scholarly journals Functional Characterization of GH-Like Homolog in Amphioxus Reveals an Ancient Origin of GH/GH Receptor System

Endocrinology ◽  
2014 ◽  
Vol 155 (12) ◽  
pp. 4818-4830 ◽  
Author(s):  
Mengyang Li ◽  
Zhan Gao ◽  
Dongrui Ji ◽  
Shicui Zhang

Amphioxus belongs to the subphylum cephalochordata, an extant representative of the most basal chordates. Despite many studies on the endocrine system of amphioxus, no evidence showed the presence of pituitary hormones. In this study, we clearly demonstrated the existence of a functional GH-like hormone in amphioxus, which is able to bind purified GH receptors, stimulate IGF-I expression, promote growth rate of fish, and rescue embryonic defects caused by a shortage of GH. We also showed the presence of a GH/prolactin-like-binding protein containing the entire hormone binding domain of GH/prolactin receptors in amphioxus, which is widely expressed among tissues, and interacts with the GH-like hormone. It is clear from these results that the GH/GH receptor-like system is present in amphioxus and, hence, in all classes of chordates. Notably, the GH-like hormone appears to be the only member of the vertebrate pituitary hormones family in amphioxus, suggesting that the hormone is the ancestral peptide that originated first in the molecular evolution of the pituitary hormones family in chordates. These data collectively suggest that a vertebrate-like neuroendocrine axis setting has already emerged in amphioxus, which lays a foundation for subsequent formation of hypothalamic-pituitary system in vertebrates.

2019 ◽  
Vol 62 (12) ◽  
pp. 1655-1669
Author(s):  
Peng Wang ◽  
Meng Wang ◽  
Liping Zhang ◽  
Shenjie Zhong ◽  
Wanyue Jiang ◽  
...  

1999 ◽  
Vol 84 (3) ◽  
pp. 1011-1016
Author(s):  
Keiji Iida ◽  
Yutaka Takahashi ◽  
Hidesuke Kaji ◽  
Michiko Okazaki Takahashi ◽  
Yasuhiko Okimura ◽  
...  

2007 ◽  
Vol 92 (8) ◽  
pp. 2893-2901 ◽  
Author(s):  
Vibor Petkovic ◽  
Amélie Besson ◽  
Mario Thevis ◽  
Didier Lochmatter ◽  
Andrée Eblé ◽  
...  

Abstract Context and Objective: A single missense mutation in the GH-1 gene converting codon 77 from arginine (R) to cysteine (C) yields a mutant GH-R77C peptide, which was described as natural GH antagonist. Design, Setting, and Patients: Heterozygosity for GH-R77C/wt-GH was identified in a Syrian family. The index patient, a boy, was referred for assessment of his short stature (−2.5 sd score) and partial GH insensitivity was diagnosed. His mother and grandfather were also carrying the same mutation and showed partial GH insensitivity with modest short stature. Interventions and Results: Functional characterization of the GH-R77C was performed through studies of GH receptor binding and activation of Janus kinase 2/Stat5 pathway. No differences in the binding affinity and bioactivity between wt-GH and GH-R77C were found. Similarly, cell viability and proliferation after expression of both GH peptides in AtT-20 cells were identical. Quantitative confocal microscopy analysis revealed no significant difference in the extent of subcellular colocalization between wt-GH and GH-R77C with endoplasmic reticulum, Golgi, or secretory vesicles. Furthermore studies demonstrated a reduced capability of GH-R77C to induce GHR/GHBP gene transcription rate when compared with wt-GH. Conclusion: Reduced GH receptor/GH-binding protein expression might be a possible cause for the partial GH insensitivity with delay in growth and pubertal development found in our patients. In addition, this group of patients deserves further attention because they could represent a distinct clinical entity underlining that an altered GH peptide may also have a direct impact on GHR/GHBP gene expression causing partial GH insensitivity.


2020 ◽  
Vol 477 (7) ◽  
pp. 1261-1286 ◽  
Author(s):  
Marie Anne Richard ◽  
Hannah Pallubinsky ◽  
Denis P. Blondin

Brown adipose tissue (BAT) has long been described according to its histological features as a multilocular, lipid-containing tissue, light brown in color, that is also responsive to the cold and found especially in hibernating mammals and human infants. Its presence in both hibernators and human infants, combined with its function as a heat-generating organ, raised many questions about its role in humans. Early characterizations of the tissue in humans focused on its progressive atrophy with age and its apparent importance for cold-exposed workers. However, the use of positron emission tomography (PET) with the glucose tracer [18F]fluorodeoxyglucose ([18F]FDG) made it possible to begin characterizing the possible function of BAT in adult humans, and whether it could play a role in the prevention or treatment of obesity and type 2 diabetes (T2D). This review focuses on the in vivo functional characterization of human BAT, the methodological approaches applied to examine these features and addresses critical gaps that remain in moving the field forward. Specifically, we describe the anatomical and biomolecular features of human BAT, the modalities and applications of non-invasive tools such as PET and magnetic resonance imaging coupled with spectroscopy (MRI/MRS) to study BAT morphology and function in vivo, and finally describe the functional characteristics of human BAT that have only been possible through the development and application of such tools.


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