Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q7LGC8 (HSD)
 3,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The placenta is the primary source of estrogens and progesterone during pregnancy. Because pregnant diabetic women are reported to have lower serum estrogen and higher progesterone levels than nondiabetic pregnant women, and placental insulin-like growth factor II (IGF-II) production may be elevated during diabetic pregnancy, the role of IGF-II in the regulation of human cytotrophoblastic aromatase, 3 beta-hydroxysteroid dehydrogenase (3 beta HSD), and P450 cholesterol side-chain cleavage (P450scc) enzyme activities was studied. Incubation of cytotrophoblasts with IGF-II for 24 h significantly diminished the ability of these cells to convert androstenedione to estrogens by 92.3 +/- 6.6 (SE)%. IGF-II could suppress aromatase activity at a concentration as low as 2.0 ng/ml. Preincubation of cells with either insulin, IGF-I, or a monoclonal anti-IGF-I receptor antibody did not alter IGF-II's potent inhibitory effect. Treatment with mannose 6-phosphate alone also resulted in significant suppression of aromatase activity, and concurrent treatment with both mannose 6-phosphate and IGF-II resulted in greater inhibition than with either agent alone. These observations suggest that IGF-II suppresses aromatase activity by activation of its own specific receptor. In contrast, incubation of cytotrophoblasts with IGF-II for 24 h significantly increased the 3 beta HSD activity (as determined by the conversion of pregnenolone to progesterone) and P450scc activity (as determined by the conversion of 25-hydroxycholesterol to progesterone) of these cells. IGF-II's ability to stimulate these enzymatic processes was found to be comparable in magnitude to that of IGF-I. IGF-II-stimulated 3 beta HSD activity was completely inhibited by concurrent treatment with either actinomycin D or cycloheximide, suggesting that new mRNA and protein synthesis are required for IGF-II to exert its stimulatory effect. These studies indicate that IGF-II is a potent inhibitor of human cytotrophoblastic aromatase activity in vitro. In addition, IGF-II can stimulate cytotrophoblastic 3 beta HSD and P450scc activities. Since placental IGF-II production in pregnant diabetic women may be augmented, these observations may help explain the lower serum estrogen and higher progesterone levels associated with pregnancy in the diabetic patient.
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PMID:Insulin-like growth factor II is a potent inhibitor of the aromatase activity of human placental cytotrophoblasts. 222

The placenta is the primary source of progesterone during pregnancy. Because pregnant diabetic women are reported to have higher serum progesterone levels than nondiabetic pregnant women, we studied the roles of insulin and insulin-like growth factor-I (IGF-I) in the regulation of human cytotrophoblastic 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) activity. Incubation of cytotrophoblasts with insulin or IGF-I for 24 h significantly increased the ability of these cells to convert pregnenolone to progesterone by 75.8 +/- 16.5% (+/- SE) and 65.4 +/- 12.7%, respectively. Treatment with either insulin or IGF-I did not alter cytotrophoblastic production of 20 alpha-hydroxypregn-4-en-3-one (the primary metabolite of progesterone), thus demonstrating that these peptides increased progesterone synthesis (i.e. 3 beta HSD activity) rather than decreased progesterone catabolism. Insulin and IGF-I stimulated 3 beta HSD activity at concentrations as low as 50 and 10 ng/ml, respectively. Insulin- and IGF-I-stimulated 3 beta HSD activities were completely inhibited by concurrent treatment with either actinomycin-D or cycloheximide, suggesting that new mRNA and protein synthesis are required for these peptides to exert their effects. Blockade of the IGF-I receptor of cytotrophoblasts with alpha IR-3, a monoclonal anti-IGF-I receptor antibody, prevented the stimulation of 3 beta HSD activity by IGF-I, but did not alter insulin's stimulatory effect. Thus, the two hormones can each stimulate 3 beta HSD activity via activation of their respective receptors. These studies indicate that insulin and IGF-I can regulate human cytotrophoblastic 3 beta HSD activity in vitro. Since pregnant diabetic women manifest peripheral hyperinsulinemia, and IGF-I levels in fetal cord sera from diabetic pregnancies may be elevated, these observations may help explain the elevated serum progesterone levels associated with pregnancy in the diabetic patient.
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PMID:Insulin and insulin-like growth factor-I stimulate the 3 beta-hydroxysteroid dehydrogenase activity of human placental cytotrophoblasts. 255 37

Environmental anti-androgens are increasingly being recognized as potential contributing factors in the chemically induced feminization of wild fish because, by blocking androgen action, they can produce phenotypic effects similar to environmental estrogens. The molecular mechanisms by which anti-androgens and estrogens exert feminizing effects, however, have not been systematically compared. Using a targeted approach, we profiled the expression responses of a suite of 22 genes involved in reproduction, growth and development (processes controlled by androgens and estrogens) in the liver and gonad in adult male and female fathead minnow (Pimephales promelas) exposed to the model anti-androgen flutamide and the model synthetic estrogen 17alpha-ethinylestradiol (EE(2)). Both flutamide (320 microg/L) and EE(2) (10ng/L) produced phenotypic effects indicative of feminization (induction of plasma vitellogenin, reduced gonadosomatic index, and reduced secondary sex characters), although for the chosen test concentrations EE(2) was the more potent. For the genes studied, flutamide and EE(2) produced distinct expression profiles, suggesting that they largely operate via distinct molecular mechanisms. As examples, in liver EE(2) (but not flutamide) exposure up-regulated estrogen receptor (ER) alpha mRNA, whereas flutamide exposure increased ERbeta and ERgamma mRNAs in males and resulted in decreased androgen receptor (AR) mRNA in females. In the testis, flutamide up-regulated genes coding for enzymes involved in androgen biosynthesis (cytochrome P450 17 [CYP17] and 11beta-hydroxysteroid dehydrogenase [11beta-HSD]) implying an inhibitory action on androgen negative feedback pathways. EE(2), in contrast, inhibited the expression of enzymes involved in androgen biosynthesis (CYP17, 11beta-HSD and 17beta-hydroxysteroid dehydrogenase [17beta-HSD]). There were also some commonalities in the molecular mechanisms of flutamide and EE(2) action, including the down-regulation of gonadal sex steroid receptor expression (gonadal AR and ovarian ERalpha), increased expression of genes coding for estrogen-producing enzymes (cytochrome P450 19A and B [CYP19A and CYP19B]), decreased expression of genes involved in testis differentiation (anti-Mullerian hormone [AMH] and doublesex and mab-3 related transcription factor 1 [DMRT1]), and decreased expression of hepatic genes which mediate wider physiological processes such as somatic growth (growth hormone [GH], GH receptor [GHR], insulin-like growth factor-I [IGF-I], IGF-I receptor [IGF-IR], thyroid hormone receptor alpha [TRalpha] and beta [TRbeta]).
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PMID:Gene expression profiles revealing the mechanisms of anti-androgen- and estrogen-induced feminization in fish. 1722 21

The present study was aimed to investigate the mechanism underlying the influence of maternal low-protein (LP) diet on offspring growth in the chicken. One hundred and twenty Chinese inbred Langshan breeder hens were allocated randomly into two groups fed diets containing low (10%, LP) or normal (15%) crude protein levels. Low dietary protein did not affect the body weight of hens, but significantly decreased the laying rate and egg weight. The yolk leptin content was significantly lower in eggs laid by LP hens, while no differences were detected for yolk contents of corticosterone, tri-iodothyronine (T3) or thyroxine. Despite significantly lower hatch weight, the LP offspring demonstrated obviously higher serum T3 concentration, which is in accordance with the faster post-hatch growth rate achieving significantly heavier body weight and pectoralis major muscle weight 4 weeks post-hatching. Expression of 20-hydroxysteroid dehydrogenase (20-HSD) mRNA in the yolk-sac membrane was significantly down-regulated at embryonic day 14, whereas that of transthyretin and leptin receptor (LepR) was not altered. Moreover, hypothalamic expression of 20-HSD, glucocorticoid receptors, thyrotropin-releasing hormone and LepR mRNA was significantly up-regulated in the LP group compared with their control counterparts. In the pectoralis major muscle, significantly higher expression of insulin-like growth factor (IGF)-I and IGF-I receptor mRNA was observed in LP embryos. The present study provides evidence that maternal LP diet programmes post-hatch growth of the offspring. The associated alterations in yolk leptin deposition as well as in yolk-sac membrane, fetal hypothalamus and muscle gene expression may be involved in mediating such programming effect in the chicken.
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PMID:Maternal low-protein diet programmes offspring growth in association with alterations in yolk leptin deposition and gene expression in yolk-sac membrane, hypothalamus and muscle of developing Langshan chicken embryos. 1926 47