NDLI: The protein kinase a pathway regulates CYP17 expression and androgen production in the human placenta.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Carr, Bruce R. Escobar, Julian C.
Description	Country affiliation: United States Author Affiliation: Escobar JC ( Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75235-9032, USA.)
Abstract	BACKGROUND: Our previous work demonstrated that the human placenta expresses CYP17 and is capable of de novo production of C-19 steroids; thus, it has intrinsic capacity to generate estrogens without fetal or maternal steroid precursors. OBJECTIVE: Our objective was to elucidate the regulation of CYP17 expression and androgen production in the human trophoblasts. METHODS: Fresh placentas and JEG-3 cells were used for all experiments. CYP17 mRNA analysis was performed via RT-PCR, and steroid products were quantified using RIA. To assess protein kinase A (PKA) pathway involvement, a pharmacological approach was used with forskolin (FSK) (10 µM), an activator, and H89 (10 µM), an inhibitor of the PKA pathway. RESULTS: FSK treatment amplified CYP17 mRNA levels in both cell types when compared with basal, with levels increasing over time, peaking at 72 h, and appearing more robust in primary cells; this difference ranged from 2- to 10-fold and was statistically significant at all time points. Meanwhile, H89 reduced CYP17 levels and blunted the effect of FSK when the treatments were combined. Similarly, FSK treatment significantly increased 17 -hydroxyprogesterone concentration in both cell cultures, and H89 blunted that effect as well. CONCLUSIONS: We confirm again that the human trophoblast expresses CYP17 and is able to generate estrogen precursors. We demonstrate that this process is regulated, at least in part, by the cAMP/PKA pathway.
ISSN	0021972X
e-ISSN	19457197
Journal	The Journal of Clinical Endocrinology & Metabolism
Issue Number	9
Volume Number	96
Language	English
Publisher	Oxford University Press
Publisher Date	2011-09-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Androgens Biosynthesis Cyclic Amp-dependent Protein Kinases Metabolism Placenta Signal Transduction Physiology Steroid 17-alpha-hydroxylase Cell Line Cells, Cultured Genetics Cytology Pregnancy Discipline Endocrinology Discipline Metabolism
Content Type	Text
Resource Type	Article
Subject	Biochemistry (medical) Endocrinology, Diabetes and Metabolism Clinical Biochemistry Biochemistry Endocrinology

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