until further analysis. Corticosterone was quantified by radioimmunoassay after extraction in ethanol (Grino et al, 1987). Anticorticosterone antiserum was generously given by F Héry (INSERM U297, Marseille, France).…”

“…Anticorticosterone antiserum was generously given by F Héry (INSERM U297, Marseille, France). Corticosterone (Sigma) was used as standard and [ 3 H]corticosterone (87 Ci/mmol, Amersham-Pharmacia Biotech., Les Ulis, France) as radiotracer (Grino et al, 1987).…”