Regulation of cytochrome P450 cholesterol side-chain cleavage, 3β-hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase type 1 and estradiol-17β-hydroxysteroid dehydrogenase mRNA levels by calcium in human choriocarcinoma JEG-3 cells

Beaudoin, Claude; Bonenfant, Martin; Tremblay, Yves

doi:10.1016/s0303-7207(97)00143-3

Cited by 24 publications

(12 citation statements)

References 48 publications

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“…HSD3B1 and HSD3B2 share their coding sequences and promoters, suggestive of the presence of some common regulatory mechanism (Simard et al, 2005). Calcium signaling was reported to be partly involved in the regulation of both HSD3B1 and HSD3B2 expression (Beaudoin et al, 1997; Nogueira et al, 2009). Further possible analyses of whether and to what extent HSD3B1 and HSD3B2 are differently regulated through intracellular calcium signaling are therefore considered important to understand the different degrees of associations detected between HSD3B isoforms and KCNJ5 mutation.…”

Section: Discussionmentioning

confidence: 99%

3β-hydroxysteroid dehydrogenase isoforms in human aldosterone-producing adenoma

Konosu-Fukaya

Nakamura

Satoh

et al. 2015

Molecular and Cellular Endocrinology

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It has become important to evaluate the possible involvement of 3β-hydroxysteroid dehydrogenase type 1 (HSD3B1) and 2 (HSD3B2) isoforms in aldosterone-producing adenoma (APA). In this study, we studied 67 and 100 APA cases using real-time quantitative PCR (qPCR) and immunohistochemistry, respectively. Results of qPCR analysis demonstrated that HSD3B2 mRNA was significantly more abundant than HSD3B1 mRNA (P < 0.0001), but only HSD3B1 mRNA significantly correlated with CYP11B2 (aldosterone synthase) mRNA (P < 0.0001) and plasma aldosterone concentration (PAC) of the patients (P < 0.0001). Results of immunohistochemistry subsequently revealed that HSD3B2 immunoreactivity was detected in the great majority of APA but a significant correlation was also detected between HSD3B1 and CYP11B2 (P < 0.0001). In KCNJ5 mutated APA, CYP11B2 mRNA (P < 0.0001) and HSD3B1 mRNA (P = 0.011) were significantly higher than those of wild type APA. These results suggest that HSD3B1 is involved in aldosterone production, despite its lower levels of expression compared with HSD3B2, and also possibly associated with KCNJ5 mutation in APA.

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Section: Discussionmentioning

confidence: 99%

3β-hydroxysteroid dehydrogenase isoforms in human aldosterone-producing adenoma

Konosu-Fukaya

Nakamura

Satoh

et al. 2015

Molecular and Cellular Endocrinology

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“…It is more likely that the observed effects are due to the interaction with receptor or cell signalling rather than cytotoxic responses. Moreover, gene transcription of 3␤-HSD1 has been reported to be affected by cellular adenosine 3 ,5 -cyclic monophosphate (cAMP) via a protein kinase (PK) A-dependent mechanism [20] and by cellular calcium content via a PKC-dependent pathway [29]. Perturbation of calcium homeostasis [30] and induction of cAMP level [31] by OTA may contribute to the modulation of 3␤-HSD1 mRNA expression.…”

Section: Discussionmentioning

confidence: 99%

Potential endocrine disrupting effect of ochratoxin A on human placental 3β-hydroxysteroid dehydrogenase/isomerase in JEG-3 cells at levels relevant to human exposure

Woo

Wan

Ahokas

et al. 2013

Reproductive Toxicology

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“…Cholesterol, the substrate for steroid hormone synthesis, must be transported to the inner mitochondrial membrane of the placenta where the cytochrome P450scc that catalyzes the cholesterol side chain cleavage reaction is located. The P450scc converts cholesterol from the inner mitochondrial membrane to pregnenolone, which is then rapidly converted to progesterone by type 1 3␤-hydroxysteroid dehydrogenase (2)(3)(4). In most steroidogenic tissues such as the corpus luteum, adrenal cortex, and testis, cholesterol translocation to the inner mitochondrial membrane is mediated by the steroidogenic acute regulatory protein (StAR), and this step is acutely regulated by tropic hormones (5,6).…”

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confidence: 99%

Molten Globule Structure and Steroidogenic Activity of N-218 MLN64 in Human Placental Mitochondria

et al. 2004

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Progesterone synthesis by the human placenta requires the conversion of mitochondrial cholesterol to pregnenolone by cytochrome P450scc. Most steroidogenic tissues use the steroidogenic acute regulatory protein (StAR) to deliver cholesterol to the inner mitochondrial membrane where P450scc is located, but StAR is not expressed in the human placenta. However, the human placenta does express MLN64, which has a C-terminal domain homologous to StAR that can also transport cholesterol. We investigated the ability of bacterially expressed N-218 MLN64 and N-62 StAR to transport cholesterol between artificial membranes and to its inner membrane site of use in placental mitochondria. Urea denaturation experiments show that N-218 MLN64 undergoes a pH-dependent and denaturant-dependent structural transition to a molten globule state, as reported previously for N-62 StAR. N-218 MLN64 stimulated cholesterol transfer between artificial phospholipid vesicles with an initial rate of 6.5 mol/min.mol N-218 MLN64. Both N-218 MLN64 and N-62 StAR stimulated cholesterol transfer to the inner mitochondrial membrane, as evidenced by a 6-fold stimulation of pregnenolone synthesis with saturating transporter. This stimulation was seen only after the endogenous cholesterol in the steroidogenic pool of the isolated mitochondria was first depleted. No stimulation was observed by N-218 MLN64 or N-62 StAR when 20alpha-hydroxycholesterol was added as substrate for P450scc, confirming that these proteins stimulate P450scc activity by enhancing cholesterol transport. MLN64 levels in placental JEG-3 cells were unresponsive to stimulation by 8-bromo-cAMP over 24 h. These data show that human N-218 MLN64 and N-62 StAR have similar biophysical and functional properties and are able to stimulate steroidogenesis in a human placental system, which normally lacks StAR. The results reveal that with saturating MLN64, steroidogenesis by placental mitochondria proceeds at near-maximal rate.

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Regulation of cytochrome P450 cholesterol side-chain cleavage, 3β-hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase type 1 and estradiol-17β-hydroxysteroid dehydrogenase mRNA levels by calcium in human choriocarcinoma JEG-3 cells

Cited by 24 publications

References 48 publications

3β-hydroxysteroid dehydrogenase isoforms in human aldosterone-producing adenoma

3β-hydroxysteroid dehydrogenase isoforms in human aldosterone-producing adenoma

Potential endocrine disrupting effect of ochratoxin A on human placental 3β-hydroxysteroid dehydrogenase/isomerase in JEG-3 cells at levels relevant to human exposure

Molten Globule Structure and Steroidogenic Activity of N-218 MLN64 in Human Placental Mitochondria

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