Abnormal dopamine sensitivity in some human prolactinomas.
In most of human prolactin (PRL)-secreting adenomas, dopamine and dopamine agonists normally suppress the excessive PRL secretion. Nevertheless, a subpopulation of such patients presents a relative insensitivity to the ergot derivative bromocriptine. Six patients with a macroadenoma (n = 5) or microadenoma (n = 1) were considered resistant to bromocriptine which, at a daily dose of 15-60 mg, did not normalize high plasma PRL levels. Culture studies of these adenoma cells showed that: (1) 10(-8) M bromocriptine produced a 32 +/- 16% inhibition of PRL release versus 65 +/- 12% obtained in the same conditions with normal human pituitary cells; (2) sulpiride (10(-6) M) reversed the inhibitory effects of bromocriptine, and (3) the bacterial endotoxins, cholera toxin (10(-11) M) and pertussis toxin (250 ng/ml), respectively, produced a 45-500% increase and a total abolition of bromocriptine-induced PRL inhibition. These observations and recent data of the literature allow to discuss the possibility of receptor or postreceptor defects in such tumors.
Pellegrini
I
I
Laboratoire de Neuroendocrinologie Expérimentale, Faculté de Médecine Nord, INSERM U 297, Marseille, France.
Costa
R
R
Grisoli
F
F
Jaquet
P
P
D001971:Bromocriptine / Q000494:pharmacology; D002478:Cells, Cultured; D004298:Dopamine / Q000494:pharmacology*; D005260:Female; D006801:Humans; D010911:Pituitary Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D015175:Prolactinoma / Q000503:physiopathology*; D011954:Receptors, Dopamine / Q000502:physiology*
D011954:Receptors, Dopamine; D001971:Bromocriptine; D004298:Dopamine