Front-loading and the Endocrine System

Human insulin has the ability to mimic a growth factor for the single celled organism, Tetrahymena. But did you know that Tetrahymena’s ability to respond to mammalian insulin has been extensively studied?

For example, Tetrahymena produce an insulin-like molecule that is detectable with an antibody that specifically binds human insulin. It turns out that when Tetrahymena cells are starved, they increase the expression of this insulin. [1] In fact, you can stimulate Tetrahymena to uptake glucose by adding mammalian insulin to the culture, [2] the very type of response we see in mammalian cells. Mammalian insulin has also been shown to stimulate an adenyl cyclase signaling system in Tetrahymena, [3] a circuit that has also been studied mammalian cells [4]. The discovery of an insulin-activated adenyl cyclase in Tetrahymena led the researchers to conclude that “at the earliest stages of evolutionary development of unicellular organisms the molecular mechanisms providing hormonal regulation of various cellular processes have already been formed in these organisms.” Echoes of front-loading?

But it gets better. Not only does this protozoan possess insulin-receptors, insulin-like molecules, and respond to mammalian insulin, but it turns out that Tetrahymena respond to mammalian hormones and possess many mammalian-like hormones:

Phagocytosis in Tetrahymena is enhanced by histamine and serotonin but no reaction has been observed to the chemically related indoleacetic acid, insulin influences its sugar uptake and triiodothyronine enhances its cell division. Tetrahymena also contains (produces, stores and secretes) vertebrate-hormone-like molecules, such as insulin, relaxin, adrenocorticotrophic hormone, endothelin, serotonin and histamine. The first encounter that Tetrahymena makes with a hormone provokes hormonal imprinting, following which the capacity of its binding sites and its hormone content change for hundreds of generations. A signal transduction system, similar to the mammalian system, is also present in Tetrahymena. Thus, the unicellular Tetrahymena has each component of an endocrine system. (emphasis added). [5]

Given that the endocrine system (our system of glands and hormones) plays an essential role in animal life, that a single-celled organism can possess “each component of an endocrine system” clearly adds to the growing plausibility of front-loading, as the core functional elements of this system can be packaged in a unicellular lifestyle. This point is further emphasized by the fact that human or bovine insulin can influence cell behavior in Hydra, plants, and even protozoa.

1. Csaba G, Kovács P, Pállinger E. 2007. Effect of starvation on insulin production and insulin binding in Tetrahymena. Cell Biochem Funct. 25:473-7.

2. Csaba G, Lantos T. 1975. Effect of insulin on the glucose uptake of protozoa. Experientia. 31:1097-8.

3. Shpakov AO, Derkach KV, Uspenskaia ZI, Shpakova EA, Kuznetsova LA, Plesneva SA, Pertseva MN. 2004. Regulation of Adenylyl Cyclase Signaling System in Cell Cultures of Infusoria Dileptus anser and Tetrahymena pyriformis by Peptides of Insulin Superfamily Journal of Evolutionary Biochemistry and Physiology 40: 364-373.

4. Pertseva MN, Plesneva SA, Shpakov AO, Rusakov YuI , Kuznetsova LA. 1995. Involvement of the adenylyl cyclase signaling system in the action of insulin and mollusk insulin-like peptide. Comp Biochem Physiol B Biochem 112:689-95.

5. G. Csaba . P. Kovács . Éva Pállinger. 2005. How does the unicellular Tetrahymena utilise the hormones that it produces? Paying a visit to the realm of atto-and zeptomolar concentrations. Cell Tissue Res 327: 199–203.


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