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The facts of the matter: What is a hormone?

G. Karsenty

Published 2020 in PLoS Genetics

ABSTRACT

By choice, scientists value facts over beliefs. This is why science is constantly moving forward; it embraces novelty, provided it is fortified by evidence and all sorts of controls, checks and balances, as a sign of and a tool for progress. A goal common to all individuals that devote their life to science is to advance knowledge. They may have other goals but this particular one has to be common to all scientists. This goal also creates a burden and not such an easy one to bear—the burden of restraint. Scientists live under the public light: they publish, i.e., share their findings with the scientific community at large and sometimes with the general public. What comes with that are huge responsibilities, the one to be right of course, but more importantly the responsibility to be cautious, to stay within the data and to not drag them beyond what they actually show. Otherwise the pursuit of knowledge is, unwillingly but definitely, tainted. Results have to be controlled over and over, and of course, just as importantly, their presentation has to be neutral as opposed to clever. This serves as a necessary preamble to a series of facts. The word hormone means “that which sets in motion”, and was first used in 1902 before the emergence of molecular biology, yet its carefully worded definition has essentially remained unchanged. This definition is at the heart of this piece and our work on the endocrinology of bone over the past 13 years. To be clear, a hormone is defined both experimentally and physiologically by what it does when present in abundance in animals or in humans because of an environmental stimulus, physiological perturbation, tumor, genetic abnormality, or when injected in an otherwise normal human being or animal of any species. As long as a molecule has not been shown to affect a particular physiological function when injected in a normal animal, it may be many things, it may have many names but a hormone it may not be. I cite here a recent and vivid example of what I write. Mice lacking the GLP1 receptor have a mild metabolic phenotype at best, yet GLP1 plays a critical role in physiology and its analogs are best-selling drugs for the treatment of diabetes [1]. Likewise, the blossoming field of FGF21 biology is based on gain of function experiments. What I write is not meant to disparage mouse genetics since it is part of what my lab has used to address many questions in the field of bone biology and I have learnt to appreciate its value. It is rather meant to remind myself and everyone else that biology is an assembly of disciplines and approaches. Scientists are not and should not be children in a toy store. The newest tool does not, and is not meant to, replace the older one, rather it enriches the tool kit. Even more to the point, one experimental approach with very small N, based on erroneous protocols, using mixed genetic backgrounds, does not suffice to invalidate, even if carefully worded, the work done by many others using multiple and state-of-the-art experimental approaches. I write the preceding to introduce another fact: osteocalcin was shown to have properties of a hormone in mice, rats, monkeys and subsequently humans through gain-of-function experiments [2–52]. Those experiments occupy more than half of the original paper [50]. It was the PLOS GENETICS

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