Amphioxus Hormones

Cross references:   Hormones in General     Endostyle = Thyroid   
Amphioxus Gut Hormones   Lamellar Body = Pineal Gland Amphioxus Pituitary      
Amphioxus Gonads    Amphioxus Stress Hormones  
Amphioxus Oxytocin    Amphioxus Insulin    Insulin-like Growth Factor  
 Amphioxus Genomics     Amphioxus Receptors     Amphioxus Neurotransmitters    
Lamprey Hormones Shark Hormones Teleost Hormones Evolution of Hormones
Human Endocrinology in General  CYP450 Enzymes 

Searching Google for "amphioxus hormones" yielded 35,700 references:          

Searching PubMed for "amphioxus hormones" originally yielded 72 references.  This later expanded to 73:         

1960    72<72   
[On the formation of thyroid hormones and of their precursors by Branchiostoma lanceolatum Pallas (Amphioxus)].    (French)   
    No Abstract but 90 Similar articles:  
      See:  Endostyle = Thyroid

1962    71<72      
Identification of labeled thyroxine and triiodothyronine in amphioxus treated with 131-I.   
    No Abstract, but 163 Similar articles.    
    See:  Endostyle = Thyroid .   

70<72    N/A 

1984    69<72  38<38 
In vitro conversion of androgen to estrogen in amphioxus gonadal tissues.      
    See:  Amphioxus Gonads

1990     68<72 
Evolution of the insulin superfamily: cloning of a hybrid insulin/insulin-like growth factor cDNA from amphioxus.   
    See:   Amphioxus Insulin
    "Although insulin and the insulin-like growth factors (IGFs) share marked similarities in amino acid sequence and biological activity, their evolutionary origins have not been resolved. To investigate this issue, we recently cloned a cDNA encoding an insulin-like peptide (ILP) from a primitive chordate species, amphioxus (Branchiostoma californiensis). The deduced sequence of amphioxus preproILP indicates that it is a hybrid molecule containing features characteristic of both insulin and IGF. Like proinsulin, amphioxus proILP contains a C-peptide, which is flanked by paired basic residues and is probably removed by proteolysis. However, proILP also contains an extended carboxyl-terminal peptide region that can be divided into D and E domains similar to those of proIGF. Sequence comparisons show that the amphioxus ILP A and B domains are equally homologous to those of human insulin and IGF-I and -II. Based on these results and the exon-intron organization of the amphioxus ILP gene, we propose that IGF emerged at a very early stage in vertebrate evolution from an ancestral insulin-type gene."   
    - Free PMC Article -   

1991    67<72 
Correlation of annual change of luteinizing hormone-releasing hormone (LH-RH) with gonadal development in amphioxus.   
    See:   Amphioxus Gonads

1994    66<72    
Gene duplications and the origins of vertebrate development. - PubMed   
    See:  Genomics in General

1994    66<73 
Hormonal regulation of oocyte development and maturation of amphioxus.   
See:   Amphioxus Gonads

1994    65<73  
 Insulin-like compounds related to the amphioxus insulin-like peptide.

    See:  Amphioxus Insulin    .

63.  N/A 

62.  N/A 
1997    61<72 
Ancient divergence of insulin and insulin-like growth factor.   
   See:  Amphioxus Insulin    . 

1998    60<72 
Localization and partial characterization of melatonin receptors in amphioxus, hagfish, lamprey, and skate.
      See:   Lamellar Body = Pineal Gland .  

1999    59<72 
A brain-Hatschek's pit connection in amphioxus (PubMed)   
    "In the adult lancelet, Branchiostoma belcheri, there is a lobe of the right ventral margin of the brain that extends around the right side of the notochord and makes contact with Hatschek's pit, which also is to the right of the midline. This structural system resembles the hypothalamo-adenohypophyseal system of vertebrates and appears to make possible seasonal nervous regulation of the release of gonadotropin." 
    See also:  Amphioxus Pituitary and  Amphioxus Asymmetry   . 

1999    58<72 
[Distribution of luteinizing hormone (LH) and human chorionic gonadotropin (hCG) in the nervous system, Hatschek's pit and gonads of protochordata].   
    See:   Amphioxus Gonads

2002    57<72 
  In vitro evolution of amphioxus insulin-like peptide to mammalian insulin.
    See:  Amphioxus Insulin    . 

2002    56<72   
[Distribution of neuropeptide Y-like and beta-endorphin-like immunoreactivity in the nervous system and Hatschek's pit of amphioxus, Branchiostoma ...     (Chinese)   
    See:   Amphioxus Pituitary

2003    55<72 
Evolution of adrenal and sex steroid action in vertebrates: a ligand-based mechanism for complexity.   
    See:  Amphioxus Gonads

2003     55<73 
Immunoreactivity for progesterone in the giant Rohde cells of the amphioxus, Branchiostoma belcheri. 
   "In higher animals, it is now generally accepted that neurosteroids are steroids that are synthesized in the brain itself, but it remains unclear where, in terms of the phylogeny of chordates, such neurosteroids are first synthesized?  
    We have tried to detect progesterone immunohistochemically in the central nervous system of the amphioxus, Branchiostoma belcheri, an ancient species of chordate. We found immunoreactivity specific for progesterone in the giant neurons known as Rohde cells, at sites that included the perikaryon, in axons and in a thick coarse axon in addition to the gonads.  
    Thus, the present progesterone-like substance appeared to be a phylogenetically ancient and ancestral neurosteroid. Rohde cells are known to be the source of Mauthner cells and to act as interneurons and, therefore, it seems possible that progesterone-like substance might be involved in primitive sigmoid movement, acting as a chemical signal. The presence of progesterone-like substance in amphioxus suggests that animals have evolved by effectively exploiting a rather limited number of active compounds. This report is the first, to our knowledge, to demonstrate that the Rohde cells in the spinal cord of amphioxus have progesterone-like substance, which might be involved in swimming."   

Refolding of amphioxus insulin-like peptide: implications of a bifurcating evolution of the different folding behavior of insulin and insulin-like growth factor 1.    

Co-evolution of steroidogenic and steroid-inactivating enzymes and adrenal and sex steroid receptors.  

Phylogenetic analysis and developmental expression of thymosin-beta4 gene in amphioxus.

    See:  Endostyle = Thyroid .   

Presence of sex steroids and cytochrome P450 genes in amphioxus.

2007      47<73 
Amphioxus, a Primitive Chordate, Is on Steroids: Evidence for Sex Steroids  (Goog).
This full length article is available online, however it was written before the amphioxus geneome had been fully sequenced.  It's value lies in the historical background it provides. 
    "In the 1950s, Jensen’s laboratory began investigating the mechanism of action of estradiol, which lead to the identification of the estrogen receptor (ER) as a mediator of estrogen action (1). The 1970s witnessed the characterization of the other adrenal and sex steroid receptors: the progesterone receptor (PR) ( 2), the glucocorticoid receptor (GR) ( 3), the mineralocorticoid receptor (MR) ( 4), and the androgen receptor (AR) ( 5).   
    An important next step, determining the sequences of these steroid receptors, came more slowly because it was difficult to get sufficient purified protein for sequencing. This obstacle was resolved in the mid-1980s, when molecular techniques led to the cloning of the genes for adrenal and sex steroid receptors ( 2, 6, 7), which permitted an evolutionary analysis of their relationships with each other.  
    Unexpectedly, steroid receptors were found to be related to the thyroid hormone receptor, retinoic acid receptor, and vitamin D receptor, all of which are now classified as belonging to the nuclear receptor family of transcription factors ( 8, 9, 10). Sequence analyses placed adrenal and sex steroid receptors on a branch separate from other nuclear receptors ( 9, 10, 11, 12). The AR, PR, GR, and MR cluster together, with the ER on a separate branch.  
    In the 1990s, further advances in cloning technology ushered in a Golden Age for evolutionary biology. It became possible to think about cloning entire genomes of bacteria, unicellular eukaryotes, and even multicellular animals and plants, which it was hoped would yield important medical and agricultural benefits, as well as providing information for understanding the evolution of life on earth. With an inventory of genes from bacteria, yeast, plants, flies, fish, amphibians, and mammals, among others, it might be possible to understand the transition from prokaryotes to eukaryotes, the origins of plants, multicellular animals, and vertebrates and the evolution of various signaling pathways, including that of steroids. Indeed, as gene sequences from diverse organisms became available, and newspapers increasingly contained articles on evolution, such as the relationship of humans to other primates, and the origins of eyes, Dobzhansky’s statement in 1973 that "Nothing in biology makes sense except in the light of evolution" ( 13) captured the imagination of biologists and the public at large.  
    As various genomes were sequenced, there were surprises. Steroid receptors and other nuclear receptors were not found in either yeast or plants, despite evidence that the ER ( 14) and GR ( 15) could function in yeast, and the GR could function in plants ( 16). These studies indicated that the transcriptional machinery for responding to nuclear receptors is present in yeast and plants, but nuclear receptors evolved later in multicellular animals.  
    Another surprise was the absence of adrenal and sex steroid receptors in the fruit fly and roundworm, although both invertebrates have nuclear receptors. And, although distant ancestors of the ER have been found in octopus, snails, and other mollusks, these ERs are active in the absence of steroids and do not bind estradiol or other steroids ( 17, 18, 19, 20). 
    When did adrenal and sex steroids begin to regulate gene transcription in animals ( 11, 21)? Steroid receptors are found in vertebrates, including lamprey and hagfish ( 22, 23), which are jawless fish at the base of the vertebrate line (Fig. 1). Is this when adrenal and sex steroids first began to regulate gene transcription, or was it earlier? Recently, the sea urchin genome, a basal deuterostome (Fig. 1), was sequenced and found to contain 33 nuclear receptors ( 24). None, however, were orthologs of a steroid receptor.    
    A good candidate to contain a steroid receptor is amphioxus (Branchiostoma), which is a member of the chordate phylum and phylogenetically close to lamprey and hagfish (Fig. 1). Amphioxus has a similar body plan as vertebrates, with the experimental advantage of a simpler anatomy and physiology than vertebrates. As a result, amphioxus is an important model organism for studying the evolution of development in vertebrates ( 25, 26), which led to selection of the amphioxus genome for sequencing.  When the amphioxus genome is sequenced, it should answer many questions about when proteins involved in steroid hormone action evolved." 
    "In summary, Mizuta and Kubakawa provide strong evidence that the enzyme pathway for the synthesis of three steroids with reproductive activity in vertebrates is present in amphioxus. This contrasts with the tunicate, Ciona intestinalis, another protochordate that is close to vertebrates (Fig. 1), which lacks steroid receptors and CYP450s for steroid synthesis ( 30).  
    Thus, amphioxus is the most ancient animal that is known to have CYP450 enzymes for synthesis of vertebrate sex steroids." 
   "Abbreviations: AR, Androgen receptor; DHEA, dehydroepiandrosterone; ER, estrogen receptor; GR, glucocorticoid receptor; 3?-HSD, 3?-hydroxysteroid dehydrogenase; MR, mineralocorticoid receptor; PR, progesterone receptor."   

Figure 1 of Figure

Fig. 1. Amphioxus in an evolutionary context. Amphioxus and Ciona are close relatives to vertebrates. Hagfish and lamprey contain steroid receptors; and Ciona and sea urchin do not contain steroid receptors.  

My comment:     
    I was surprised. Although the HOX genes are present in the fruit fly, amphioxus and humans, the endocrine system is not as broadly universal. As of 2007, there are indications that the sex steriods are present and active in amphioxus, this was not unequivocally determined. However, the estrogen receptor, the progesterone receptor (PR), the glucocorticoid receptor (GR), the mineralocorticoid receptor (MR), and the androgen receptor (AR) were all identified and sequenced.  

46<73    Free PMC Article   
N-methyl-D-aspartic acid (NMDA) in the nervous system of the amphioxus Branchiostoma lanceolatum.   

43<73       Free Article   
Amphioxus postembryonic development reveals the homology of chordate metamorphosis.

42<73       Free Article
Chordate metamorphosis: ancient control by iodothyronines.   
    See:  Endostyle = Thyroid .

Motif analysis of amphioxus, lamprey and invertebrate estrogen receptors: toward a better understanding of estrogen receptor evolution.

40<73       Free PMC Article   
An amphioxus orthologue of the estrogen receptor that does not bind estradiol: insights into estrogen receptor evolution. 

The history of a developmental stage: metamorphosis in chordates.

The amphioxus genome illuminates vertebrate origins and cephalochordate biology  
Full length HTML available online for free.  
     "The primary vertebrate endocrine organs (pineal gland, ovary, testis, endostyle/thyroid, brain, gut, and pituitary) have structurally simpler homologs in amphioxus." 
    For more from this paper, see: Amphioxus Genomics  ,  Amphioxus Hormones
Endostyle = Thyroid , Amphioxus Gut Hormones  .   

2008     38<73 
Nuclear hormone receptor signaling in amphioxus.  
    "The nuclear hormone receptors (NRs) form a superfamily of transcription factors unified by conserved protein structure and mode of function. While most members of this superfamily are activated by ligands, such as thyroid hormones, steroids, vitamin D or retinoic acid, other NRs are called orphan receptors because they have no known ligand.  
    NR-dependent signaling is crucial for vertebrate development with the majority of receptors being expressed in the developing embryo. Due to massive gene duplications during vertebrate diversification, there are usually more NRs in vertebrates than in invertebrates. In this study, we examine the evolutionary diversification of the NR superfamily and of NR-dependent signaling in chordates (vertebrates, tunicates, and amphioxus). We take advantage of the unique features of the genome of the invertebrate amphioxus, which is characterized by a vertebrate-like gene content without having undergone massive duplications, to assess the NR signaling complement (NRs and NR coregulators) of the ancestral chordate.  
    We find 33 NRs in amphioxus, which are more NRs than originally anticipated. This increase is mainly due to an amphioxus-specific duplication of genes encoding receptors of the NR1H group. In addition, there are three heterologous NRs in amphioxus that could not be placed within the framework of the NR superfamily. Apart from these exceptions, there is usually one amphioxus NR or NR signaling coregulator for each paralogous group of two, three, or four human receptors suggesting that the ancestral chordate had a set of 22 different NRs plus one copy of each NR coregulator."  

The amphioxus genome enlightens the evolution of the thyroid hormone signaling pathway. 

2009   35<72 
Characterization and putative role of a type I gonadotropin-releasing hormone in the cephalochordate amphioxus.  
    "Employing reverse-phase chromatography, we purified a peptide of relative molecular mass of 1182.60 Da from the cephalochordate amphioxus Branchiostoma lanceolatum. We found that its amino acid sequence (pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH(2)) was identical to that of mammalian GnRH."    
    See:  Amphioxus Pituitary

2009    35<73   
Free PMC Article   
Characterization of the neurohypophysial hormone gene loci in elephant shark and the Japanese lamprey: origin of the vertebrate neurohypophysial hormone genes.

2009    33<72     
A homolog of the vertebrate thyrostimulin glycoprotein hormone alpha subunit (GPA2) is expressed in Amphioxus neurons.   
      See:  Endostyle = Thyroid

2009    33<73  

Expression of the gene for ancestral glycoprotein hormone beta subunit in the nerve cord of amphioxus.

2009    32<73
Distinct expression patterns of glycoprotein hormone-alpha2 and -beta5 in a basal chordate suggest independent developmental functions.  
      See:  Endostyle = Thyroid

2009    30<72  
3D model of amphioxus steroid receptor complexed with estradiol.   
    See:   Estrogen Receptor

2009    29<72  
Up-regulation of C/EBP by thyroid hormones: a case demonstrating the vertebrate-like thyroid hormone signaling pathway in amphioxus.   
      See:  Endostyle = Thyroid

2010    28<72 
Estrogen-dependent transactivation of amphioxus steroid hormone receptor via both estrogen and androgen response elements.   
    See:  Estrogen Receptor

2010    28<73      
[Hepatic caecum of amphioxus and origin of vertebrate liver].

2010    27<73   
Free Article   
Evolution of 11beta-hydroxysteroid dehydrogenase-type 1 and 11beta-hydroxysteroid dehydrogenase-type 3.

2010    25<72   
"Insights of early chordate genomics: endocrinology and development in amphioxus, tunicates and lampreys": introduction to the symposium.  
    Full-length text:  
    See:  Amphioxus Genomics  . 

2010      24<72     
Evolution of the Reproductive Endocrine System in Chordates (Goog)   
    Full length HTML & PDF available online for free. 
Click on the appropriate link.     

    See:   Amphioxus Gonads .

2010   23<72 
Active metabolism of thyroid hormone during metamorphosis of amphioxus.  
    See:  Endostyle = Thyroid

2010    23<73   
Free Article   
Genomics reveal ancient forms of stanniocalcin in amphioxus and tunicate.

2011    21<72  
Evolution of the gonadotropin-releasing hormone (GnRH) gene family in relation to vertebrate tetraploidizations.   
    See:   Amphioxus Gonads .

2011  20<72 
Nuclear hormone receptors in chordates.  
    See:  Intracellular Receptors

2011    19<72 
A nonselenoprotein from amphioxus deiodinates triac but not T3: is triac the primordial bioactive thyroid hormone?   
    See:  Endostyle = Thyroid

2011 18<72
Evolutionary origins of the estrogen signaling system: insights from amphioxus. 
    Full length paper:    
    See:   Estrogen  . 

2011    18<73   
Emergence and evolution of the glycoprotein hormone and neurotrophin gene families in vertebrates.   
    See:  Amphioxus Pituitary

2011    16<72 
Expression and regulation by thyroid hormone (TH) of zebrafish IGF-I gene and amphioxus IGFl gene with implication of the origin of TH/IGF signaling pathway.  
    See:  Endostyle = Thyroid .

2013   15<72
Thyroid hormones and postembryonic development in amniotes.  
    See:  Endostyle = Thyroid .

2012    15<73       
Identification and bioactivity analysis of transthyretin-like protein in amphioxus: a case demonstrating divergent evolution from an enzyme to a hormone.   
    See:  Endostyle = Thyroid .  

2013    14<73 
Structural and functional analysis of the amphioxus IGFBP gene uncovers ancient origin of IGF-independent functions.   
    See:  Hormones in General  . 

2013    13<73   
Free PMC Article    
Drastic neofunctionalization associated with evolution of the timezyme AANAT 500 Mya.

2014    12<73 
At the transition from invertebrates to vertebrates, a novel GnRH-like peptide emerges in amphioxus.   
    See:  Gonadotropin-Releasing Hormone (GnRH)   . 

2014    11<73 
Characterization of insulin-like peptides (ILPs) in the sea urchin Strongylocentrotus purpuratus: insights on the evolution of the insulin family.   
    See:  Hormones in General

2014    10<73 
GnRH receptors and peptides: skating backward.   
    See:  Gonadotropin-Releasing Hormone (GnRH)   . 

2014    9<73 
Growth hormone -  Functional characterization of GH-like homolog in amphioxus reveals an ancient origin of GH/GH receptor system.  
    See: Hormones in General for 2 full length references. 

2015    8<73 
Identification, evolution and expression of an insulin-like peptide in the cephalochordate Branchiostoma lanceolatum.   
    See:  Amphioxus Insulin   and   Free PMC Article    . 

2015    7<73     Free PMC Article   

Evolution of the Role of RA and FGF Signals in the Control of Somitogenesis in Chordates.    

2015    6<73 
Dehydroepiandrosterone: an ancestral ligand of neurotrophin receptors.  
    See:  Hormones in General .

2015    5<73 
An evolutionary scenario for gonadotrophin-inhibitory hormone in chordates.   
    See:  Gonadotropin-Releasing Hormone (GnRH)   . 

2014    4<73 
Origin of the response to adrenal and sex steroids: Roles of promiscuity and co-evolution of enzymes and steroid receptors.   
    See:  Intracellular Receptors

2015    3<73 
Functional Pairing of Class B1 Ligand-GPCR in Cephalochordate Provides Evidence of the Origin of PTH and PACAP/Glucagon Receptor Family.   
    See:   G-Protein Coupled Receptors

2016    2<73   
Evidence for Conservation of the Calcitonin Superfamily and Activity-regulating Mechanisms in the Basal Chordate Branchiostoma floridae: INSIGHTS INTO THE MOLECULAR AND FUNCTIONAL EVOLUTION IN CHORDATES.  

2016    1<73    
RFamide peptides in agnathans and basal chordates.       
Since a peptide with a C-terminal Arg-Phe-NH2 (RFamide peptide) was first identified in the ganglia of the venus clam in 1977, RFamide peptides have been found in the nervous system of both invertebrates and vertebrates. In vertebrates, the RFamide peptide family includes gonadotropin-inhibitory hormone (GnIH), neuropeptide FF (NPFF), prolactin-releasing peptide (PrRP), pyroglutamylated RFamide peptide/26RFamide peptide (QRFP/26RFa), and kisspeptins (kiss1 and kiss2). They are involved in important functions such as the release of hormones, regulation of sexual or social behavior, pain transmission, reproduction, and feeding."   
In basal chordates, namely, in amphioxus (Branchiostoma japonicum), a common ancestral form of GnIH and NPFF genes and their mature peptides, as well as the ortholog of the QRFP gene have been identified. The studies revealed that the number of orthologs of vertebrate RFamide peptides present in agnathans and basal chordates is greater than expected, suggesting that the vertebrate RFamide peptides might have emerged and expanded at an early stage of chordate evolution."  

Amphioxus Hormones
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