Endocrine archeology: Do insects retain ancestrally inherited counterparts of the vertebrate releasing hormones GnRH, GHRH, TRH, and CRF?

Vertebrate releasing hormones include gonadotropin releasing hormone (GnRH), growth hormone releasing hormone (GHRH), corticotropin releasing hormone (CRF), and thyrotropin-releasing hormone (TRH). They are synthesized in the hypothalamus and stimulate the release of pituitary hormones. Here we review the knowledge on hormone releasing systems in the protostomian lineage. We address the question: do insects have peptides that may be phylogenetically related to an ancestral GnRH, GHRH, TRH, and CRF? Such endocrine archeology has become possible thanks to the growing list of fully sequenced genomes as well as to the continuously improving bioinformatic tool set. It has recently been shown that the ecdysozoan (nematodes and arthropods) adipokinetic hormones (AKHs), the lophotrochozoan (annelids and mollusks) GnRHs as well as the protochordate GnRHs are structurally related. The adipokinetic hormone precursor-related peptides (APRPs), in locusts encoded by the same gene that contains the AKH-coding region, have been forwarded as the structural counterpart of GHRH of vertebrates. CRF is relatively well conserved in insects, in which it functions as a diuretic hormone. Members of TRH-receptor family seem to have been conserved in some arthropods, but other elements of the thyroid hormone signaling system are not. A challenging idea is that in insects the functions of the thyroid hormones were taken over by juvenile hormone (JH). Our reconstruction suggests that, perhaps, the ancestral releasing hormone precursors played a role in controlling energy metabolism and water balance, and that releasing hormone functions as present in extant vertebrates were probably secondarily acquired.

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► A nematodes peptide activates both the GnRH and the insect adipokinetic hormone (AKH) receptor.
► The very ancient ancestor of growth hormone releasing hormone (GHRH) may have been glucagon-like.
► A challenging hypothesis: juvenile hormone developed as ersatz for thyroid hormone signaling.
► CRF is well conserved in insects and functions as an antidiuretic hormone.
► The ancestral releasing hormone precursors may have controlled energy and water metabolism.