Abstract
Objective
Conversion of androstenedione to testosterone, the most potent androgen secreted by the ovary, is carried out by androgenic 17β-hydroxysteroid dehydrogenase (17β-HSD) activity. The molecular basis for this is unclear. We tested the hypothesis that type 5 17β-HSD (17β-HSD5) is responsible for testosterone formation from androstenedione in the human ovary.
Methods
We used primers specific for each type of 17β-HSD to identify quantitatively and directly sequence the polymerase chain reaction products of a human ovary library.
Results
17β-HSD1, 17β-HSD4, and 17β-HSD5 were detected in the library lysate, but not 17β-HSD2 or 17β-HSD3. 17β-HSD5 was the predominant androgenic form of 17β-HSD expressed in human ovary.
Conclusion
These data suggest that 17β-HSD5 may play a major role in testosterone biosynthesis by the human ovary. Further investigation of the regulation of 17β-HSD5 gene expression is warranted with regard to ovarian testosterone secretion in normal and abnormal states of ovarian function, such as polycystic ovary syndrome.
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References
Labrie F, Luu-The V, Lin SX, et al. The key role of 17 beta-hydroxysteroid dehydrogenases in sex steroid biology. Steroids 1997;62:148–58.
Peltoketo H, Isomaa V, Maentausta O, et al. Complete amino acid sequence of human placental 17 beta-hydroxysteroid dehydrogenase deduced from cDNA. FEBS Lett 1988;239:73–7.
The VL, Labrie C, Zhao MF, et al. Characterization of cDNAs for human estradiol 17 beta-dehydrogenase and assignment of the gene to chromosome 17: Evidence of two mRNA species with distinct 5′-termini in human placenta. Mol Endocrinol 1989;3:1301–9.
Wu L, Einstein M, Geissler WM, et al. Expression cloning and characterization of human 17 beta-hydroxysteroid dehydrogenase type 2, a microsomal enzyme possessing 20 alpha-hydroxysteroid dehydrogenase activity. J Biol Chem 1993;268:12964–9.
Casey ML, MacDonald PC, Andersson S. 17 beta-Hydroxy-steroid dehydrogenase type 2: Chromosomal assignment and progestin regulation of gene expression in human endometrium. J Clin Invest 1994;94:2135–41.
Mendonca B, Arnhold I, Bloise W, et al. 17β-Hydroxysteroid dehydrogenase 3 deficiency in women. J Clin Endocrinol Metab 1999;84:802–4.
Geissler WM, Davis DL, Wu L, et al. Male pseudohermaphroditism caused by mutations of testicular 17 beta-hydroxysteroid dehydrogenase 3. Nat Genet 1994;7:34–9.
Stoffel-Wagner B, Watzka M, Steckelbroeck S, et al. Expression of 17 beta-hydroxysteroid dehydrogenase types 1, 2, 3 and 4 in the human temporal lobe. J Endocrinol 1999;160:119–26.
Zhang Y, Word RA, Fesmire S, et al. Human ovarian expression of 17 beta-hydroxysteroid dehydrogenase types 1,2, and 3. J Clin Endocrinol Metab 1996;81:3594–8.
Adamski J, Normand T, Leenders F, et al. Molecular cloning of a novel widely expressed human 80 kDa 17 beta-hydroxysteroid dehydrogenase IV. Biochem J 1995;311:437–43.
Dufort I, Rheault P, Huang XF, et al. Characteristics of a highly labile human type 5 17 beta-hydroxysteroid dehydrogenase. Endocrinology 1999;140:568–74.
Khanna M, Qin K, Wang RW, et al. Substrate specificity, gene structure, and tissue-specific distribution of multiple human 3 alpha-hydroxysteroid dehydrogenases. J Biol Chem 1995;270:20162–8.
Lin HK, Jez JM, Schlegel BP, et al. Expression and characterization of recombinant type 2 3 alpha-hydroxysteroid dehydrogenase (HSD) from human prostate: Demonstration of bifunctional 3 alpha/17 beta-HSD activity and cellular distribution. Mol Endocrinol 1997;11:1971–84.
Qin K, New MI, Cheng KC. Molecular cloning of multiple cDNAs encoding human enzymes structurally related to 3 alpha-hydroxysteroid dehydrogenase. J Steroid Biochem Mol Biol 1993;46:673–9.
Qin K, Khanna M, Cheng KC. Structure of a gene coding for human dihydrodiol dehydrogenase/bile acid-binding protein. Gene 1994;149:357–61.
Adashi EY, Hennebold JD. Single-gene mutations resulting in reproductive dysfunction in women. N Engl J Med 1999;340:709–18.
Harada N, Utsumi T, Takagi Y. Tissue-specific expression of the human aromatase cytochrome P-450 gene by alternative use of multiple exons 1 and promoters, and switching of tissue-specific exons 1 in carcinogenesis. Proc Natl Acad Sci USA 1993;90:11312–6.
Horton R, Tait JF. Androstenedione production and interconversion rates measured in peripheral blood and studies on the possible site of its conversion to testosterone. J Clin Invest 1966;45:301–13.
Bardin C, Lipsett M. Testosterone and androstenedione blood production rates in normal women and women with idiopathic hirsutism or polycystic ovaries. J Clin Invest 1967;46:891–902.
Kirschner MA, Sinhamahapatra S, Zucker IR, et al. The production, origin and role of dehydroepiandrosterone and D5-androstenediol as androgen prehormones in hirsute women. J Clin Endocrinol Metab 1973;37:183–9.
Ehrmann DA, Barnes RB, Rosenfield RL. Polycystic ovary syndrome as a form of functional ovarian hyperandrogenism due to dysregulation of androgen secretion. Endocr Rev 1995;16:322–53.
Rosenfield RL, Barnes RB, Ehrmann DA. Studies of the nature of 17-hydroxyprogesterone hyperresponsiveness to gonadotropin releasing hormone agonist challenge in functional ovarian hypcrandrogenism. J Clin Endocrinol Metab 1994;79:1686–92.
Pittaway DE, Andersen RN, Coleman SA Jr, et al. Human ovarian 17 beta-hydroxysteroid oxidoreductase activity: A comparison of normal and polycystic ovarian tissues. J Clin Endocrinol Metab 1983;56:715–29.
Barbieri R. Human ovarian 17-ketosteroid oxidoreductase: Unique characteristics of the granulosa-luteal cell and stromal enzyme. Am J Obstet Gynecol 1992;166:1117–23.
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This work was supported by USPHS grant no. T32 DK-07011, a gift from Lilly Research Laboratories (KQ), and USPHS grant nos. HD-06308 and RR-00055 (RLR).
The authors thank Dr. Samuel Refetoff for helpful advice.
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Qin, Kn., Rosenfield, R.L. Expression of 17β-Hydroxysteroid Dehydrogenase Type 5 in Human Ovary: A Pilot Study. Reprod. Sci. 7, 61–64 (2000). https://doi.org/10.1177/107155760000700109
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DOI: https://doi.org/10.1177/107155760000700109