The protein kinase A pathway regulates CYP17 expression and androgen production in the human placenta

Julian C. Escobar, Bruce R. Carr

Research output: Contribution to journalArticle

8 Citations (Scopus)

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 17α- 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.

Original languageEnglish (US)
Pages (from-to)2869-2873
Number of pages5
JournalJournal of Clinical Endocrinology and Metabolism
Volume96
Issue number9
DOIs
StatePublished - Sep 2011

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Steroid 17-alpha-Hydroxylase
Cyclic AMP-Dependent Protein Kinases
Placenta
Androgens
Colforsin
Steroids
Trophoblasts
Estrogens
17-alpha-Hydroxyprogesterone
Messenger RNA
Cell culture
Cell Culture Techniques
Mothers
Pharmacology
Polymerase Chain Reaction
N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

Cite this

The protein kinase A pathway regulates CYP17 expression and androgen production in the human placenta. / Escobar, Julian C.; Carr, Bruce R.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 96, No. 9, 09.2011, p. 2869-2873.

Research output: Contribution to journalArticle

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