title: A time-course regulatory and kinetic expression study of steroid metabolizing enzymes by calcitriol in primary cultured human placental cells.
abstract: 1,25-dihydroxivitamin D3(calcitriol), is a secoesteroid involved in several placental functions. In particular, we and others showed that calcitriol regulates peptides, proteins, cytokines and hormones production in human trophoblastic cells. On the other hand, calcitriol modifies the activity and expression of some steroidogenic enzymes, a process that is considered tissue-specific. However, the effects of calcitriol on the expression of enzymes involved in the synthesis of sex steroids in placental tissue have not yet been entirely studied. The aim of the present study was to investigate the effects of calcitriol upon gene expression of several steroid enzymes such as cytochrome P450scc (CYP11A1), type 1 3β-hydroxysteroid dehydrogenase(3β-HSDI), 17β-HSD3, 17α-hydroxylase/17,20 lyase (CYP17A1) and aromatase (CYP19A1) in primary cultures of human placental cells. Cell cultures were performed using placentas obtained immediately after delivery by caesarean section from normotensive healthy women and calcitriol effects were evaluated, at level of transcription, by qPCR. The results showed that: 1) from basal expression values of the five genes studied, 3β-HSDI was the most expressed gene (P<0.05); 2) basal expression of all enzymes was significantly higher in cultured syncytiotrophoblast than in cytotrophoblasts (P<0.05); 3) the presence of calcitriol in cultured trophoblast cells generally resulted in a stimulatory effect of CYP11A1, CYP19A1 and 17β-HSD3 gene expression at 3h of treatment whereas 3β-HSDI was induced at 6h (P<0.05). However, a time-dependent variable was also observed; 4) protein expression of CYP11A1 and 3β-HSDI were not modified significantly by calcitriol, however that of CYP19A1 was regulated in similar fashion as gene expression. In conclusion, calcitriol affected in a time-dependent manner the expression of steroids metabolizing enzymes in human placental cell cultures.
authors.affiliation: Departamento de Biología de la Reproducción, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Av. Vasco de Quiroga No. 15, Col. Belisario Domínguez, Sección XVI, México, D.F. 14080, Mexico.
authors.forename: Nancy
authors.initials: N
authors.lastname: Noyola-Martínez
authors.affiliation: Departamento de Biología de la Reproducción, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Av. Vasco de Quiroga No. 15, Col. Belisario Domínguez, Sección XVI, México, D.F. 14080, Mexico.
authors.forename: Ali
authors.initials: A
authors.lastname: Halhali
authors.affiliation: Departamento de Inmunobioquímica, Instituto Nacional de Perinatología Isidro Espinosa de los Reyes, Montes Urales No. 800, Miguel Hidalgo 11000, México, D.F., Mexico.
authors.forename: Verónica
authors.initials: V
authors.lastname: Zaga-Clavellina
authors.affiliation: Departamento de Biología de la Reproducción, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Av. Vasco de Quiroga No. 15, Col. Belisario Domínguez, Sección XVI, México, D.F. 14080, Mexico.
authors.forename: Andrea
authors.initials: A
authors.lastname: Olmos-Ortiz
authors.affiliation: Departamento de Biología de la Reproducción, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Av. Vasco de Quiroga No. 15, Col. Belisario Domínguez, Sección XVI, México, D.F. 14080, Mexico.
authors.forename: Fernando
authors.initials: F
authors.lastname: Larrea
authors.affiliation: Departamento de Biología de la Reproducción, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Av. Vasco de Quiroga No. 15, Col. Belisario Domínguez, Sección XVI, México, D.F. 14080, Mexico. Electronic address: barrera1912@gmail.com.
authors.forename: David
authors.initials: D
authors.lastname: Barrera
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D001141:Aromatase / Q000378:metabolism; D002117:Calcitriol / Q000737:chemistry*; D002454:Cell Differentiation; D002478:Cells, Cultured; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism; D013256:Steroids / Q000378:metabolism*; D013997:Time Factors; D014327:Trophoblasts / Q000378:metabolism*
chemical_list: D012739:Gonadal Steroid Hormones; D013256:Steroids; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase; D001141:Aromatase; C561410:CYP19A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme; D002117:Calcitriol
keywords: Calcitriol; Cytochromes; Hydroxysteroid dehydrogenases; Placenta; Trophoblast