Editorial: What's in a Name, or the Impact of Misnomers in Endocrine Research

The simplest definition of the word “misnomer” is that of a wrong name or inappropriate designation for a person, a place, or an object. Alternatively, in the case that interests us in this editorial, it can be a gene or its gene product. In everyday life, the use of misnomers, such as referring to a small meteorite entering the earth atmosphere as a “shooting star,” often has no practical consequence. In fact, misnomers such as this example can add a dose of poetry in our lives, allowing us to dream of distant universes for a brief moment. However, in medicine, the use of misnomers to identify a symptom or a disease can have more serious consequences, such as misdiagnosis or incorrect treatments, even by well-trained physicians. A quick search of PubMed yields a long list of such occurrences that includes, for example, the misnomer “lupus anticoagulant,” a coagulation inhibitor originally identified in patients with systemic lupus erythematosus, but its presence is actually associated with thromboembolic events that may strike in otherwise healthy individuals (1). In medical research, the consequences of using misnomers might be less dire but, nonetheless, can lead some misguided investigators to pursue research projects in the wrong direction, misinterpret the results of their investigations, alter the conclusion of their work, and at worst, perpetuate false concepts and deceptive hypotheses. Although the routine use of misnomers is more often an annoyance than a critical threat to medical research, this phenomenon can stunt progress and further demonstrates a certain lack of rigor in the scientific process. “Although the routine use of misnomers is more often an annoyance than a critical threat to medical research, this phenomenon can stunt progress and further demonstrates a certain lack of rigor in the scientific process.” In the biological sciences, misnomers can originate from the fact that a gene/protein has two or more possible functions, but that the name in use reflects a minor or even a physiologically irrelevant function of the gene/protein rather than its true role(s). Misnomers also arise because the entity named received its designation based on the first alleged function assigned to it, long before its true function was recognized. A paradigm for these occurrences is the superfamily of nuclear receptors, in which misnomers are widespread. The problems for this group of genes are further compounded in that many nuclear receptors were codiscovered by different groups, each using a different name for the same receptor. In 1999, researchers in the field agreed to a new nomenclature to unambiguously identify each nuclear receptor (2). The nomenclature was based on subfamilies and groups of receptors as part of a phylogenetic tree that connects all known nuclear receptor sequences, and each receptor was assigned an alphanumeric name analogous to a “postal code.” It was recommended that the receptor(s) be identified by the official name(s) at least once in a manuscript, preferably in the abstract and/or the introduction. Once the receptor was matched to its “official name or code,” authors were then encouraged to use the trivial name for the remainder of the manuscript. More on that subject later. Although the use of this nomenclature restored some order in this dysfunctional family, not all authors complied with this mandate, nor did all journals enforce its usage. In addition, curators at the National Center for Biotechnology Information only partially adopted the nomenclature. For example, the official gene name for the estrogen receptor (ER)α is ESR1 (NR3A1 and 5 other names are considered aliases), whereas the official gene name for the orphan nuclear receptor known by its trivial name germ cell nuclear factor (GCNF) is actually NR6A1 (GCNF and 6 other names are considered aliases). In fact, half of the members of the superfamily of nuclear receptors are referred to in GenBank by their trivial names and the other half by the alphanumeric nomenclature. Although the lesser-known retinoic acid receptor-related orphan receptor γ (RORγ) has the official name RORC (not NR3F1 or even RORG like other members with 3 distinct isoforms), the glucocorticoid receptor, universally known as GR, has the official gene name of NR3C1. This is not an inconsequential matter, because investigators outside of the field may not recognize that a nuclear receptor is present in their lists of genes identified as significant in a given functional genomic experiment. This might well result in a missed opportunity to incorporate a nuclear receptor regulatory pathway to a biological process not previously related to endocrine control, thus preventing a critical contribution to endocrine research and to endocrine journals such as Molecular Endocrinology. The universal adoption by National Center for Biotechnology Information of the alphanumeric code instead of a mix of alphanumeric and trivial names for nuclear receptors might have alleviated this issue. Now back to the more important matter of misnomers that designate so many members of the superfamily of nuclear receptors and associated cofactors. Does the name peroxisome proliferator-activated receptor γ (PPARγ) have anything to do anymore with known PPARγ functions? Does the name ER-related receptor α (ERRα) confuse some researchers in thinking that ER-related receptor α is a major contributor to estrogen signaling? Does the name PPARγ coactivator 1 α (PGC-1α) unconsciously link all PPARγ coactivator 1 activity to PPARγ action in the minds of some investigators and thus influence the direction of their research? Although widespread usage of the alphanumeric names would contribute to eliminating this problem, perhaps even more confusion would reign, because these names will no longer relate to the actual function of receptors, especially those with known ligands. For example, the ER (ERα) is the main protein transducing the effect of 17β-estradiol, as is the vitamin D receptor (VDR) for 1,25-dihydroxycholecalciferol. There is no doubt that such deep-rooted names for these receptors and their connection with their actual ligands are more appropriate to designate these proteins. However, even when a specific natural ligand is identified for an orphan receptor, the trivial name often persists in the literature. Such is the case of the mistakenly named farnesoid X receptor (FXR), the actual receptor for bile acids. There is no easy solution to this problem, one that is certainly not unique to the superfamily of nuclear receptors or the broader field of endocrinology but encountered in all fields of biological sciences. The task to arrive at a common framework for a proper nomenclature and its usage is usually decentralized, often left to individual researchers through informal gatherings at scientific meetings. The question is then, should bodies like the Endocrine Society play a more active role in monitoring the use of the scientific nomenclature in their respective fields? Disclosure Summary: The author has nothing to disclose. estrogen receptor retinoic acid receptor-related orphan receptor γ.

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