title: Effects of the 3β-hydroxysteroid dehydrogenase inhibitor trilostane on luteal progesterone production in the dog.
abstract: Interference with the pregnancy-maintaining influence of progesterone is the basis of most methods for termination of unwanted pregnancy in dogs. The currently available methods are based on induction of luteolysis or blocking of the progesterone receptor. Inhibition of progesterone synthesis using a competitive inhibitor of 3β-hydroxysteroid dehydrogenase (3β-HSD) could be another strategy to terminate unwanted pregnancies. In this study we investigated the effects of the 3β-HSD inhibitor trilostane on corpus luteum function in non-pregnant bitches. Trilostane was administered orally for seven consecutive days in either the pituitary-independent part of the luteal phase (PIP, start of treatment on D11 after ovulation, n = 6) or the pituitary-dependent part (PDP, start of treatment on D31 after ovulation, n = 6), in an oral dose of about 4.5 mg/kg bw, twice daily. Results were compared with those obtained in control bitches (n = 6). ACTH stimulation tests were performed to assess adrenocortical reserve capacity. Trilostane caused no apparent side effects and ACTH stimulation tests revealed good suppression of cortisol secretion. Trilostane also caused a significant decrease in plasma progesterone concentration. When it was stopped during PIP, progesterone secretion was completely restored and there was no difference in the length of the luteal phase between those dogs and control dogs (99 days, range 70-138 d and 99 d, range 60-112 d, respectively). When trilostane was stopped during PDP there was no post-treatment recovery of progesterone secretion and although the luteal phase tended to be shorter (66 d, range 41-101 d) the difference was not significant (P = 0.09). Plasma prolactin concentration did not increase after the trilostane-induced decrease in plasma progesterone. The interoestrous interval in dogs treated during PIP (234 d, range 175-269 d) or PDP (198 d, range 120-287 d) was not significantly shorter than the control interval (247 d, range 176-313 d). In conclusion, trilostane treatment was effective in decreasing plasma progesterone concentration in bitches during the luteal phase, but the dose regimen used in this study produced less clear-cut inhibition of ovarian steroidogenesis than have other strategies to decrease plasma progesterone concentration. Further studies are warranted to determine whether trilostane can be used to terminate unwanted pregnancy in the bitch without inducing adrenocortical insufficiency.
authors.affiliation: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands. J.deGier@uu.nl
authors.forename: J
authors.initials: J
authors.lastname: de Gier
authors.forename: C H J
authors.initials: CH
authors.lastname: Wolthers
authors.forename: S
authors.initials: S
authors.lastname: Galac
authors.forename: A C
authors.initials: AC
authors.lastname: Okkens
authors.forename: H S
authors.initials: HS
authors.lastname: Kooistra
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors; D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D000818:Animals; D013196:Dihydrotestosterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D008183:Luteal Phase / Q000097:blood / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010060:Ovulation / Q000097:blood / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D011247:Pregnancy; D011374:Progesterone / Q000097:blood / Q000378:metabolism*; D011388:Prolactin / Q000097:blood / Q000378:metabolism; D013997:Time Factors
chemical_list: D004791:Enzyme Inhibitors; D013196:Dihydrotestosterone; D011374:Progesterone; D011388:Prolactin; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase; C009954:trilostane