Functional Divergence of Glycoprotein Hormone Receptors

Two lamprey glycroprotein hormone receptors (lGpH-R I and II) highly similar with gnathostome GpH-Rs were cloned from sea lamprey testes and thyroid, respectively. Vertebrate glycoprotein protein receptors have a large extracellular domain (ED) containing a leu rich domain (LRD) linked to a rhodopsin-like transmembrane domain (TMD) through a highly divergent linker region (signal specificity domain, SSD or \u27hinge\u27 region) and a third major segment, the intracellular domain. To determine the potential roles of the different domains in the activation of the receptor following ligand-receptor binding, functional assays were performed on lGpH-R I/rat luteinizing hormone (LH)-R domain swapped chimeric receptors. These results show that the functional roles of the lamprey glycoprotein-receptor I (lGpH-R I) domains are conserved compared with its Gnathostome homologs. The ability of different glycoprotein hormones to activate chimeric lamprey/rat receptors suggests that the selectivity of the GpH-Rs in respect to their ligands is not controlled exclusively by a single domain but is the result of specific interactions between domains. We hypothesize that these interactions were refined during millions of years of co-evolution of the receptors with their cognate ligands under particular intramolecular, intermolecular and physiological constraints

The Interrelationship of Estrogen Receptor and GnRH in a Basal Vertebrate, the Sea Lamprey

The hypothalamic-pituitary system is considered to be a vertebrate innovation and seminal event that emerged prior to or during the differentiation of the ancestral agnathans. Lampreys are the earliest evolved vertebrates for which there is a demonstrated neuroendocrine system. Lampreys have three hypothalamic gonadotropin-releasing hormones (GnRHs; lGnRH-I, -II, and -III) and two and possibly three pituitary GnRH receptors involved in mediating reproductive processes. Estradiol is considered to be a major reproductive steroid in both male and female lampreys. The purpose of this study was to investigate estrogen receptor (ER) expression in the lamprey brain in adult sea lampreys. Expression of ER mRNA was confirmed in the adult lamprey brain using RT-PCR. Using digoxigenin (DIG)-labeled probes, ER expression was shown to yield moderate, but distinct reaction products in specific neuronal nuclei of the lamprey brain, including the olfactory lobe, hypothalamus, habenular area, and hindbrain. Expression of ER in the hypothalamic area of the brain provides evidence of potential interaction between estradiol and GnRH(s), and is consistent with previous evidence showing estrogen feedback on GnRH in adult lamprey brain. Earlier studies have reported that there is a close distribution of glutamic acid decarboxylase (GAD; GABA-synthesizing enzyme) and lamprey GnRH in the preoptic region in adult lampreys. The establishment of a direct estradiol–kisspeptin–GABA–GnRH interaction in lamprey has yet to be determined and will require future functional and co-localization studies. The phylogenetic position of lampreys as a basal vertebrate allows lampreys to be a basis for understanding the molecular evolution of the neuroendocrine system that arose in the vertebrates

Maturation characteristics and life-history strategies of the Pacific lamprey, Entosphenus tridentatus

Lampreys (Petromyzontiformes) have persisted over millennia and now suffer a recent decline in abundance. Complex life histories may have factored in their persistence; anthropogenic perturbations in their demise. The complexity of life histories of lampreys is not understood, particularly for the anadromous Pacific lamprey, Entosphenus tridentatus Gairdner, 1836. Our goals were to describe the maturation timing and associated characteristics of adult Pacific lamprey, and to test the null hypothesis that different life histories do not exist. Females exhibited early vitellogenesis – early maturation stages; males exhibited spermatogonia – spermatozoa. Cluster analyses revealed an “immature” group and a “maturing–mature” group for each sex. We found statistically significant differences between these groups in the relationships between (i) body mass and total length in males; (ii) Fulton’s condition factor and liver lipids in males; (iii) the gonadosomatic index (GSI) and liver lipids in females; (iv) GSI and total length in females; (v) mean oocyte diameter and liver lipids; and (vi) mean oocyte diameter and GSI. We found no significant difference between the groups in the relationship of muscle lipids and body mass. Our analyses support rejection of the hypothesis of a single life history. We found evidence for an “ocean-maturing” life history that would likely spawn within several weeks of entering fresh water, in addition to the formerly recognized life history of spending 1 year in fresh water prior to spawning—the “stream-maturing” life history. Late maturity, semelparity, and high fecundity suggest that Pacific lamprey capitalize on infrequent opportunities for reproduction in highly variable environments.Keywords: Primitive, Petromyzontiformes, Life histor

Incidence of male intersex in adult Pacific lamprey (Entosphenus tridentatus), with a brief discussion of intersex vs. hermaphroditism in lampreys (Petromyzontiformes)

We report the incidence of male intersex in adult Pacific lamprey (Entosphenus tridentatus (Richardson, 1836)) during their pre-spawning migration in fresh water. Although “hermaphrodites” have been suggested in other adult lampreys, this is the first detailed description and discussion of this phenomenon. A total of 0.5% of our adult Pacific lamprey from Willamette Falls (2 out of 427 adults) were intersex, with oocytes in the testes. This phenomenon was identifiable only by histological examination. The testes of the intersex males were immature, in the beginning stages of meiosis. One intersex male possessed primary growth or perinucleolar stage oocytes loosely interspersed throughout the testes, and the other possessed at least 6 mid-vitellogenic oocytes (0.6 mm, mean long diameter) separate from the testes. Because premetamorphic lamprey can possess both female and male gonial cells, we hypothesize that intersex is a remnant larval trait and that these fish failed to fully develop into males during metamorphosis.Keywords: intersex, maturation, primitive fish, reproduction, cyclostomes., gonochoristicKeywords: intersex, maturation, primitive fish, reproduction, cyclostomes., gonochoristi

Sequencing of the Sea Lamprey (Petromyzon marinus) Genome Provides Insights into Vertebrate Evolution

Lampreys are representatives of an ancient vertebrate lineage that diverged from our own ∼500 million years ago. By virtue of this deeply shared ancestry, the sea lamprey (P. marinus) genome is uniquely poised to provide insight into the ancestry of vertebrate genomes and the underlying principles of vertebrate biology. Here, we present the first lamprey whole-genome sequence and assembly. We note challenges faced owing to its high content of repetitive elements and GC bases, as well as the absence of broad-scale sequence information from closely related species. Analyses of the assembly indicate that two whole-genome duplications likely occurred before the divergence of ancestral lamprey and gnathostome lineages. Moreover, the results help define key evolutionary events within vertebrate lineages, including the origin of myelin-associated proteins and the development of appendages. The lamprey genome provides an important resource for reconstructing vertebrate origins and the evolutionary events that have shaped the genomes of extant organisms

Breaking Dogma on the Hypothalamic-Pituitary Anatomical Relations in Vertebrates

Comment on: Architecture of GnRH-Gonadotrope-Vasculature Reveals a Dual Mode of Gonadotropin Regulation in Fish

Glycoprotein Hormone Receptors in the Sea Lamprey Petromyzon marinus

Secretion of the pituitary glycoprotein hormones (GpH) follitropin, lutropin, and thyrotropin in vertebrates is the main mechanism by which neuroendocrine signals are propagated at the level of the peripheral glands, gonads and thyroid. Receptors of these hormones (glycoprotein hormone receptors, GpH-R) evolved from a common ancestor through gene duplication and subsequent functional divergence during the split of gnathostomes from their agnathan ancestors. Here we review the properties of two novel receptors closely related to gnathostome GpH-Rs identified in the sea lamprey. Although these are the oldest members of this family of receptors described so far in vertebrates, their overall structural features are remarkably close to their mammalian counterparts. However, they cannot be classified unequivocally as either gonadotropin (FSH-R, LH-R) or as thyrotropin receptors (TSH-R) since they share characteristics with both these groups. This may indicate that lamprey receptors reflect in part properties of the ancestral molecule(s) from which all vertebrate GpH-Rs originated. Molecular phylogenetic relationships among gnathostome GpH-Rs are heavily dependent on the functional domain used in analysis. This suggests large variation in functional constraints acting at the level of different segments of the receptor molecule

Integrative neuroendocrine pathways in the control of reproduction in lamprey: a brief review

The gonadotropin-releasing hormone (GnRH) system is well known as the main regulator of reproductive physiology in vertebrates. It is also part of a network of brain structures and pathways that integrate information from the internal and external milieu and coordinate the adaptive behavioral and physiological responses to social and reproductive survival needs. In this paper we review the state of knowledge of the GnRH system in relation to the behavior, external and internal factors that control reproduction in one of the oldest lineage of vertebrates, the lampreys

A role of Histidine(151) in the lamprey gonadotropin-releasing hormone receptor-1 (lGnRHR-1): Functional insight of diverse amino acid residues in the position of Tyr of the DRY motif in GnRHR from an ancestral type II receptor

The highly conserved DRY motif located at the end of the third transmembrane of G-protein-coupled receptors has been described as a key motif for several aspects of GPCR functions. However, in the case of the vertebrate gonadotropin-releasing hormone receptor (GnRHR), the amino acid in the third position in the DRY motif is variable. In the lamprey, a most basal vertebrate, the third amino acid of the DRY in lamprey (lGnRHR-1) is His, while it is most often His/Gln in the type II GnRHR. To investigate the functional significance of the substitution of DRY to DRH in the GnRHR-1, second messenger signaling, ligand binding and internalization of the wild-type and mutant lGnRH receptors were characterized with site-directed mutagenesis. Treatment of the DRE151 and DRS151 mutant receptors with lamprey GnRH-I significantly reduced inositol phosphate compared to wild-type (DRH151) and DRY151 receptors. The Log IC50 of wild-type receptor (-9.554 +/- 0.049) was similar to the Log IC50 of DRE151, DRS151 and DRX151 mutants, yet these same mutants were shown to significantly reduce cell-surface expression. However, the DRY151 mutant compared to the wild-type receptor increased cell-surface expression, suggesting that the reduction of IP production was due to the level of the cell-surface expression of the mutant receptors. The rate of internalization of DRX151 (35.60%) was reduced compared to wild-type and other mutant receptors. These results suggest that His(151) of the lamprey GnRH receptor-1 may play a critical role in the retention of a certain level of cell-surface expression for subsequent cellular second messenger events. (C) 2009 Elsevier Inc. All rights reserved