Abstract

The unicellular Tetrahymena distinguishes structure-related vertebrate hormones by its chemosensory reactions. In the present work, the selectivity of hormone receptors was evaluated by analyzing the effects of various gonadotropin-releasing hormone (GnRH) analogs (GnRH-I, GnRH-III) as well as truncated (Ac-SHDWKPG-NH2) and dimer derivatives ([GnRH-III(C)]2 and [GnRH-III(CGFLG)]2) of GnRH-III on (i) locomotory behaviors, (ii) cell proliferation, and (iii) intracellular hormone contents of Tetrahymena pyriformis. The migration, intracellular hormone content, and proliferation of Tetrahymena were investigated by microscope-assisted tracking analysis, flow cytometry, and a CASY TT cell counter, respectively. Depending on the length of linker sequence between the two GnRH-III monomers, the GnRH-III dimers had the opposite effect on Tetrahymena migration. [GnRH-III(CGFLG)]2 dimer had a slow, serpentine-like movement, while [GnRH-III(C)]2 dimer had a rather linear swimming pattern. All GnRH-III derivatives significantly induced cell growth after 6 h incubation. Endogenous histamine content was uniformly enhanced by Ac-SHDWKPG-NH2 and GnRH-III dimers, while some differences between the hormonal activities of GnRHs were manifested in their effects on intracellular levels of serotonin and endorphin. The GnRH peptides could directly affect Tetrahymena migration and proliferation in a structure-dependent manner, and they could indirectly regulate these reactions by paracrine/autocrine mechanisms. Present results support the theory that recognition ability and selectivity of mammalian hormone receptors can be deduced from a phylogenetically ancient level like the unicellular Tetrahymena.

Highlights

  • In the early seventies of the last century, the presence of receptors for hormones of higher vertebrates has been demonstrated in the unicellular Tetrahymena [1,2,3]

  • Our experiment clearly showed that gonadotropin-releasing hormone (GnRH) peptides can influence many essential cell physiological processes of Tetrahymena

  • The structural modifications of GnRH peptides resulted in different migratory activities as well as changes in cell proliferation and the levels of intracellular hormones

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Summary

Introduction

In the early seventies of the last century, the presence of receptors for hormones (e.g., insulin receptor) of higher vertebrates has been demonstrated in the unicellular Tetrahymena [1,2,3]. The similarities of the receptors, hormones, and signal pathways to the vertebrate ones were demonstrated [3,5,11]. The recognition of hormones of the higher-ranked animal proved to influence (i) the chemosensory behavior of Tetrahymena, such as chemotaxis [12] and chemokinesis [13], (ii) cell survival and proliferation [14], as well as (iii) production and secretion of hormones, which imply paracrine/autocrine communication [3]. Former data about the highly sensitive chemotactic responsiveness of Tetrahymena to peptide-type hormones and their structure-related derivatives (e.g., bradykinin and its truncated fragments [17]; oxytocin and its synthetic analogues [18]) point to the selectivity of these hormone receptors

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