scholarly journals Learning New Tricks from an Old Dog: The Processing of the Intracellular Precursor of the Luteinizing Hormone Receptor (LHR) into the Mature Cell-Surface LHR Is a Regulated Process

Endocrinology ◽  
2005 ◽  
Vol 146 (8) ◽  
pp. 3221-3223 ◽  
Author(s):  
Mario Ascoli
Keyword(s):  
Luteinizing Hormone ◽  
Cell Surface ◽  
Hormone Receptor ◽  
Luteinizing Hormone Receptor ◽  
Mature Cell

scholarly journals Constitutive Activating and Inactivating Mutants of Eel Luteinizing Hormone Receptor

2020 ◽  
Author(s):  
Munkhzaya Byambaragchaa ◽  
Dong-An Kim ◽  
Dae-Jung Kim ◽  
Sun-Mee Hong ◽  
Myung-Hwa Kang ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Luteinizing Hormone ◽  
Cell Surface ◽  
Hormone Receptor ◽  
Luteinizing Hormone Receptor ◽  
Cell Surface Receptors ◽  
Wild Type ◽  
Surface Receptors ◽  
Agonist Stimulation ◽  
In Cells

We analyzed signal transduction of three constitutively activating mutants (M410T, L469R, and D590Y) and two inactivating mutants (D417N and Y558F) of the eel luteinizing hormone receptor (eel LHR), known to occur in human LHR. The objective of this study was to assess the functional effects of these mutations in signal transduction and cell surface loss of receptor. Mutant receptors were transiently expressed in Chinese hamster ovary (CHO-K1) cells. Eel LH-stimulated accumulation of cyclic adenosine monophosphate (cAMP) was measured by homogeneous time-resolved fluorescence (HTRF) assays. The loss of receptors from the cells surface was measured using an enzyme-linked immunosorbent assay (ELISA) in human embryonic kidney (HEK) 293 cells. The cAMP response in cells expressing the wild type eel LHR was increased in a dose-dependent manner using eel LH ligand stimulation. Compared with the wild type, cells expressing the activating mutants (M410T, L469R, and D590Y), exhibited a 4.0-, 19.1-, and 7.8-fold increase in basal cAMP response without agonist stimulation, respectively. Their maximal responses to agonist stimulation were approximately 65%, 52%, and 98%, respectively, of those of the wild type. The inactivating mutants (D417N and Y558F) did not completely impair signal transduction, and their maximal responses were only 33% and25 % of those of wild type. These data clearly showed that the eel LHR-L469R and D590Y, activating mutants enhanced the rate of the loss of cell surface receptors following treatment with eel LH. Thus, the loss of cell surface receptors in cells expressing mutant eel LHRs was consistent with the eel LH agonist-induced production of cAMP. Our results suggested that the activation of the eel LHR requires appropriate loss of LHR-ligand complexes from the cell surface.

scholarly journals Luteinizing Hormone Receptor Ectodomain Splice Variant Misroutes the Full-Length Receptor into a Subcompartment of the Endoplasmic Reticulum

2006 ◽  
Vol 17 (5) ◽  
pp. 2243-2255 ◽  
Author(s):  
Pirjo M. Apaja ◽  
Jussi T. Tuusa ◽  
E. Maritta Pietilä ◽  
Hannu J. Rajaniemi ◽  
Ulla E. Petäjä-Repo
Keyword(s):  
Endoplasmic Reticulum ◽  
Luteinizing Hormone ◽  
Cell Surface ◽  
Hormone Receptor ◽  
Splice Variant ◽  
Secretory Pathway ◽  
Signal Sequence ◽  
Full Length ◽  
Luteinizing Hormone Receptor ◽  
Hormone Binding

The luteinizing hormone receptor (LHR) is a G protein–coupled receptor that is expressed in multiple RNA messenger forms. The common rat ectodomain splice variant is expressed concomitantly with the full-length LHR in tissues and is a truncated transcript corresponding to the partial ectodomain with a unique C-terminal end. Here we demonstrate that the variant alters the behavior of the full-length receptor by misrouting it away from the normal secretory pathway in human embryonic kidney 293 cells. The variant was expressed as two soluble forms of Mr 52,000 and Mr 54,000, but although the protein contains a cleavable signal sequence, no secretion to the medium was observed. Only a very small fraction of the protein was able to gain hormone-binding ability, suggesting that it is retained in the endoplasmic reticulum (ER) by its quality control due to misfolding. This was supported by the finding that the variant was found to interact with calnexin and calreticulin and accumulated together with these ER chaperones in a specialized juxtanuclear subcompartment of the ER. Only proteasomal blockade with lactacystin led to accumulation of the variant in the cytosol. Importantly, coexpression of the variant with the full-length LHR resulted in reduction in the number of receptors that were capable of hormone binding and were expressed at the cell surface and in targeting of immature receptors to the juxtanuclear ER subcompartment. Thus, the variant mediated misrouting of the newly synthesized full-length LHRs may provide a way to regulate the number of cell surface receptors.

Luteinizing hormone receptor

2007 ◽  
Author(s):  
Thomas Buech ◽  
Pascal Nurwakagari ◽  
David Ben-Menahem ◽  
Thomas Gudermann
Keyword(s):  
Luteinizing Hormone ◽  
Hormone Receptor ◽  
Luteinizing Hormone Receptor

scholarly journals Possible Relevance of Soluble Luteinizing Hormone Receptor during Development and Adulthood in Boys and Men

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1329
Author(s):  
Li Juel Mortensen ◽  
Mette Lorenzen ◽  
Anne Jørgensen ◽  
Jakob Albrethsen ◽  
Niels Jørgensen ◽  
...  
Keyword(s):  
Luteinizing Hormone ◽  
Hormone Receptor ◽  
Adrenal Glands ◽  
Seminal Fluid ◽  
Body Fluids ◽  
Luteinizing Hormone Receptor ◽  
Gonadal Function ◽  
Fetal Kidney ◽  
Healthy Men ◽  
Human Fetal Kidney

Luteinizing hormone (LH) and human chorionic gonadotropin (hCG) are agonists for the luteinizing hormone receptor (LHCGR) which regulates male reproductive function. LHCGR may be released into body fluids. We wish to determine whether soluble LHCGR is a marker for gonadal function. Cross-sectional, longitudinal, and intervention studies on 195 healthy boys and men and 396 men with infertility, anorchia, or Klinefelter Syndrome (KS) were used to correlate LHCGR measured in serum, seminal fluid, urine, and hepatic/renal artery and vein with gonadal function. LHCGR was determined in fluids from in vitro and in vivo models of human testicular tissue and cell lines, xenograft mouse models, and human fetal kidney and adrenal glands. Western blot showed LHCGR fragments in serum and gonadal tissue of similar size using three different antibodies. The LHCGR-ELISA had no species cross-reactivity or unspecific reaction in mouse serum even after human xenografting. Instead, sLHCGR was released into the media after the culture of a human fetal kidney and adrenal glands. Serum sLHCGR decreased markedly during puberty in healthy boys (p = 0.0001). In healthy men, serum sLHCGR was inversely associated with the Inhibin B/FSH ratio (β −0.004, p = 0.027). In infertile men, seminal fluid sLHCGR was inversely associated with serum FSH (β 0.006, p = 0.009), sperm concentration (β −3.5, p = 0.003) and total sperm count (β −3.2, p = 0.007). The injection of hCG lowered sLHCGR in serum and urine of healthy men (p < 0.01). In conclusion, sLHCGR is released into body-fluids and linked with pubertal development and gonadal function. Circulating sLHCGR in anorchid men suggests that sLHCGR in serum may originate from and possibly exert actions in non-gonadal tissues. (ClinicalTrials: NTC01411527, NCT01304927, NCT03418896).

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