Effect of DL111-IT on progesterone biosynthesis and viability of rat luteal cells in vitro
Abstract
AIM: To study the influence of DL111-IT on progesterone biosynthesis of cultured
luteal cells (LC).
METHODS: LC viability was assessed with trypan blue dye exclusion and
progesterone concentration was measured with radioimmunoassay.
RESULTS: DL111-IT decreased the viability of LC after 24-h incubation, its ED50
being 7.7 (95% confidence limits: 7.1-8.5) mg.L-1. DL111-IT inhibited basal
secretion of progesterone in a concentration-dependent manner, and 3 mg.L-1
decreased progesterone concentration by 25% vs control. DL111-IT 3 mg.L-1 also
inhibited the stimulatory effect of forskolin (cAMP activator) 10 mumol.L-1 and
pregnenolone [converted to progesterone by 3 beta-hydroxysteroid
dehydrogenase-isomerase complex (3 beta-HSD)] 10 mumol.L-1 on progesterone
production in cultured LC, and their inhibitory rates were 43% and 155%,
respectively. At the same concentration, DL111-IT did not influence hCG-induced
progesterone production.
CONCLUSION: DL111-IT inhibited progesterone synthesis by suppressing the
conversion of pregnenolone to progesterone (inactivating 3 beta-HSD) and
suppressed the activity of cAMP. DL111-IT 6-24 mg.L-1 decreased the viability of
LC.
Keywords:
luteal cells (LC).
METHODS: LC viability was assessed with trypan blue dye exclusion and
progesterone concentration was measured with radioimmunoassay.
RESULTS: DL111-IT decreased the viability of LC after 24-h incubation, its ED50
being 7.7 (95% confidence limits: 7.1-8.5) mg.L-1. DL111-IT inhibited basal
secretion of progesterone in a concentration-dependent manner, and 3 mg.L-1
decreased progesterone concentration by 25% vs control. DL111-IT 3 mg.L-1 also
inhibited the stimulatory effect of forskolin (cAMP activator) 10 mumol.L-1 and
pregnenolone [converted to progesterone by 3 beta-hydroxysteroid
dehydrogenase-isomerase complex (3 beta-HSD)] 10 mumol.L-1 on progesterone
production in cultured LC, and their inhibitory rates were 43% and 155%,
respectively. At the same concentration, DL111-IT did not influence hCG-induced
progesterone production.
CONCLUSION: DL111-IT inhibited progesterone synthesis by suppressing the
conversion of pregnenolone to progesterone (inactivating 3 beta-HSD) and
suppressed the activity of cAMP. DL111-IT 6-24 mg.L-1 decreased the viability of
LC.