Two 17β-hydroxysteroid dehydrogenases (17HSDs) of estradiol biosynthesis: 17HSD type 1 and type 7

Peltoketo, Hellevi; Nokelainen, Pasi; Piao, Yun-shang; Vihko, R.; Vihko, Pirkko

doi:10.1016/s0960-0760(99)00064-3

Cited by 52 publications

(30 citation statements)

References 41 publications

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“…The transformation of testosterone to 4-dione is about 25% of that of E 2 into E 1 . In a recent review, Peltoketo et al (1999) suggest that this enzyme be named type 8 17 -HSD. In addition to the kidney, the Ke6a protein is abundant in the mouse liver and gonads, while the Ke6b form is more specifically expressed in the spleen.…”

Section: Type 8 17 -Hsdmentioning

confidence: 99%

Intracrinology: role of the family of 17 beta-hydroxysteroid dehydrogenases in human physiology and disease

Labrie¹,

Luu‐The²,

Lin³

et al. 2000

Journal of Molecular Endocrinology

258

166

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In women and men, an important proportion of estrogens and androgens are synthesized locally at their site of action in peripheral target tissues. This new field of endocrinology has been called intracrinology. In postmenopausal women, 100% of active sex steroids are synthesized in peripheral target tissues from inactive steroid precursors while, in adult men, approximately 50% of androgens are made locally in intracrine target tissues. The last and key step in the formation of all estrogens and androgens is catalyzed by members of the family of 17 -hydroxysteroid dehydrogenases (17 -HSDs) while different 17 -HSDs inactivate these steroids in the same cell where synthesis takes place. To date, seven human 17 -HSDs have been cloned, sequenced and characterized. The 17 -HSDs provide each cell with the means of precisely controlling the intracellular concentration of each sex steroid according to local needs.

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Section: Type 8 17 -Hsdmentioning

confidence: 99%

Intracrinology: role of the family of 17 beta-hydroxysteroid dehydrogenases in human physiology and disease

Labrie¹,

Luu‐The²,

Lin³

et al. 2000

Journal of Molecular Endocrinology

258

166

View full text Add to dashboard Cite

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“…17HSD1 is known to be expressed in granulosa cells of developing ovarian follicles of probably all mammals [6][7][8] and, in addition, in the syncytiotrophoblast of the placenta in primates and some other species [9,10]. 17HSD1 is thought to be responsible for the preovulatory surge of estradiol arising from the granulosa cells of the dominant follicle and for fetal estradiol supply from the placenta during primate pregnancy [11,12].…”

Section: Introductionmentioning

confidence: 99%

“…Its enzymatic properties as an estrogenic 17HSD were discovered later in mice [15]. Results from experiments with mice and rats clearly indicated a specific role for the maintenance of pregnancy, but maintenance of pregnancy and control of CL function are very different in primates and rodents [12,16]. In rodents, estradiol synthesis takes place exclusively in the CL throughout pregnancy, and the placenta is not a steroidogenic tissue.…”

Section: Introductionmentioning

confidence: 99%

Characterization of 17β-Hydroxysteroid Dehydrogenase Type 7 in Reproductive Tissues of the Marmoset Monkey1

Husen

Adamski

Brüns

et al. 2003

Biology of Reproduction

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In contrast to the known rodent enzymes, the physiological significance of 17␤-hydroxysteroid dehydrogenase type 7 (17HSD7) and its presumed function in reproductive biology is not well understood in primates. As a first step, we recently cloned the complete coding regions of human and marmoset monkey (Callithrix jacchus) 17HSD7 (cj17HSD7). In the present work the complete cDNA of marmoset 17HSD1 (cj17HSD1), including the proximal promoter region, and a partial sequence of marmoset aromatase (cjARO) were sequenced in order to compare the expression of these estradiol synthesizing enzymes with that of 17HSD7 in a primate model and to identify tissues where 17HSD7 might participate in the pathway of estradiol synthesis. The gene structures of cj17HSD1 and cj17HSD7 were determined and proved to be very similar to the human orthologues. Northern hybridization showed that cjARO mRNA seems to be coexpressed preferably with cj17HSD1 in placenta, whereas in other tissues it is expressed in parallel only with cj17HSD7. Especially in corpora lutea, the cj17HSD7 transcript is detectable throughout the luteal phase of the ovarian cycle and increases during pregnancy, in parallel with the transcript of aromatase. Results were confirmed by immunoblots and immunohistochemistry using new polyclonal antisera directed against cj17HSD7 and cjARO protein. The enzymatic conversion of estrone to estradiol was assessed in marmoset corpora lutea. The pattern of coexpression with aromatase supports the hypothesis that luteal 17HSD7 complements placental 17HSD1, ensuring continued estradiol synthesis throughout pregnancy in primates.corpus luteum function, estradiol, female reproductive tract, ovulatory cycle, pregnancy

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“…This includes putative functional variants such as nonsynonymous coding SNPs as well as variants of unknown function in intronic and 59 and 39 untranslated regions. In the case of HSD17B1, there is evidence that several upstream regions participate in the regulation of HSD17B1 expression [28]. All of these lie well within the region of high linkage disequilibrium spanning HSD17B1; hence, common variants in these regulatory regions are accurately predicted by the four htSNPs analyzed here.…”

Section: Discussionmentioning

confidence: 58%

“…Functionally active 17b-HSD-1 is expressed in the testis [26], the primary site of testosterone synthesis. Although initial studies found evidence of HSD17B1 expression in prostate tissue [21,27], more recent studies of prostate cancer cell lines have found small amounts of the longer of the two HSD17B1 transcripts, which does not appear to correlate with 17b-HSD-1 protein levels [28][29][30][31][32].…”

Section: Synopsismentioning

confidence: 93%

Genetic variation in the HSD17B1 gene and risk of prostate cancer

Kraft¹,

Hayes²,

Pharoah³

et al. 2005

PLoS Genet

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Steroid hormones are believed to play an important role in prostate carcinogenesis, but epidemiological evidence linking prostate cancer and steroid hormone genes has been inconclusive, in part due to small sample sizes or incomplete characterization of genetic variation at the locus of interest. Here we report on the results of a comprehensive study of the association between HSD17B1 and prostate cancer by the Breast and Prostate Cancer Cohort Consortium, a large collaborative study. HSD17B1 encodes 17b-hydroxysteroid dehydrogenase 1, an enzyme that converts dihydroepiandrosterone to the testosterone precursor D5-androsterone-3b,17b-diol and converts estrone to estradiol. The Breast and Prostate Cancer Cohort Consortium researchers systematically characterized variation in HSD17B1 by targeted resequencing and dense genotyping; selected haplotype-tagging single nucleotide polymorphisms (htSNPs) that efficiently predict common variants in U.S. and European whites, Latinos, Japanese Americans, and Native Hawaiians; and genotyped these htSNPs in 8,290 prostate cancer cases and 9,367 study-, age-, and ethnicity-matched controls. We found no evidence that HSD17B1 htSNPs (including the nonsynonymous coding SNP S312G) or htSNP haplotypes were associated with risk of prostate cancer or tumor stage in the pooled multiethnic sample or in U.S. and European whites. Analyses stratified by age, body mass index, and family history of disease found no subgroup-specific associations between these HSD17B1 htSNPs and prostate cancer. We found significant evidence of heterogeneity in associations between HSD17B1 haplotypes and prostate cancer across ethnicity: one haplotype had a significant (p , 0.002) inverse association with risk of prostate cancer in Latinos and Japanese Americans but showed no evidence of association in African Americans, Native Hawaiians, or whites. However, the smaller numbers of Latinos and Japanese Americans in this study makes these subgroup analyses less reliable. These results suggest that the germline variants in HSD17B1 characterized by these htSNPs do not substantially influence the risk of prostate cancer in U.S. and European whites.Citation: Kraft P, Pharoah P, Chanock SJ, Albanes D, Kolonel LN, et al. (2005) Genetic variation in the HSD17B1 gene and risk of prostate cancer. PLoS Genet 1(5): e68.

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Two 17β-hydroxysteroid dehydrogenases (17HSDs) of estradiol biosynthesis: 17HSD type 1 and type 7

Cited by 52 publications

References 41 publications

Intracrinology: role of the family of 17 beta-hydroxysteroid dehydrogenases in human physiology and disease

Intracrinology: role of the family of 17 beta-hydroxysteroid dehydrogenases in human physiology and disease

Characterization of 17β-Hydroxysteroid Dehydrogenase Type 7 in Reproductive Tissues of the Marmoset Monkey1

Genetic variation in the HSD17B1 gene and risk of prostate cancer

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