TY - JOUR
T1 - Inhibition of CYP450scc expression in dioxin-exposed rat Leydig cells
AU - Lai, K. P.
AU - Wong, M H
AU - Wong, C K C
N1 - Funding Information:
This work was supported by Group Research-Central Allocation of the Research Grants Council, University Grants Committee of Hong Kong and the Faculty Research Grant (FRG 02–03/I-01), Hong Kong Baptist University (to C K C W). The authors declare that there is no conflict of interest that would prejudice the impartiality of this scientific work.
Publisher copyright:
© 2005 Society for Endocrinology
PY - 2005/6
Y1 - 2005/6
N2 - Polychlorinated dibenzo-p-dioxins, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin
(TCDD) have been recognized as highly potent developmental and
reproductive toxins. We have previously demonstrated effects of TCDD in
modulating the expression of rat Sertoli cell secretory products and
markers for cell–cell interaction. In this study, we examined the direct
biological effects of TCDD in rat Leydig cell primary cultures. Mature
rat Leydig cells were purified by Percoll gradient centrifugation and
the cell purity was determined by 3β-hydroxysteroid dehydrogenase
(3β-HSD) staining and a testosterone induction assay. To examine
TCDD-induced biological consequences, we measured the changes in the
secretion of progesterone and testosterone, as well as transcript levels
of some selected steroidogenic enzymes (i.e. StAR, P450scc, 3β-HSD and
CYP17α), in TCDD/human chorionic gonadotropin (hCG) co-treated cells.
Our results indicated that TCDD (0.2 or 2 ng/ml) treatment significantly
suppressed hCG (5 or 10 ng/ml)-induced testosterone secretion. The
suppressive effect aligned with a reduction of progesterone secretion (P<0.05), as well as a decrease of P450scc mRNA and protein expression (P<0.05).
The mechanistic action of TCDD was found to be via the reduction of
cellular cAMP levels in the hCG-treated cells. This observation was
further confirmed, as the TCDD-mediated suppressive effect could be
reversed by dibutyryl cAMP co-treatment. The data indicate that TCDD can
modulate cAMP signaling in rat Leydig cells to affect the process of
steroidogenesis.
AB - Polychlorinated dibenzo-p-dioxins, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin
(TCDD) have been recognized as highly potent developmental and
reproductive toxins. We have previously demonstrated effects of TCDD in
modulating the expression of rat Sertoli cell secretory products and
markers for cell–cell interaction. In this study, we examined the direct
biological effects of TCDD in rat Leydig cell primary cultures. Mature
rat Leydig cells were purified by Percoll gradient centrifugation and
the cell purity was determined by 3β-hydroxysteroid dehydrogenase
(3β-HSD) staining and a testosterone induction assay. To examine
TCDD-induced biological consequences, we measured the changes in the
secretion of progesterone and testosterone, as well as transcript levels
of some selected steroidogenic enzymes (i.e. StAR, P450scc, 3β-HSD and
CYP17α), in TCDD/human chorionic gonadotropin (hCG) co-treated cells.
Our results indicated that TCDD (0.2 or 2 ng/ml) treatment significantly
suppressed hCG (5 or 10 ng/ml)-induced testosterone secretion. The
suppressive effect aligned with a reduction of progesterone secretion (P<0.05), as well as a decrease of P450scc mRNA and protein expression (P<0.05).
The mechanistic action of TCDD was found to be via the reduction of
cellular cAMP levels in the hCG-treated cells. This observation was
further confirmed, as the TCDD-mediated suppressive effect could be
reversed by dibutyryl cAMP co-treatment. The data indicate that TCDD can
modulate cAMP signaling in rat Leydig cells to affect the process of
steroidogenesis.
UR - http://www.scopus.com/inward/record.url?scp=21244443036&partnerID=8YFLogxK
U2 - 10.1677/joe.1.06054
DO - 10.1677/joe.1.06054
M3 - Journal article
C2 - 15930178
AN - SCOPUS:21244443036
SN - 0022-0795
VL - 185
SP - 519
EP - 527
JO - Journal of Endocrinology
JF - Journal of Endocrinology
IS - 3
ER -
