Heterodimeric Fly Glycoprotein Hormone-α2 (GPA2) and Glycoprotein Hormone-β5 (GPB5) Activate Fly Leucine-Rich Repeat-Containing G Protein-Coupled Receptor-1 (DLGR1) and Stimulation of Human Thyrotropin Receptors by Chimeric Fly GPA2 and Human GPB5

Sudo, Satoko; Kuwabara, Yoshimitsu; Park, Jae-Il; Hsu, Sze-Bi; Hsueh, Aaron J. W.

doi:10.1210/en.2005-0317

Cited by 128 publications

(98 citation statements)

References 28 publications

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“…They may have appeared in the early Cambrian period. Furthermore, in Drosophila melanogaster, a pair of glycoprotein genes, Gpa2 and Gpb5, has been reported and shown to have high homology to mammalian Gpa2 and Gpb5 (32). Fly GPA2 is capable of forming a heterodimer with fly GPB5 to activate a fly receptor, the Drosophila leucine-rich repeat-containing G protein-coupled receptor-1, which shows high homology to mammalian TSHR.…”

Section: Discussionmentioning

confidence: 99%

Thyrostimulin, but Not Thyroid-stimulating Hormone (TSH), Acts as a Paracrine Regulator to Activate the TSH Receptor in Mammalian Ovary

Sun¹,

Hsu²,

Wu³

et al. 2010

Journal of Biological Chemistry

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The thyroid-stimulating hormone receptor (TSHR), activated by either TSH or the newly discovered glycoprotein hormone thyrostimulin, plays a central role in the control of body metabolism. Interestingly, in addition to its thyroid expression, we discovered that the mRNA level of TSHR is periodically regulated in rat ovary by gonadotropins. Ovarian microdissection followed by real-time PCR analysis indicated that granulosa cells show the highest level of TSHR expression. Cultures of follicles and primary granulosa cells demonstrated that the level of TSHR is up-regulated and decreased by the gonadotropindriven cAMP cascade and estradiol production, respectively. Furthermore, in contrast to the negligible expression of TSH in the ovary, we also found by real-time PCR and immunohistochemical analysis that thyrostimulin is expressed mainly in oocytes. Evolving before the appearance of gonadotropins, thyrostimulin is considered the most ancestral glycoprotein hormone. Therefore, the presence of thyrostimulin in the ovary suggests that it may have a primitive function in reproduction when it activates ovarian TSHR. Next, we generated recombinant thyrostimulin protein and characterized its non-covalent heterodimeric nature. Using purified recombinant thyrostimulin, we show that the human ovarian cell line NIH:OVCAR-3 also expresses endogenous and functional TSHR. Using cultured rat granulosa cells isolated from different ovarian stages, we found that treatments with thyrostimulin significantly increase cAMP production and the c-fos gene response in the presence of gonadotropins. Thus, this study demonstrates that oocyte-derived thyrostimulin and granulosa cell-expressed TSHR compose a novel paracrine system in the ovary, where the activity is tightly controlled by gonadotropins.

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Section: Discussionmentioning

confidence: 99%

Thyrostimulin, but Not Thyroid-stimulating Hormone (TSH), Acts as a Paracrine Regulator to Activate the TSH Receptor in Mammalian Ovary

Sun¹,

Hsu²,

Wu³

et al. 2010

Journal of Biological Chemistry

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“…The presence of these receptors suggests that amphioxus also possesses the kisspeptin and GnRH peptides, even though we could not find them in the amphioxus genome; such short sequences are not readily identified by sequence analysis. Amphioxus also has a gene for thyrostimulin, which may be ancestral to three of the pituitary hormones (follicle stimulating hormone, FSH, luteinizing hormone, LH, and thyroid stimulating hormone, TSH) (Sudo et al 2005). However, amphioxus does not appear to have homologs of several vertebrate pituitary hormones [i.e., growth hormone (GH), adrenocorticotropic hormone (ACTH), and prolactin].…”

Section: Pituitary Control Of Reproduction-a Vertebrate Innovationmentioning

confidence: 99%

The amphioxus genome illuminates vertebrate origins and cephalochordate biology

Holland¹,

Albalat²,

Azumi³

et al. 2008

Genome Res.

462

402

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Cephalochordates, urochordates, and vertebrates evolved from a common ancestor over 520 million years ago. To improve our understanding of chordate evolution and the origin of vertebrates, we intensively searched for particular genes, gene families, and conserved noncoding elements in the sequenced genome of the cephalochordate Branchiostoma floridae, commonly called amphioxus or lancelets. Special attention was given to homeobox genes, opsin genes, genes involved in neural crest development, nuclear receptor genes, genes encoding components of the endocrine and immune systems, and conserved cis-regulatory enhancers. The amphioxus genome contains a basic set of chordate genes involved in development and cell signaling, including a fifteenth Hox gene. This set includes many genes that were co-opted in vertebrates for new roles in neural crest development and adaptive immunity. However, where amphioxus has a single gene, vertebrates often have two, three, or four paralogs derived from two whole-genome duplication events. In addition, several transcriptional enhancers are conserved between amphioxus and vertebrates-a very wide phylogenetic distance. In contrast, urochordate genomes have lost many genes, including a diversity of homeobox families and genes involved in steroid hormone function. The amphioxus genome also exhibits derived features, including duplications of opsins and genes proposed to function in innate immunity and endocrine systems. Our results indicate that the amphioxus genome is elemental to an understanding of the biology and evolution of nonchordate deuterostomes, invertebrate chordates, and vertebrates.

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“…With the discovery of GPA2 and glycoprotein-β subunit 5 (GPB5, thyrostimulin-β) homologs not only in other vertebrates but invertebrates-including fly, nematode, and sea urchin (14, 15)-it is proposed that an ancestral glycoprotein (GP) existed before the divergence of vertebrates and invertebrates, and that later geneduplication events in vertebrates produced the thyrostimulin (GPA2 and GPB5) and GTH/TSH [GPHα and GPHβ (LHβ/ FSHβ/TSHβ)] (Fig. S1) (14). The basal lineage of chordates, such as tunicates and amphioxus, contains GPA2 and GPA5 in their genome but not GPHα and GPHβ (16)(17)(18)(19).…”

mentioning

confidence: 99%

Evolutionary origin of a functional gonadotropin in the pituitary of the most primitive vertebrate, hagfish

Uchida

Moriyama

Chiba

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Hagfish, which lack both jaws and vertebrae, are considered the most primitive vertebrate known, living or extinct. Hagfish have long been the enigma of vertebrate evolution not only because of their evolutionary position, but also because of our lack of knowledge on fundamental processes. Key elements of the reproductive endocrine system in hagfish have yet to be elucidated. Here, the presence and identity of a functional glycoprotein hormone (GPH) have been elucidated from the brown hagfish Paramyxine atami. The hagfish GPH consists of two subunits, α and β, which are synthesized and colocalized in the same cells of the adenohypophysis. The cellular and transcriptional activities of hagfish GPHα and -β were significantly correlated with the developmental stages of the gonad. The purified native GPH induced the release of gonadal sex steroids in vitro. From our phylogenetic analysis, we propose that ancestral glycoprotein α-subunit 2 (GPA2) and β-subunit 5 (GPB5) gave rise to GPHα and GPHβ of the vertebrate glycoprotein hormone family, respectively. The identified hagfish GPHα and -β subunits appear to be the typical gnathostome GPHα and -β subunits based on the sequence and phylogenetic analyses. We hypothesize that the identity of a single functional GPH of the hagfish, hagfish GTH, provides critical evidence for the existence of a pituitary-gonadal system in the earliest divergent vertebrate that likely evolved from an ancestral, prevertebrate exclusively neuroendocrine mechanism by gradual emergence of a previously undescribed control level, the pituitary, which is not found in the Protochordates.

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Heterodimeric Fly Glycoprotein Hormone-α2 (GPA2) and Glycoprotein Hormone-β5 (GPB5) Activate Fly Leucine-Rich Repeat-Containing G Protein-Coupled Receptor-1 (DLGR1) and Stimulation of Human Thyrotropin Receptors by Chimeric Fly GPA2 and Human GPB5

Cited by 128 publications

References 28 publications

Thyrostimulin, but Not Thyroid-stimulating Hormone (TSH), Acts as a Paracrine Regulator to Activate the TSH Receptor in Mammalian Ovary

Thyrostimulin, but Not Thyroid-stimulating Hormone (TSH), Acts as a Paracrine Regulator to Activate the TSH Receptor in Mammalian Ovary

The amphioxus genome illuminates vertebrate origins and cephalochordate biology

Evolutionary origin of a functional gonadotropin in the pituitary of the most primitive vertebrate, hagfish

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