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General Comment |
Hsu et al 2002 reported the evolution of glycoprotein hormone subunit genes in bilateral metazoa: identification of two novel human glycoprotein hormone subunit family genes, GPA2 and GPB5.
The canonical members of the human glycoprotein hormone subunit family of cystine knot-forming polypeptides include the common alpha-subunit, and four beta-subunit genes, FSHbeta, LHbeta, TSHbeta, and hCGbeta. Using pairwise sequence analysis of the complete human genome, we have identified two novel glycoprotein hormone subunit-related genes. Based on unique sequence similarity to the alpha- and beta-subunits of glycoprotein hormones, they were named glycoprotein-alpha2 (GPA2) and glycoprotein-beta5 (GPB5), respectively. PCR analysis using a panel of human cDNAs from 14 different tissues demonstrated that GPB5 is similar to other beta-subunits showing restricted tissue expression, mainly in pituitary and brain. In contrast, the GPA2 transcript is found in diverse tissues. Furthermore, immunoreactive GPA2 and GPB5 were detected in the anterior pituitary of mouse and frog, whereas the expression of GPA2 and GPB5 in transfected cells resulted in the secretion of recombinant polypeptides in conditioned medium. After GenBank searches in lower organisms, glycoprotein hormone beta-subunit-related genes were identified from the genome of nematode Caenorhabditis elegans, hookworm Ancylostoma caninum, and Drosophila melanogaster. The evolutionary conservation of these invertebrate homologs can be seen in several key sequence characteristics, and the data suggest that the glycoprotein hormone beta-subunit gene ancestor evolved before the emergence of bilateral metazoa, thus providing a better understanding of the evolution of this group of classic polypeptide hormones and their receptors. Studies of the complete inventory of genes homologous to glycoprotein hormone subunits in the human genome and lower organisms will allow future functional characterization and identification of their respective receptors.
GPA@ was found in the ovary based on RT-PCR.
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Comment |
Neuroendocrine cells in Drosophila melanogaster producing GPA2/GPB5, a hormone with homology to LH, FSH and TSH. Sellami A et al. Thyrostimulin is a dimer hormone formed from glycoprotein A2 (GPA2) and glycoprotein B5 (GPB5) that activates the TSH receptor in vertebrates. A Drosophila GPA2/GPB5 homolog has recently been characterized. Cells producing this novel hormone were localized by in situ hybridization using both the GPA2 and GPB5 DNA sequences and by making transgenic flies in which the GPB5 promoter drives the expression of gal4. Endocrine cells producing GPA2/GPB5 were found in the abdominal neuromeres and are different from the endocrine cells producing crustacean cardioactive peptide or those making leucokinin. They are also not immunoreactive to antisera to the CRF- or calcitonin-like diuretic hormones. Their axons leave the central nervous system through the segmental nerves and project to the periphery were they likely release GPA2/GPB5 into the hemolymph. As has been described for the leucokinin endocrine cells their axons run over the surface of the abdominal musculature, however the projection patterns of the leucokinin and GPA2/GPB5 neuroendocrine cells are not identical. The chances of adult eclosion of insects from which the GPA2/GPB5 cells have been genetically ablated or have been made to express GPB5-RNAi are severely compromised, demonstrating the physiological importance of the cells producing this hormone. As the receptor for GPA2/GPB5 stimulates the production of cyclic AMP (cAMP) and is highly expressed in the hindgut, where cAMP stimulates water reabsorption in locusts, it is suggested that GPA2/GPB5 may be an insect antidiuretic hormone.
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