TY - JOUR
T1 - Effects of the 3β-hydroxysteroid dehydrogenase inhibitor trilostane on luteal progesterone production in the dog
AU - de Gier, J.
AU - Wolthers, C.H.
AU - Galac, S.
AU - Schaefers-Okkens, A.C.
AU - Kooistra, H.S.
PY - 2011
Y1 - 2011
N2 - 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 3 -hydroxysteroid dehydrogenase (3 -HSD) could
be another strategy to terminate unwanted pregnancies.
In this study we investigated the effects of the 3 -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.
© 2011 Elsevier Inc. All rights reserved.
AB - 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 3 -hydroxysteroid dehydrogenase (3 -HSD) could
be another strategy to terminate unwanted pregnancies.
In this study we investigated the effects of the 3 -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.
© 2011 Elsevier Inc. All rights reserved.
KW - Luteal phase
KW - Progesterone
KW - Prolactin
KW - ACTH stimulation test
KW - Cortisol
KW - Dog
U2 - 10.1016/j.theriogenology.2010.11.041
DO - 10.1016/j.theriogenology.2010.11.041
M3 - Article
SN - 0093-691X
VL - 75
SP - 1271
EP - 1279
JO - Theriogenology
JF - Theriogenology
IS - 7
ER -