Evidence map›Paper›PMID 25868050›Full record

ArticleEndocrinology2015

Bone Morphogenetic Protein-4 (BMP4): A Paracrine Regulator of Human Adrenal C19 Steroid Synthesis.

Juilee Rege, Hiromi Koso Nishimoto, Koshiro Nishimoto, Raymond J Rodgers, Richard J Auchus, William E Rainey

Open access · greenAbstract read

In one paragraph

Article in Endocrinology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it

0cells of the map it votes in

12citing papers in PubMed, 1 pooled it

1.7field-weighted citation impact, top 16% of its field

1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.

Associations Between Follicular Fluid Biomarkers and IVF/ICSI Outcomes in Normo-Ovulatory Women-A Systematic Review.Biomolecules · 2025
Pooled it
Discovery of RXFP2 genetic association in resistant hypertensive men and RXFP2 antagonists for the treatment of resistant hypertension.Scientific reports · 2024
Article
Normal and Premature Adrenarche.Endocrine reviews · 2021
Review
Transcriptomic Response Dynamics of Human Primary and Immortalized Adrenocortical Cells to Steroidogenic Stimuli.Cells · 2021
Article
Molecular and Electrophysiological Analyses of ATP2B4 Gene Variants in Bilateral Adrenal Hyperaldosteronism.Hormones & cancer · 2020
Article
Human cytochrome P450 enzymes 5-51 as targets of drugs and natural and environmental compounds: mechanisms, induction, and inhibition - toxic effects and benefits.Drug metabolism reviews · 2018
Review
Tissue-specific regulation of BMP signaling byeLife · 2017
Article
Clinical significance linked to functional defects in bone morphogenetic protein type 2 receptor, BMPR2.BMB reports · 2017
Article
Molecular Mechanisms of Stem/Progenitor Cell Maintenance in the Adrenal Cortex.Frontiers in endocrinology · 2017
Review
The Pathogenesis of Polycystic Ovary Syndrome (PCOS): The Hypothesis of PCOS as Functional Ovarian Hyperandrogenism Revisited.Endocrine reviews · 2016 · on this map
Review
Impaired 17,20-Lyase Activity in Male Mice Lacking Cytochrome b5 in Leydig Cells.Molecular endocrinology (Baltimore, Md.) · 2016
Article
Functional Zonation of the Adult Mammalian Adrenal Cortex.Frontiers in neuroscience · 2016
Review

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 2 countries.

Juilee RegeDepartment of Molecular and Integrative Physiology (J.R., H.K.N., K.N., W.E.R.), and Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan (R.J.A.), Ann Arbor, Michigan 48109-5622; and School of Pediatrics and Reproductive Health (R.J.R.), Robinson Research Institute, University of Adelaide, South Australia 5005, Australia.

Hiromi Koso NishimotoDepartment of Molecular and Integrative Physiology (J.R., H.K.N., K.N., W.E.R.), and Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan (R.J.A.), Ann Arbor, Michigan 48109-5622; and School of Pediatrics and Reproductive Health (R.J.R.), Robinson Research Institute, University of Adelaide, South Australia 5005, Australia.

Koshiro NishimotoDepartment of Molecular and Integrative Physiology (J.R., H.K.N., K.N., W.E.R.), and Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan (R.J.A.), Ann Arbor, Michigan 48109-5622; and School of Pediatrics and Reproductive Health (R.J.R.), Robinson Research Institute, University of Adelaide, South Australia 5005, Australia.

Raymond J RodgersDepartment of Molecular and Integrative Physiology (J.R., H.K.N., K.N., W.E.R.), and Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan (R.J.A.), Ann Arbor, Michigan 48109-5622; and School of Pediatrics and Reproductive Health (R.J.R.), Robinson Research Institute, University of Adelaide, South Australia 5005, Australia.

Richard J AuchusDepartment of Molecular and Integrative Physiology (J.R., H.K.N., K.N., W.E.R.), and Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan (R.J.A.), Ann Arbor, Michigan 48109-5622; and School of Pediatrics and Reproductive Health (R.J.R.), Robinson Research Institute, University of Adelaide, South Australia 5005, Australia.

William E RaineyDepartment of Molecular and Integrative Physiology (J.R., H.K.N., K.N., W.E.R.), and Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan (R.J.A.), Ann Arbor, Michigan 48109-5622; and School of Pediatrics and Reproductive Health (R.J.R.), Robinson Research Institute, University of Adelaide, South Australia 5005, Australia.

Michigan Medicine · USUniversity of Adelaide · AUUniversity of Michigan–Ann Arbor · US

Funding

Pilot and Feasibility (P and F) ProgramP30DK089503 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI RANDY J SEELEY · 2010 to 2026

$20.3M

MECHANISMS LEADING TO ADRENAL ZONATIONR01DK043140 · NIDDK · UNIVERSITY OF TEXAS SW MED CTR/DALLAS · PI William E Rainey · 1999 to 2026

$7.2M

Molecular Mechanisms of AdrenarcheR01DK069950 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI RAINEY, WILLIAM E · 2005 to 2019

$4.4M

MECHANISMS LEADING TO ADRENAL ZONATIONR29DK043140 · NIDDK · UNIVERSITY OF TEXAS SW MED CTR/DALLAS · PI RAINEY, WILLIAM E · 1994 to 1998

–

NIDDK NIH HHS DK069950NIDDK NIH HHS DK089503NIDDK NIH HHS DK43140NIDDK NIH HHS P30 DK089503NIDDK NIH HHS R01 DK043140NIDDK NIH HHS R01 DK069950

6 · The paper itself

Abstract

Bone morphogenetic proteins (BMPs) comprise one of the largest subgroups in the TGF-β ligand superfamily. We have identified a functional BMP system equipped with the ligand (BMP4), receptors (BMP type II receptor, BMP type IA receptor, also called ALK3) and the signaling proteins, namely the mothers against decapentaplegic homologs 1, 4, and 5 in the human adrenal gland and the human adrenocortical cell line H295R. Microarray, quantitative RT-PCR, and immunohistochemistry confirmed that BMP4 expression was highest in the adrenal zona glomerulosa followed by the zona fasciculata and zona reticularis. Treatment of H295R cells with BMP4 caused phosphorylation of the mothers against decapentaplegic and a profound decrease in synthesis of the C19 steroids dehydroepiandrosterone (DHEA), DHEA sulfate, and androstenedione. Administration of BMP4 to cultures of H295R cells also caused a profound decrease in the mRNA and protein levels of 17α-hydroxylase/17,20-lyase (CYP17A1 and P450c17, respectively) but no significant effect on the mRNA levels of cholesterol side-chain cleavage cytochrome P450 (CYP11A1) or type 2 3β-hydroxysteroid dehydrogenase (HSD3B2). Furthermore, Noggin (a BMP inhibitor) was able to reverse the negative effects of BMP4 with respect to both CYP17A1 transcription and DHEA secretion in the H295R cell line. Collectively the present data suggest that BMP4 is an autocrine/paracrine negative regulator of C19 steroid synthesis in the human adrenal and works by suppressing P450c17.

Indexed as

Adrenal CortexAdrenal GlandsAndrostenedioneBone Morphogenetic Protein 4Bone Morphogenetic Protein Receptors, Type IBone Morphogenetic Protein Receptors, Type IICell LineCholesterol Side-Chain Cleavage EnzymeDehydroepiandrosteroneDehydroepiandrosterone SulfateGene Expression ProfilingHumansParacrine CommunicationProgesterone ReductaseReverse Transcriptase Polymerase Chain ReactionRNA, Messenger3 beta-hydroxysteroid dehydrogenase type IIAndrostenedioneBMP4 protein, humanBone Morphogenetic Protein 4Bone Morphogenetic Protein Receptors, Type IBone Morphogenetic Protein Receptors, Type IICholesterol Side-Chain Cleavage EnzymeCYP17A1 protein, humanDehydroepiandrosteroneDehydroepiandrosterone SulfateProgesterone ReductaseRNA, MessengerSmad1 ProteinSMAD1 protein, humanSmad4 ProteinSMAD4 protein, humanSmad5 ProteinSMAD5 protein, humanSteroid 17-alpha-Hydroxylase

Identifiers

PMID25868050

DOI10.1210/en.2014-1942

PMCPMC4475723

OpenAlexW2125696194

What OpenQuestion holds

Textmetadata

Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.