Characterization of rat 17β-hydroxysteroid dehydrogenase type 1 gene and mRNA transcripts

Akinola, Lateef; Poutanen, Matti; Peltoketo, Hellevi; Vihko, R.; Vihko, Pirkko

doi:10.1016/s0378-1119(97)00669-0

Cited by 11 publications

(5 citation statements)

References 39 publications

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“…This finding may indicate that testosterone administered to the dam is not delivered to the fetus, but is metabolized or blocked at the placenta [27,44]. Rat placenta does not have aromatase enzyme [45,46] to convert testosterone to estradiol but predominately expresses Δ 4 -reductase and 17β-hydroxysteroid dehydrogenase that metabolizes testosterone to weak androgens such as 5α-androstane-3α-17β-diol [47] and androsterone [27], respectively. Testosterone given to the pregnant rat may be metabolized by the dam, placenta and/or fetus to other androgens, of which androsterone is the most abundant in the fetus, followed by 3α-androstanediol and epiandrosterone [27].…”

Section: Discussionmentioning

confidence: 99%

Prenatal testosterone-induced fetal growth restriction is associated with down-regulation of rat placental amino acid transport

Sathishkumar

Elkins

Chinnathambi

et al. 2011

Reprod Biol Endocrinol

106

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BackgroundExposure of pregnant mothers to elevated concentrations of circulating testosterone levels is associated with fetal growth restriction and delivery of small-for-gestational-age babies. We examined whether maternal testosterone crosses the placenta to directly suppress fetal growth or if it modifies placental function to reduce the capacity for transport of nutrients to the fetus.MethodsPregnant rats were exposed to testosterone propionate (TP; 0.5 mg/kg) by daily subcutaneous injection from gestational days (GD) 15-19. Maternal and fetal testosterone levels, placental nutrient transport activity and expression of transporters and birth weight of pups and their anogenital distances were determined.ResultsThis dose of TP doubled maternal testosterone levels but had no effect on fetal testosterone levels. Maternal daily weight gain was significantly lower only on GD 19 in TP treated dams compared to controls. Placental weight and birth weight of pups were significantly reduced, but the anogenital distance of pups were unaffected by TP treatment. Maternal plasma amino acids concentrations were altered following testosterone exposure, with decreases in glutamine, glycine, tyrosine, serine, proline, and hydroxyproline and increases in asparagine, isoleucine, leucine, lysine, histidine and arginine. In the TP dams, placental system A amino acid transport activity was significantly reduced while placental glucose transport capacity was unaffected. Decreased expression of mRNA and protein levels of slc38a2/Snat2, an amino acid transporter, suggests that reduced transporter proteins may be responsible for the decrease in amino acid transport activity.ConclusionsTaken together, these data suggest that increased maternal testosterone concentrations do not cross the placenta to directly suppress fetal growth but affects amino acid nutrient delivery to the fetus by downregulating specific amino acid transporter activity.

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Section: Discussionmentioning

confidence: 99%

Prenatal testosterone-induced fetal growth restriction is associated with down-regulation of rat placental amino acid transport

Sathishkumar

Elkins

Chinnathambi

et al. 2011

Reprod Biol Endocrinol

106

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“…Two human HSD17B1 promoters result in two 17HSD/KSR1 mRNA forms (Luu-The et al 1990), but apparently only the shorter mRNA type (1·3 kb) is efficiently translated to 17HSD/ KSR1 protein (Miettinen et al 1996). Alternative use of polyadenylation signals, in turn, leads to two rat 17HSD/KSR1 transcripts (Akinola et al , 1998. Instead, HSD17B4 is expressed as a single mRNA species and the protein product is later split to three different functional parts (Leenders et al 1996a).…”

Section: Hsd/ksr Genesmentioning

confidence: 99%

17beta-hydroxysteroid dehydrogenase (HSD)/17-ketosteroid reductase (KSR) family; nomenclature and main characteristics of the 17HSD/KSR enzymes

Peltoketo¹,

Luu‐The²,

Simard³

et al. 1999

Journal of Molecular Endocrinology

274

164

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“…Whereas CYP19 in rodents is found both in the follicle and corpus luteum, two different 17␤HSDs are expressed in a cell-specific manner in the ovary (1). In the follicle, specifically the granulosa cells, 17␤-hydroxysteroid dehydrogenase type 1 (HSD17B1) converts estrone, generated by the conversion of androstendione by CYP19, to estradiol (1,2). HSD17B1 also catalyzes the conversion of androstenedione to testosterone (3), which can be aromatized to estradiol directly.…”

mentioning

confidence: 99%

“…HSD17B1 also catalyzes the conversion of androstenedione to testosterone (3), which can be aromatized to estradiol directly. HSD17B1 was the first to be identified in the follicle characterized and crystallized (2,(4)(5)(6)(7), yet no expression of this enzyme could be detected in the corpus luteum. Despite the fact that the rodent corpus luteum was shown to express CYP19 and able to synthesize estradiol (1,8), the luteal 17␤HSD responsible for converting estrone to estradiol and/or androstenedione to testosterone remained elusive for years.…”

mentioning

confidence: 99%

Prolactin Receptor-Associated Protein/17β-Hydroxysteroid Dehydrogenase Type 7 Gene (Hsd17b7) Plays a Crucial Role in Embryonic Development and Fetal Survival

Shehu¹,

Mao²,

Gibori³

et al. 2008

Molecular Endocrinology

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Our laboratory has previously cloned and purified a protein named PRAP (prolactin receptor-associated protein) that was shown to be a novel 17beta-hydroxysteroid dehydrogenase (HSD) enzyme with dual activity. This enzyme, renamed HSD17B7 or PRAP/17beta-HSD7, converts estrone to estradiol and is also involved in cholesterol biosynthesis. The major site of its expression is the corpus luteum of a great number of species including rodents and humans. To examine the functional significance of HSD17B7 in pregnancy, we generated a knockout mouse model with targeted deletions of exons 1-4 of this gene. We anticipated a mouse with a severe fertility defect due to its inability to regulate estrogen levels during pregnancy. The heterozygous mutant mice are normal in their development and gross anatomy. The females cycle normally, and both male and female are fertile with normal litter size. To our surprise, the breeding of heterozygous mice yielded no viable HSD17B7 null mice. However, we found HSD17B7 null embryo alive in utero on d 8.5 and d 9.5. By d 10.5, the fetuses grow and suffer from severe brain malformation and heart defect. Because the brain depends on in situ cholesterol biosynthesis for its development beginning at d 10, the major cause of fetal death appears to be due to the cholesterol synthetic activity of this enzyme. By ablating HSD17B7 function, we have uncovered, in vivo, an important requirement for this enzyme during fetal development.

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Characterization of rat 17β-hydroxysteroid dehydrogenase type 1 gene and mRNA transcripts

Cited by 11 publications

References 39 publications

Prenatal testosterone-induced fetal growth restriction is associated with down-regulation of rat placental amino acid transport

Prenatal testosterone-induced fetal growth restriction is associated with down-regulation of rat placental amino acid transport

17beta-hydroxysteroid dehydrogenase (HSD)/17-ketosteroid reductase (KSR) family; nomenclature and main characteristics of the 17HSD/KSR enzymes

Prolactin Receptor-Associated Protein/17β-Hydroxysteroid Dehydrogenase Type 7 Gene (Hsd17b7) Plays a Crucial Role in Embryonic Development and Fetal Survival

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