Differential effects of ketoconazole on prolactin and growth hormone release by normal and tumoral rat anterior pituitary cells in vitro.
The imidazole derivative ketoconazole (1-100 microM) was shown to stimulate the release of prolactin (PRL) from rat anterior pituitary cells in vitro. In contrast, this drug did not affect growth hormone (GH) release from the same cells. In addition, ketoconazole was found to have no effect on PRL or GH release from a tumoral pituitary cell clone (GH3). Treatment of normal pituitary cells with ketoconazole (10 microM) for more than 20 min abolished TRH-induced hormone release. TRH-stimulated release was both attenuated and delayed in the ketoconazole-treated tumoral cells. Ketoconazole (10 microM) did not affect the basal electrophysiological properties of GH3 cell membranes, although it did affect the TRH-induced response. The action of ketoconazole of the spontaneous release of PRL by normal cells and the TRH-stimulated release of PRL and GH is consistent with an interference with arachidonic acid metabolism.
Drouhault
R
R
Laboratoire de Neurophysiologie, UA CNRS 1200, Université de Bordeaux II, France.
Vacher
P
P
David
J P
JP
Courtes
A M
AM
Vilayleck
N
N
Dufy
B
B
D000818:Animals; D004594:Electrophysiology; D005260:Female; D013006:Growth Hormone / Q000378:metabolism*; D066298:In Vitro Techniques; D007654:Ketoconazole / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D010903:Pituitary Gland, Anterior / Q000187:drug effects* / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D013973:Thyrotropin-Releasing Hormone / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D013973:Thyrotropin-Releasing Hormone; D011388:Prolactin; D013006:Growth Hormone; D007654:Ketoconazole