Neuroendocrinological effects of ketoconazole in rats.
The effect of ketoconazole on steroid synthesis was studied in intact (sham-operated) and castrated male and ovariectomized female rats. Rats were given 25 mg/kg ketoconazole twice a day im for 5 days. The influence of ketoconazole was also investigated on hormone release altered by GnRH, estradiol and haloperidol. The following hormones were measured: serum LH, PRL, testosterone, corticosterone, 17-OH-progesterone, estradiol, and dopamine content of the tubero-infundibular area. Ketoconazole treatment resulted in a significant decrease of testerone level (from 7.93 +/- 1.99 to 3.83 +/- 0.94 nmol/l), whereas LH, PRL, corticosterone and 17-OH-progesterone remained unchanged in the male rat. The effect of castration on LH level was reduced by ketoconazole in male (from 590 +/- 35 to 390 +/- 25 micrograms/l) and female rats (from 468 +/- 22 to 346 +/- 39 micrograms/l), but the GnRH-stimulated LH release in castrated and ovariectomized animals was unchanged. The suppressive action of estradiol on LH in ovariectomized rats was enhanced (from 160 +/- 41 to 64.6 +/- 12.9 micrograms/l), and its priming effect on PRL release was diminished by ketoconazole (from 598 +/- 81 to 281 +/- 66 micrograms/l). Ketoconazole failed to modify the tubero-infundibular dopamine content and haloperidol-induced PRL release. It can be assumed that in addition to its inhibitory role of steroid biosynthesis ketoconazole has an influence on central mechanisms underlying LH and PRL release.
Irsy
G
G
1st Department of Medicine, Postgraduate Medical School, Budapest, Hungary.
Koranyi
L
L
D000818:Animals; D004298:Dopamine / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology*; D007654:Ketoconazole / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D009919:Orchiectomy; D010052:Ovariectomy; D010902:Pituitary Gland / Q000187:drug effects / Q000502:physiology*; D011388:Prolactin / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013739:Testosterone / Q000097:blood
D013739:Testosterone; D004958:Estradiol; D011388:Prolactin; D007986:Luteinizing Hormone; D006220:Haloperidol; D007654:Ketoconazole; D004298:Dopamine