Non‐functioning pituitary adenomas do not regress during bromocriptine therapy but possess membrane‐bound dopamine receptors which bind bromocriptine

JS Bevan, CW Burke - Clinical Endocrinology, 1986 - Wiley Online Library
JS Bevan, CW Burke
Clinical Endocrinology, 1986Wiley Online Library
Dopaminergic binding to membranes from 20 well‐characterized non‐functioning pituitary
tumours was investigated using the radioligand [3H] spiperone; nine had failed to regress
during pre‐operative bromocriptine therapy. Five macro‐prolactinomas and six normal
pituitaries were similarly investigated. High affinity dopaminergic binding sites were defined
in all tissues studied. Mean dissociation constants were similar for the three groups (0.92,
0.55 and 0.51 nmol/l, respectively) but mean site numbers were greater in the prolactinomas …
Summary
Dopaminergic binding to membranes from 20 well‐characterized non‐functioning pituitary tumours was investigated using the radioligand [3H]spiperone; nine had failed to regress during pre‐operative bromocriptine therapy. Five macro‐prolactinomas and six normal pituitaries were similarly investigated. High affinity dopaminergic binding sites were defined in all tissues studied. Mean dissociation constants were similar for the three groups (0.92, 0.55 and 0.51 nmol/l, respectively) but mean site numbers were greater in the prolactinomas (698) than in non‐functioning tumours (131) or normal pituitaries (136 fmol/mg protein). In a pool of non‐functioning tumour membranes ligand competition experiments confirmed that binding was dopaminergic. Stereospecificity was demonstrated using the (+) and (−) isomers of butaclamol. Bromocriptine was present in three non‐functioning tumours that had been exposed to the drug within 24 h of surgery and it largely prevented [3H]spiperone binding; membrane washing restored [3H]spiperone binding to control values. We conclude that non‐functioning tumours possess high affinity membrane‐bound dopaminergic binding sites similar to those in normal pituitary and macroprolactinomas, but apparently fewer in number than in the latter. Though bromocriptine binds to dopamine receptors on non‐functioning tumours in vivo, this does not result in tumour regression.
Wiley Online Library