Characterization of corticotropin-releasing hormone receptors on human pituitary corticotroph adenomas and their correlation with endogenous glucocorticoids.
Specific receptors for CRH were identified in five freshly excised pituitary adenomas causing Cushing's disease. Their kinetic properties and mean affinity constant [1.45 +/- 0.38 (+/- SE) nmol/L] were comparable to the characteristics of rat and monkey anterior pituitary CRH receptors. No correlation was found between the immediate preoperative plasma and urinary cortisol levels and the number of pituitary adenoma CRH receptors, which ranged from 6-96 fmol/mg protein, unlike in rats, in which corticosterone modulates the number of anterior pituitary CRH receptors. The lack of correlation between the concentration of CRH receptors and plasma cortisol levels may reflect the inability of glucocorticoids to down-regulate CRH receptors in these tumors. Thus, corticotroph adenomas are resistant not only to the feedback actions of glucocorticoids on proopiomelanocortin synthesis and secretion but also to their actions on CRH receptors.
Grino
M
M
Laboratoire de Neuroendocrinologie Expérimentale, INSERM U 297, Marseille, France.
Guillaume
V
V
Boudouresque
F
F
Margioris
A N
AN
Grisoli
F
F
Jaquet
P
P
Oliver
C
C
Conte-Devolx
B
B
D000236:Adenoma / Q000032:analysis*; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000328:Adult; D003346:Corticotropin-Releasing Hormone / Q000502:physiology; D003480:Cushing Syndrome / Q000209:etiology; D005260:Female; D005938:Glucocorticoids / Q000502:physiology*; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis; D008875:Middle Aged; D010903:Pituitary Gland, Anterior; D010911:Pituitary Neoplasms / Q000032:analysis*; D018019:Receptors, Corticotropin-Releasing Hormone; D017981:Receptors, Neurotransmitter / Q000032:analysis*
D005938:Glucocorticoids; D018019:Receptors, Corticotropin-Releasing Hormone; D017981:Receptors, Neurotransmitter; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone