Structure and tissue-specific expression of 3ß-hydroxysteroid dehydrogenase/5-ene-4-ene isomerase genes in human and rat classical and peripheral steroidogenic tissues

Labrie, Fernand; Simard, Jacques; Luu‐The, Van; Pelletier, Georges; Bélanger, Alain; Lachance, Yves; Zhao, Huifen; Labrie, Claude; Breton, Nathalie; Launoit, Yvan de; Dumont, Martine; Dupont, Éric; Rhéaume, Éric; Martel, Céline; Couët, Jacques; Trudel, Claude

doi:10.1016/0960-0760(92)90368-s

Cited by 85 publications

(51 citation statements)

References 45 publications

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“…Pregnenolone, 17 α -hydroxypregnenolone and DHEA are all substrates for the 3 β -hydroxysteroid dehydrogenase/ ∆ 5/4 -isomerases (3 β HSDs), which irreversibly transform these ∆ 5 -steroids into their ∆ 4 -congenors. In human beings there are two 3 β HSDs: type 1 3 β HSD is found in liver, skin, placenta and other peripheral tissues, and type 2 3 β HSD (3 β HSD2) is expressed in adrenal and gonads (Lorence et al ., 1990;Rheaume et al ., 1991;Labrie et al ., 1992). Mutations in 3 βHSD2 cause a rare form of congenital adrenal hyperplasia (Rheaume et al, 1994;Simard et al, 2002), and these patients have elevated circulating concentrations of ∆ 5 -steroids, particularly 17α-hydroxypregnenlone (Lutfallah et al, 2002).…”

Section: β Hsds (β -Hydroxysteroid Dehydrogenase/ ∆ 5/4 -Isomerases)mentioning

confidence: 99%

Adrenarche – physiology, biochemistry and human disease

Auchus¹,

Rainey

2003

Clinical Endocrinology

258

148

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SummaryAdrenarche refers to the onset of dehydroepiandrosterone (DHEA) and DHEA-sulphate (DHEA-S) production from the adrenal zona reticularis that can be detected at around 6 years of age. The phenotypic result of adrenarche is pubarche or the development of axillary and pubic hair that occurs in both girls and boys at about age 8. The phenomenon of adrenarche is unique to human beings and to some Old World primates, and a reversal of adrenarche appears to occur in the ageing process. Premature and exaggerated adrenarche can be indicative of future onset of adult diseases, thus increasing the clinical relevance of adrenarche. The physiological triggers of adrenarche and the role(s) of DHEA-S remain speculative. However, the biochemical pathways that define adrenarche have been characterized in detail, and the appearance of key enzymes and cofactors in the adrenal zona reticularis track with the progression of adrenarche. This article reviews the clinical manifestations of adrenarche, the biochemistry of the enzymes involved in DHEA-S production, and the cell biology of the adrenal zona reticularis.Glucocorticoids and mineralocorticoids secreted by the adrenal glands are essential for the maintenance of vascular tone and carbohydrate metabolism or of blood volume and sodium balance, respectively. The testes and ovaries, by contrast, generate the sex steroids that are required for gametogenesis, secondary sexual characteristics and reproduction. However, the adrenal glands of adult human beings secrete generous quantities of the C 19 steroids dehydroepiandrosterone (DHEA) and DHEA-sulphate

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Section: β Hsds (β -Hydroxysteroid Dehydrogenase/ ∆ 5/4 -Isomerases)mentioning

confidence: 99%

Adrenarche – physiology, biochemistry and human disease

Auchus¹,

Rainey

2003

Clinical Endocrinology

258

148

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“…It is unlikely that this anatomical distribution of 17/3-hydroxysteroid (17/3-HSD)l and 20a-hydroxysteroid oxidation/reduction activities, favoring C-17 and C-20 reduction in some tissues and oxidation in others can be accounted for by the redox potential of a given cell. Rather, it is much more likely that this difference in sex steroid hormone synthesis and metabolism is attributable to tissue-specific expression of isozymes that catalyze the 17/-oxidation-reduction of C19-and C18-steroids and the 20a-oxidation-reduction of progesterone, in a manner similar to that now recognized for the 3,6-hydroxysteroid dehydrogenase family of enzymes (10). A number of investigators have deduced, therefore, that there must be multiple 17fi-HSDs, some of which also are capable of C-20a-oxidoreduction.…”

Section: Introductionmentioning

confidence: 99%

17 beta-Hydroxysteroid dehydrogenase type 2: chromosomal assignment and progestin regulation of gene expression in human endometrium.

Casey¹,

Pc²,

Andersson³

1994

J. Clin. Invest.

204

112

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The cDNAs for two separate human 17,B-hydroxysteroid dehydrogenases (17p-HSD) have been isolated and sequenced. The well-studied human placental cytosolic 17wB-HSD (also referred to as estradiol dehydrogenase) preferentially catalyzes the reduction of estrone to estradiol-17/3 and the reduction of the C-20-ketone of progesterone to 20-dihydroprogesterone. This isoform of the enzyme has been referred to as 17j8-HSD type 1 and localized to chromosome 17. A second 17fi-HSD isoform (referred to as type 2) is localized in the endoplasmic reticulum of human trophoblast and is characterized by the preferential oxidation of the C-17fi-hydroxyl group of C18-and C19-steroids and the C-20a-hydroxyl group of 20a-dihydroprogesterone. In this study, we determined the chromosomal localization of human 1713-HSD type 2, the expression of this gene in human endometrium, and the tissue distribution of the mRNA. We found that the human 17,B-HSD type 2 gene is localized on chromosome 16, 16q24. 17/8-HSD type 2 mRNA ( 1.5 kb) was identified in human endometrial tissues by Northern analysis of total RNA (10 ,ug). The highest levels of 17.3-HSD type 2 mRNA were found in endometrial tissues obtained during the mid-to late secretory phase of the ovarian cycle (i.e., during the time of high plasma levels of progesterone). 17fi-HSD type 2 mRNA levels were much greater in glandular epithelium than in the stromal cells isolated from secretory phase endometrium. The levels of 17fi-HSD type 2 mRNA in secretory phase endometrium were approximately one-tenth that in villous trophoblast tissue from human placenta. We did not detect 17fi-HSD type 1 mRNA in endometrial tissue by Northern analysis of total (10 ,.g) RNA. These findings are consistent with the view that the progestinregulated 17(3-HSD of the glandular epithelium of the human endometrium is primarily, if not exclusively, the product of the 17fi-HSD type 2 gene. 17f8-HSD type 2 mRNA

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“…1) (Labrie et al 1992b, Katagiri & Kagawa 1998, and for review see Pikuleva & Waterman 1999). To determine the ability of TReP-132 to regulate Preg transformation towards these groups of steroids, the products formed in NCI-H295 cells following the incubation with [ 3 H]Preg were analyzed.…”

Section: Trep-132 Expression Activates Steroid Synthesis Dependent Onmentioning

confidence: 99%

“…P450c17, which possesses both 17 -hydroxylase and 17,20-lyase activities, catalyzes the first step in the formation of glucocorticoids and C 19 steroids (Zuber et al 1986), while the formation of Prog from Preg is catalyzed by the 3 -HSDII enzyme , Labrie et al 1992b.…”

Section: Introductionmentioning

confidence: 99%

The transcriptional regulating protein of 132 kDa (TReP-132) differentially influences steroidogenic pathways in human adrenal NCI-H295 cells

Gizard

Teissier²,

Dufort³

et al. 2004

Journal of Molecular Endocrinology

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Steroid hormones synthesized from cholesterol in the adrenal gland are important regulators of many physiological processes. It is now well documented that the expression of many genes required for steroid biosynthesis is dependent on the coordinated expression of the nuclear receptor steroidogenic factor-1 (SF-1). However, transcriptional mechanisms underlying the species-specific, developmentally programmed and hormone-dependent modulation of the adrenal steroid pathways remain to be elucidated. Recently, we demonstrated that the transcriptional regulating protein of 132 kDa (TReP-132) acts as a coactivator of SF-1 to regulate human P450scc gene transcription in human adrenal NCI-H295 cells. The present study shows that overexpression of TReP-132 increases the level of active steroids produced in NCI-H295 cells. The conversion of pregnenolone to downstream steroids following TReP-132 expression showed increased levels of glucocorticoids, C 19 steroids and estrogens. Correlating with these data, TReP-132 increases P450c17 activities via the induction of transcript levels and promoter activity of the P450c17 gene, an effect that is enhanced in the presence of cAMP or SF-1. In addition, P450aro activity and mRNA levels are highly induced by TReP-132, whereas 3 -hydroxysteroid dehydrogenase type II and P450c11aldo transcript levels are only slightly modulated. Taken together, these results demonstrate that TReP-132 is a trans-acting factor of genes involved in adrenal glucocorticoid, C 19 steroid and estrogen production.

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Structure and tissue-specific expression of 3ß-hydroxysteroid dehydrogenase/5-ene-4-ene isomerase genes in human and rat classical and peripheral steroidogenic tissues

Cited by 85 publications

References 45 publications

Adrenarche – physiology, biochemistry and human disease

Adrenarche – physiology, biochemistry and human disease

17 beta-Hydroxysteroid dehydrogenase type 2: chromosomal assignment and progestin regulation of gene expression in human endometrium.

The transcriptional regulating protein of 132 kDa (TReP-132) differentially influences steroidogenic pathways in human adrenal NCI-H295 cells

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