Evidence for Tight Coupling of Gonadotropin-Releasing Hormone Receptors to Phosphatidylinositol Kinase in Plasma Membrane from Ovarian Carcinomas

1995 ◽  
Vol 58 (1) ◽  
pp. 110-115 ◽  
Author(s):  
Hiroshi Takagi ◽  
Atsushi Imai ◽  
Tatsuro Furui ◽  
Shinji Horibe ◽  
Tatsuo Fuseya ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Hormone Receptors ◽  
Gonadotropin Releasing Hormone ◽  
Tight Coupling ◽  
Ovarian Carcinomas ◽  
Releasing Hormone ◽  
Phosphatidylinositol Kinase

scholarly journals Calnexin regulated gonadotropin-releasing hormone receptor plasma membrane expression

2006 ◽  
Vol 37 (3) ◽  
pp. 479-488 ◽  
Author(s):  
Shaun P Brothers ◽  
Jo Ann Janovick ◽  
P Michael Conn
Keyword(s):  
Plasma Membrane ◽  
Hormone Receptors ◽  
Phosphorylation Site ◽  
Significant Proportion ◽  
Retention Mechanism ◽  
Gonadotropin Releasing Hormone ◽  
Physical Interaction ◽  
Membrane Expression ◽  
Releasing Hormone ◽  
Plasma Membrane Expression

A significant proportion of human gonadotropin-releasing hormone receptors (GnRHRs) are normally retained in the endoplasmic reticulum (ER); however, nearly all rat GnRHRs are routed to the plasma membrane. When mutations are introduced into either receptor, considerably more of the proteins are recognized by the quality control system (QCS) as misfolded and retained compared with wild-type (WT) receptor, resulting in decreased signaling in the presence of agonist. Calnexin, a component of the QCS, decreased plasma membrane expression of the GnRHRs, an effect that was mediated by a physical interaction between the receptor and the calnexin. Only the human receptor showed reduced signaling because it had fewer spare receptors compared with the rat GnRHR, allowing calnexin to affect signaling. Calnexin did not affect receptor signaling when K191 was deleted from the human WT GnRHR. Removal of this amino acid decreases receptor misfolding and increases plasma membrane expression. K191 is not present in the rat WT GnRHR. A pharmacological chaperone that corrects GnRHR misfolding, increased expression of the human WT GnRHR in the presence of calnexin. Calnexin apparently retains misfolded GnRHRs but routes correctly folded receptors to the plasma membrane. Mutation of a calnexin protein kinase C consensus phosphorylation site promoted increased retention of the human GnRHR, suggesting that calnexin phosphorylation controls the retention mechanism. We conclude that a proportion of the human and the rat WT GnRHR appears to be retained in the ER by calnexin, an effect that decreases GnRHR signaling capacity.

scholarly journals Intracellular gonadotropin-releasing hormone receptors in breast cancer and gonadotrope lineage cells

2006 ◽  
Vol 191 (3) ◽  
pp. 625-636 ◽  
Author(s):  
Kathleen R Sedgley ◽  
Ann R Finch ◽  
Christopher J Caunt ◽  
Craig A McArdle
Keyword(s):  
Plasma Membrane ◽  
Cell Surface ◽  
Hormone Receptors ◽  
Gonadotropin Releasing Hormone ◽  
Type I ◽  
Type Ii ◽  
Cell Type ◽  
Mcf7 Cells ◽  
Inhibition Of Proliferation ◽  
Releasing Hormone

Gonadotropin-releasing hormone receptors (GnRHRs) are expressed in gonadotropes and several extra-pituitary sites. They are assumed to be cell surface proteins but the human (h) GnRHR lacks features favoring plasma membrane localization and receptor location varies with cell type. When expressed in mammary (MCF7) cells, cell surface hGnRHR binding was much lower than that of mouse and sheep GnRHRs (type I GnRHRs without C-terminal tails), Xenopus (X) and marmoset type II GnRHRs (type II GnRHRs with C-tails) or chimeric receptors (type I GnRHRs with added XGnRHR C-tails). hGnRHR binding was higher in αT4 (gonadotrope-derived) cells and was increased less by C-tail addition. Whole cell levels of tagged human, Xenopus and chimeric GnRHRs were comparable (Western blotting) and confocal microscopy revealed that the hGnRHR is primarily intracellular (distribution similar to the endoplasmic reticulum marker, calreticulin), whereas most XGnRHR is at the plasma membrane, and adding the C-tail increased cell surface hGnRHR levels. A membrane-permeant antagonist increased cell surface hGnRHR number (>4-fold, t½ = 4 h) and also increased hGnRHR signaling and hGnRHR-mediated inhibition of proliferation. A more rapid increase in hGnRHR binding occurred when the temperature was raised from 4 to 37 °C (>5-fold, t½ = 15 min) and this effect was prevented by mutation to prevent signaling. Thus, cell surface GnRHR expression depends on receptor and cell type and the hGnRHR is primarily an intracellular protein that traffics to the cell surface for signaling in MCF7 cells. Manipulations favoring such trafficking may facilitate selective targeting of extra-pituitary GnRHRs.

scholarly journals Endocrine and molecular milieus of ovarian follicles are diversely affected by human chorionic gonadotropin and gonadotropin-releasing hormone in prepubertal and mature gilts

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Adam J. Ziecik ◽  
Jan Klos ◽  
Katarzyna Gromadzka-Hliwa ◽  
Mariola A. Dietrich ◽  
Mariola Slowinska ◽  
...  
Keyword(s):  
Chorionic Gonadotropin ◽  
Human Chorionic Gonadotropin ◽  
Hormone Receptors ◽  
Cell Function ◽  
Ovarian Follicle ◽  
Molecular Transport ◽  
Gonadotropin Releasing Hormone ◽  
Matrix Remodeling ◽  
Releasing Hormone ◽  
Serum Gonadotropin

AbstractDifferent strategies are used to meet optimal reproductive performance or manage reproductive health. Although exogenous human chorionic gonadotropin (hCG) and gonadotropin-releasing hormone (GnRH) agonists (A) are commonly used to trigger ovulation in estrous cycle synchronization, little is known about their effect on the ovarian follicle. Here, we explored whether hCG- and GnRH-A-induced native luteinizing hormone (LH) can affect the endocrine and molecular milieus of ovarian preovulatory follicles in pigs at different stages of sexual development. We collected ovaries 30 h after hCG/GnRH-A administration from altrenogest and pregnant mare serum gonadotropin (eCG)-primed prepubertal and sexually mature gilts. Several endocrine and molecular alternations were indicated, including broad hormonal trigger-induced changes in follicular fluid steroid hormones and prostaglandin levels. However, sexual maturity affected only estradiol levels. Trigger- and/or maturity-dependent changes in the abundance of hormone receptors (FSHR and LHCGR) and proteins associated with lipid metabolism and steroidogenesis (e.g., STAR, HSD3B1, and CYP11A1), prostaglandin synthesis (PTGS2 and PTGFS), extracellular matrix remodeling (MMP1 and TIMP1), protein folding (HSPs), molecular transport (TF), and cell function and survival (e.g., VIM) were observed. These data revealed different endocrine properties of exogenous and endogenous gonadotropins, with a potent progestational/androgenic role of hCG and estrogenic/pro-developmental function of LH.

Demonstration of gonadotropin releasing-hormone receptors on gonadotrophs and somatotrophs of the goldfish: an electron microscope study

1991 ◽  
Vol 36 (3) ◽  
pp. 369-378 ◽  
Author(s):  
Harry Cook ◽  
John W. Berkenbosch ◽  
Mark J. Fernhout ◽  
Kei-Li Yu ◽  
Richard E. Peter ◽  
...  
Keyword(s):  
Electron Microscope ◽  
Microscope Study ◽  
Electron Microscope Study ◽  
Hormone Receptors ◽  
Gonadotropin Releasing Hormone ◽  
Releasing Hormone

Gonadotropin-Releasing Hormone Receptors and Signaling

2021 ◽  
pp. 149-181
Author(s):  
Craig A. McArdle ◽  
Margaritis Voliotis ◽  
Krasimira Tsaneva-Atanasova ◽  
Robert C. Fowkes
Keyword(s):  
Hormone Receptors ◽  
Gonadotropin Releasing Hormone ◽  
Releasing Hormone

scholarly journals Effects of Gonadotropin-Releasing Hormone (GnRH) and Its Analogues on the Physiological Behaviors and Hormone Content of Tetrahymena pyriformis

2019 ◽  
Vol 20 (22) ◽  
pp. 5711
Author(s):  
Eszter Lajkó ◽  
Éva Pállinger ◽  
Zsombor Kovács ◽  
Ildikó Szabó ◽  
László Kőhidai
Keyword(s):  
Hormone Receptors ◽  
Tetrahymena Pyriformis ◽  
Gonadotropin Releasing Hormone ◽  
Dependent Manner ◽  
Releasing Hormone ◽  
Hormone Content ◽  
Endogenous Histamine ◽  
Swimming Pattern ◽  
Recognition Ability ◽  
Cell Counter

The unicellular Tetrahymena distinguishes structure-related vertebrate hormones by its chemosensory reactions. In the present work, the selectivity of hormone receptors was evaluated by analyzing the effects of various gonadotropin-releasing hormone (GnRH) analogs (GnRH-I, GnRH-III) as well as truncated (Ac-SHDWKPG-NH2) and dimer derivatives ([GnRH-III(C)]2 and [GnRH-III(CGFLG)]2) of GnRH-III on (i) locomotory behaviors, (ii) cell proliferation, and (iii) intracellular hormone contents of Tetrahymena pyriformis. The migration, intracellular hormone content, and proliferation of Tetrahymena were investigated by microscope-assisted tracking analysis, flow cytometry, and a CASY TT cell counter, respectively. Depending on the length of linker sequence between the two GnRH-III monomers, the GnRH-III dimers had the opposite effect on Tetrahymena migration. [GnRH-III(CGFLG)]2 dimer had a slow, serpentine-like movement, while [GnRH-III(C)]2 dimer had a rather linear swimming pattern. All GnRH-III derivatives significantly induced cell growth after 6 h incubation. Endogenous histamine content was uniformly enhanced by Ac-SHDWKPG-NH2 and GnRH-III dimers, while some differences between the hormonal activities of GnRHs were manifested in their effects on intracellular levels of serotonin and endorphin. The GnRH peptides could directly affect Tetrahymena migration and proliferation in a structure-dependent manner, and they could indirectly regulate these reactions by paracrine/autocrine mechanisms. Present results support the theory that recognition ability and selectivity of mammalian hormone receptors can be deduced from a phylogenetically ancient level like the unicellular Tetrahymena.

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