Human 3β-Hydroxysteroid Dehydrogenase/ δ5→4Isomerase from Placenta: Expression in Nonsteroidogenic Cells of a Protein that Catalyzes the Dehydrogenation/Isomerization of C21 and C19 Steroids*

Lorence, Matthew C.; Murry, Barbara A.; Trant, John M.; Mason, J. Ian

doi:10.1210/endo-126-5-2493

Cited by 216 publications

(110 citation statements)

References 9 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

259

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

259

148

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“…Polyclonal rabbit antibodies were raised against: (i) bovine adrenal cholesterol side chain cleavage (SCC) enzyme (M. R. Waterman, Biochemistry Dept, Texas University, Dallas, TX), used at 1 in 100 dilution; (ii) human placental 3␤-hydroxysteroid dehydrogenase (3␤-HSD; J. I. Mason; see Lorence et al, 1990), used at 1 in 100 dilution; (iii) pig testicular 17␣-hydroxylase (A. Payne; see Hales et al, 1987), used at 1 in 100 dilution; and (iv) human placental aromatase (N. Harada; see Naganuma et al, 1990), used at 1 in 100 dilution.…”

Section: Steroid Synthesis Enzyme Antibodiesmentioning

confidence: 99%

Developmental changes in localization of steroid synthesis enzymes in camelid placenta

Wooding

Öztürk²,

Skidmore³

et al. 2003

Reproduction

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The uninucleate trophoblast of epitheliochorial camelid placenta produces multinucleate giant cells starting between day 30 and day 35 of pregnancy. The giant cells are found scattered along the trophoblast at similar frequency throughout gestation. Light microscope immunocytochemistry indicates that the four steroid synthesis enzymes (cholesterol side chain cleavage, 3␤-hydroxysteroid dehydrogenase, 17␣-hydroxylase and aromatase) are present in all uninucleate trophoblast cells between day 14 and day 30 of pregnancy, but are found only in the giant cells once they are established, and that this localization persists until term. The giant cells show massive amounts of smooth endoplasmic reticulum and numerous small mitochondria, again as has been shown in other steroidproducing cells. As progesterone from the corpus luteum is necessary throughout gestation in camels, the capacity for oestrogen production by the trophoblast presumably has an important role, but one limited mostly to the immediate vicinity of the fetomaternal interface.

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“…The uPA cDNA fragment from HindIII to SspI, containing 75 bp of 5Ј untranslated and 600 bp of 3Ј untranslated sequence, was inserted into the adenovirus construction plasmid, pACskCMV2. This plasmid contains the left end of adenovirus type 5 including the origin of replication and packaging sequences (np 1-454), the SV40 ori/hGH terminator from pCMV5, 37 a polylinker to facilitate cDNA insertion, the CMV promoter and flanking adenovirus sequences (np 3334-5779) serving as the target for homologous recombination. It was kindly provided by Joseph Alcorn of UT Southwestern Medical Center (Dallas, TX, USA).…”

Section: Constructionmentioning

confidence: 99%

Reduction of tumor cell migration and metastasis by adenoviral gene transfer of plasminogen activator inhibitors

et al. 1999

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Recombinant adenoviral vectors expressing u-PA, t-PA, virus expressing either PAI-1 or PAI-2 before implantation PAI-1 and PAI-2 were employed to correlate the significantly reduced the incidence of lung metastasis by expression of components of the fibrinolytic system with 60% compared with control virus. However, only PAI-2 the invasiveness of HT 1080 tumor cells. Migration through reduced the incidence of lung and brain metastasis followTranswell inserts in vitro in the presence of plasminogen ing liver gene transfer. Although PAI gene transfer by either was increased up to 22% by overexpression of u-PA, route reduced primary tumor size, it had little effect on whereas t-PA had no effect. Gene transfer of PAI-1 or PAItumor vascularization or host survival. The migratory and 2 both reduced migration in a dose-dependent manner by metastatic phenotype of HT 1080 tumor cells is thus up to 43% with PAI-1 and 29% with PAI-2. Two routes of directly dependent on u-PA expression levels and can be gene transfer were used to alter metastasis of subcutanealtered by gene transfer of u-PA or plasminogen activator ously implanted HT 1080 cells expressing firefly luciferase inhibitors. in nude mice. Infection of cultured tumor cells with adeno-

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Human 3β-Hydroxysteroid Dehydrogenase/ δ5→4Isomerase from Placenta: Expression in Nonsteroidogenic Cells of a Protein that Catalyzes the Dehydrogenation/Isomerization of C21 and C19 Steroids*

Cited by 216 publications

References 9 publications

Adrenarche – physiology, biochemistry and human disease

Adrenarche – physiology, biochemistry and human disease

Developmental changes in localization of steroid synthesis enzymes in camelid placenta

Reduction of tumor cell migration and metastasis by adenoviral gene transfer of plasminogen activator inhibitors

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