High impact information on Akr1c18

• In dimethylbenz(a)anthracene-induced tumor tissue, high 5 alpha-reductase and 20 alpha-hydroxysteroid dehydrogenase activities and somewhat lower 3 alpha-hydroxysteroid dehydrogenase and 6 alpha-hydroxylase activities were found [1].
• Stimulation of progestin production by EGF appears to be the result of an increase in pregnenolone biosynthesis as well as increases in the activities of 20 alpha-hydroxysteroid dehydrogenase and 3 beta-hydroxysteroid dehydrogenase/isomerase [2].
• The EGF enhancement of FSH-stimulated progestin production appears to be the result of synergistic increases in pregnenolone biosynthesis and 20 alpha-hydroxysteroid dehydrogenase activity, resulting in substantial increases in 20 alpha-hydroxypregn-4-en-3-one but not progesterone production [2].
• In contrast, prolactin (PRL) treatment of FSH-primed granulosa cells resulted in an 88% decrease in 20 alpha-hydroxysteroid dehydrogenase activity as compared to untreated controls [3].
• Furthermore, incubation of granulosa cells for 2 days with GnRH alone resulted in a 2.7-fold increase in 20 alpha-hydroxysteroid dehydrogenase activity, as compared to untreated controls [3].

Biological context of Akr1c18

• The sequence of peptides derived from the purified protein was found in the translated sequence of the open reading frame. cDNA and amino acid sequence indicate that the rat ovarian 20 alpha HSD belongs to the aldo-keto reductase family of enzymes [4].
• We conclude from these observations that luteal regression is a more complex phenomenon than the regulation of a single enzyme, 20 alpha-hydroxysteroid dehydrogenase, and may involve regulation of both the synthesis and degradation of progesterone [5].
• They were killed at intervals during the last 96 h preceding the normal time for onset of parturition, and differences in plasma progesterone, oestradiol-17 beta and ovarian 20 alpha-hydroxysteroid dehydrogenase were assessed [6].
• Active-site directed inactivation of rat ovarian 20 alpha-hydroxysteroid dehydrogenase [7].
• The 20 alpha-hydroxysteroid dehydrogenase activity which was undetectable in untreated rats, rose to 330 pmol 60 h after PMSG, 8 h before ovulation [8].

Anatomical context of Akr1c18

• In addition, the in vitro transcription-translation product produced by Xenopus oocytes showed 20 alpha-HSD activity and Northern-blotting analysis revealed that the ovaries from normal adult rats contained a 1.2 kb mRNA [9].
• Treatment with follicle-stimulating hormone (FSH) increased the 20 alpha-hydroxysteroid dehydrogenase activity of granulosa cells to 1.3-fold of the control value [3].
• In agreement, with previously reported histochemical evidence, an increase in 20 alpha-OH-SDH activity was observed in isolated corpora lutea, but not in the non-luteal compartment of the ovary [5].
• 20 alpha HSD activity of luteal cells (from midpseudopregnant rats), which had been suppressed by PRL in vivo, increased when the cells were cultured for 48 h without PRL addition [10].
• The activities of 20 alpha-hydroxysteroid dehydrogenase and NADPH-linked 3 alpha-hydroxysteroid dehydrogenase were found mainly in the cytosol fractions of the tumor and the normal tissue [11].

Associations of Akr1c18 with chemical compounds

• We report the isolation and characterization of a full length cDNA encoding rat 20 alpha hydroxysteroid dehydrogenase derived from rat corpus luteum RNA [4].
• The granulosa cells obtained from hypophysectomized, estrogen-treated rats were treated with various hormones in vitro and 20 alpha-hydroxysteroid dehydrogenase activity determined by measuring the conversion of radiolabeled 20 alpha-hydroxy-pregn-4-en-3-one to progesterone [3].
• Rat ovarian 20 alpha-hydroxysteroid dehydrogenase plays a pivotal role in leuteolysis and parturition by catalysing the reduction of progesterone to give the progestationally inactive steroid 20 alpha-hydroxyprogesterone [7].
• The inhibition of either 11beta HSD1 or 11beta HSD2 significantly lowered testosterone production in the presence of CORT [12].
• The vinyl ketone inactivates rat ovarian 20 alpha-hydroxysteroid dehydrogenase, semi-purified by poly(L-lysine)-agarose column chromatography, in a rapid time-dependent manner [7].

Regulatory relationships of Akr1c18

• Thus, Prl and the beta 2-agonist stimulate progesterone production in granulosa cells by increasing pregnenolone production and 3 beta-HSD activity as well as by decreasing 20 alpha-HSD activity, while hCG stimulates progesterone production by increasing pregnenolone production and 3 beta-HSD activity [13].
• IGF-I enhanced FSH-stimulated 20 alpha-HSD activity and transcripts (2.3-fold and 1.8-fold, respectively) and increased the basal levels of 20 alpha-HSD transcripts (3-fold) [14].

Other interactions of Akr1c18

• Prolactin reduced markedly 20 alpha HSD mRNA expression [4].
• Furthermore, the suppressive effect of PRL on 20 alpha HSD activity was significantly attenuated by anti-TGF beta antibody [10].
• The administration of the cyclooxygenase inhibitor, diclofenac (1.3 mg/kg), on days 17-19 of pregnancy to RU486-treated rats, delayed abortion and the duration of delivery, and prevented the decrease in 3 beta-HSD and the increase in 20 alpha-HSD activities observed 58 h after antiprogesterone treatment [15].
• Since PGF2 alpha-receptor content does not coincide with the increase in enzyme activity (maximal receptor content preceded maximal enzyme activity by about 6 days), PGF2 alpha may not be the only direct factor responsible for the induction of ovarian 20 alpha-OH-SDH, to terminate luteal function [16].

Analytical, diagnostic and therapeutic context of Akr1c18

• Real-time PCR showed a 6-fold enrichment of 11beta HSD2 mRNA in these cells, compared with whole testis and that the amount of 11beta HSD2 message was about 1000-fold lower, compared with 11beta HSD1 [12].
• Subcutaneous administration of four doses of 10 microgram ovine LH (oLH) at 0800, 0900, 1000 and 1100 h on day 19 of pregnancy induced a decrease in the activity of the enzyme 3 beta-HSD 24 and 48 h after treatment and an increase in luteal 20 alpha-HSD activity 48 h after oLH treatment when compared with control rats [17].
• Molecular cloning and characterization of the rat ovarian 20 alpha-hydroxysteroid dehydrogenase gene [18].
• However, receptor concentration and 20 alpha-hydroxysteroid dehydrogenase induction by hysterectomy was not affected by indomethacin, indicating that these events are probably not related to prostaglandin withdrawal [19].
• Purification of rat ovary 20 alpha-hydroxysteroid dehydrogenase by affinity chromatography [20].

References