TY - JOUR
T1 - Developmental and hormonal regulation of cholesterol side chain cleavage cytochrome P-450 in the fetal rabbit testis
AU - Anderson, Christen M.
AU - Mendelson, Carole R.
N1 - Funding Information:
This research was supported, in part, by NIH Grants Nos. AM31206 and AGO0306. * Supported by NIH Training Grant HD07190. Current address: Dept. of Internal Medicine, University of California at San Diego School of Medicine, San Diego, CA 92122, U.S.A.
PY - 1988/2
Y1 - 1988/2
N2 - Male sexual differentiation is dependent upon the induction of testosterone synthesis by the fetal testis at a critical phase of development. In the rabbit, testosterone synthesis by the fetal testis is initiated after 17.5-18 days of gestation, reaches peak values by day 21 and subsequently declines. In the present study, we analyzed the specific activity and concentration of immunoreactive cholesterol side chain cleavage cytochrome P-450 (cytochrome P-450scc) in the fetal rabbit testis during development to assess its possible role as a key regulatory enzyme in fetal testicular Steroidogenesis. The effects of human chorionic gonadotropin (hCG) and dibutyryl cyclic AMP on the specific activity and synthesis of cytochrome P-450scc in fetal rabbit testes in vitro also were evaluated. We observed that changes in cholesterol side chain cleavage activity paralleled the induction of testosterone synthesis; the specific activity of this enzyme which was {reversed tilde equals}- 0.25 pmol min-1 mg-1 protein in testes from 19-day fetal rabbits was increased {reversed tilde equals}- 10-fold in testes of 21-day fetuses and thereafter declined dramatically. Immunoreactive cytochrome P-450scc, which was first detectable in gonads of 19-day fetal rabbits, was induced markedly in 21-day fetal testes, reached maximum levels on day 24 and declined slightly thereafter. Incubation of testes from 19-and 21-day gestational age fetal rabbits with hCG or dibutyryl cyclic AMP for 24 h resulted in an induction of testosterone synthesis, cholesterol side chain cleavage activity and synthesis of cytochrome P-450scc. These findings are suggestive that androgen synthesis by the fetal Leydig cell is mediated by an induction of the synthesis and specific activity of cytochrome P-450scc. In addition, these data support the hypothesis that the developmental changes in the synthesis of cytochrome P-450scc are regulated by fetal gonadotropin and are mediated by cyclic AMP.
AB - Male sexual differentiation is dependent upon the induction of testosterone synthesis by the fetal testis at a critical phase of development. In the rabbit, testosterone synthesis by the fetal testis is initiated after 17.5-18 days of gestation, reaches peak values by day 21 and subsequently declines. In the present study, we analyzed the specific activity and concentration of immunoreactive cholesterol side chain cleavage cytochrome P-450 (cytochrome P-450scc) in the fetal rabbit testis during development to assess its possible role as a key regulatory enzyme in fetal testicular Steroidogenesis. The effects of human chorionic gonadotropin (hCG) and dibutyryl cyclic AMP on the specific activity and synthesis of cytochrome P-450scc in fetal rabbit testes in vitro also were evaluated. We observed that changes in cholesterol side chain cleavage activity paralleled the induction of testosterone synthesis; the specific activity of this enzyme which was {reversed tilde equals}- 0.25 pmol min-1 mg-1 protein in testes from 19-day fetal rabbits was increased {reversed tilde equals}- 10-fold in testes of 21-day fetuses and thereafter declined dramatically. Immunoreactive cytochrome P-450scc, which was first detectable in gonads of 19-day fetal rabbits, was induced markedly in 21-day fetal testes, reached maximum levels on day 24 and declined slightly thereafter. Incubation of testes from 19-and 21-day gestational age fetal rabbits with hCG or dibutyryl cyclic AMP for 24 h resulted in an induction of testosterone synthesis, cholesterol side chain cleavage activity and synthesis of cytochrome P-450scc. These findings are suggestive that androgen synthesis by the fetal Leydig cell is mediated by an induction of the synthesis and specific activity of cytochrome P-450scc. In addition, these data support the hypothesis that the developmental changes in the synthesis of cytochrome P-450scc are regulated by fetal gonadotropin and are mediated by cyclic AMP.
KW - (Testis
KW - Cholesterol side chain cleavage
KW - Fetal development
KW - Rabbit)
KW - Steroidogenesis
UR - http://www.scopus.com/inward/record.url?scp=0023872503&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0023872503&partnerID=8YFLogxK
U2 - 10.1016/0303-7207(88)90126-8
DO - 10.1016/0303-7207(88)90126-8
M3 - Article
C2 - 3356301
AN - SCOPUS:0023872503
SN - 0303-7207
VL - 55
SP - 121
EP - 130
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
IS - 2-3
ER -