• Journal of Genetic Medicine
• /
• 제20권1호
• /
• pp.25-29
• /
• 2023

The CYP11A1 gene encodes for the cholesterol side-chain cleavage enzyme (P450scc), which initiates steroid hormone biosynthesis. Defective P450scc activity results in severe glucocorticoid and mineralocorticoid deficiencies. We describe a case of P450scc deficiency due to a novel homozygous CYP11A1 variant inherited from the mother with a possibility of uniparental disomy (UPD). The patient was a female, had no family history of endocrine disease, and showed adrenal insufficiency at 13 days of age. Hormonal analysis with an adrenocorticotropic hormone stimulation test showed both glucocorticoid and mineralocorticoid deficiencies, presumed to be a defect of the early stage of steroidogenesis. Exome sequencing reported a novel homozygous frameshift variant of CYP11A1 (c.284_285del, p.Asn95Serfs*10), which was inherited from the mother. Additionally, homozygosity in 15q22.31q26.2, which included CYP11A1, was identified using a chromosomal microarray. It was suggested that the possibility of maternal UPD was involved as the cause of a P450scc deficiency by unmasking the maternally derived affected allele. To our understanding, P450scc deficiency associated with UPD encompassing CYP11A1 had not been reported in Korea before. Genetic analysis can help diagnose rare causes of primary adrenal insufficiency, including P450scc deficiency.

• Asian-Australasian Journal of Animal Sciences
• /
• 제22권5호
• /
• pp.618-625
• /
• 2009

The objective of this work was to study the direct effects of daidzein on steroidogenesis in cultured mouse Leydig cells. Adult mouse Leydig cells were purified by Percoll gradient centrifugation, and the cell purity was determined using a $3{\beta}$-hydroxysteroid dehydrogenase ($3{\beta}$-HSD) staining method. The purified Leydig cells were exposed to different concentrations ($10^{-7}$ M to $10^{-4}$ M) of daidzein for 24 h under basal and human chorionic gonadotropin (hCG)-stimulated conditions. The cell viability and testosterone production were determined, and the related mechanisms of daidzein action were also evaluated using the estrogen receptor antagonist ICI 182,780 and measuring the mRNA levels of steroidogenic acute regulatory protein (StAR), cholesterol side-chain cleavage enzyme (P450scc), and $3{\beta}$-HSD-1 involved in testosterone biosynthesis. The results revealed that daidzein did not influence cell viability. Daidzein increased both basal and hCG-stimulated testosterone production in a dose-dependent manner, and this effect was statistically significant at concentrations of $10^{-5}$ M and $10^{-4}$ M daidzein (p<0.05). ICI 182,780 had no influence on daidzein action. RTPCR results revealed that $10^{-5}$ M and $10^{-4}$ M daidzein did not exert any obvious influence on the mRNA level of P450scc in Leydig cells. However, in the presence of hCG, these concentrations of daidzein significantly increased the StAR and $3{\beta}$-HSD-1 mRNA levels (p<0.05), but in the absence of hCG, only $10^{-5}$ M and $10^{-4}$ M daidzein up-regulated the StAR and $3{\beta}$-HSD-1 mRNA expression (p<0.05), respectively. These results suggest that daidzein has direct effect on Leydig cells. Daidzein-induced increase of testosterone production is probably not mediated by the estrogen receptor but correlates with the increased mRNA levels of StAR and $3{\beta}$-HSD-1.

• 한국가축번식학회지
• /
• 제24권4호
• /
• pp.395-406
• /
• 2000

본 연구는 다양한 농도의 FSH 와 LH 에서 배양된 생쥐 preantral follicles 내 난자의 발생능력을 조사하고, 이러한 조건에서 배양된 난자 -난구세포 복합체에서 황체화의 지표인 cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc)와 퇴행화의 지표인 cytochrome P450 17 $\alpha$ -hydroxylase (P450$_{17{\alpha}}$ ) mRNA의 발현정도를 조사하고, 또한 progesterone과 testosterone의 분비농도를 살펴보기 위하여 실시하였다. 체외성장된 난자의 배반포까지의 발달능력은 100 $m\ell$U/$m\ell$ FSH 단독첨가군 (30.2%)과 100 $m\ell$U/$m\ell$ FSH$\pm$l0$m\ell$U/$m\ell$ LH 첨가군 (28.0%)이 100$m\ell$U/$m\ell$ FSH＋100$m\ell$U/$m\ell$ LH 첨가군 (22.0%) 보다 높은 결과를 나타냈다. 그리고 배반포의 평균 세포수에 있어서도 FSH 단독첨가군 (50.9$\pm$26.1)과 100$m\ell$U/$m\ell$ FSH＋10 $m\ell$U/$m\ell$LH 첨가군 (51.0$\pm$26.1)이 100$m\ell$U/$m\ell$ FSH＋100$m\ell$U/$m\ell$ LH 첨가군 (45.2$\pm$15.1) 보다 많은 것으로 조사되었다. 난자 -난구세포 복합체에서 P450scc 와 P450$_{17{\alpha}}$의 발현은 LH의 첨가농도가 증가함에 따라서 증가하였으며, 그리고 progesterone과 testosterone의 분비도 증가를 하였다. 특히, P450scc 와 P450$_{17{\alpha}}$ 의 발현 그리고 progesterone과 testosterone의 분비는 100$m\ell$U/$m\ell$ FSH＋100$m\ell$U/$m\ell$ LH 첨가군에서 다른 첨가군들에 비하여 유의하게 증가하였다. 따라서, 이러한 결과들은 성선자극호르몬이 preantral follicles의 체외배양을 위해서는 필수적이지만, LH 첨가농도의 증가는 난자의 발생능력을 감소시킨다는 것을 보여주었다. 그리고 이러한 결과에 대한 원인의 하나는 황체화의 지표인 P450scc와 퇴행화의 지표인 P450$_{17{\alpha}}$ 발현의 증가에 의한 progesterone과 testosterone의 분비증가에 기인한 것으로 추정된다. 결론적으로, 본 연구는 배양액내에 100$m\ell$U/$m\ell$ FSH 혹은 100$m\ell$U/$m\ell$ FSH+10 $m\ell$U/$m\ell$ LH 의 첨가가 생쥐 preantral follicles의 체외배양을 위한 적정조건임을 제시하고 있다.

• 환경생물
• /
• 제22권4호
• /
• pp.550-558
• /
• 2004

The effects of postnatal exposure to octylphenol(OP) on the expressions of the steroidogenic enzymes and testosterone production were evaluated. Postnatal male mice (15-day-old) were injected with 2 or 20mg $kg^{-l}$ body weight (BW) of OP for 5 days and sacrificed on postnatal day 21. Testosterone concentration was measured by radioimmunoassay and the expressions of the testicular genes were determined by RT-PCR analyses. Significant reductions in the mean body and testis weight were observed in the OP treated animals. No marked alteration in the histological structure of the testis were observed, however, slight reduction in the seminiferous tubule diameter and the number of Leydig cells and several pyknotic cells could be identified in the 20 mg $kg^{-l}$ BW of the OP treated animals. Serum testosterone concentration was dramatically reduced and the mRNA expressions of the steroidogenic acute regulatory protein (StAR), cholesterol side-chain cleavage enzyme (P450scc) and $17\beta$-hydroxylase/Cl7-20 lyase $(P450_{17\alpha})$ were decreased. No significant changes of the gene expressions of the steroidogenic factor-l (SF-I) and estrogen and androgen receptor after the OP treatment showed that the decreased expressions of the steroidogenic enzymes in the present study did not correlate with these genes. Altogether, the present study demonstrates that postnatal treatment of OP inhibits steroidogenesis by decreasing the transcriptional expressions of the StAR and steroidogenic enzymes. The alteration in steroidogenesis may adversely affect the normal development of the testis and sper- matogenesis.