Signaling by G-protein-coupled receptor (GPCR): Studies on the GnRH receptor

Naor, Zvi

doi:10.1016/j.yfrne.2008.07.001

Cited by 277 publications

(254 citation statements)

References 336 publications

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“…The two peptides are identical in rat and man [19]. GnRH1 is a hormone which regulates the hypothalamic-pituitary axis and gonadotropin production [1,2,3], whereas GnRH2 is a neuropeptide expressed in the brain, in particular hind brain and spinal cord, hence being extra-hypothalamic [20]. GnRH2 is believed to participate in the reproduction and sexual behavior through neuro-modulation [19,21].…”

Section: Discussionmentioning

confidence: 99%

“…Continuous treatment with the GnRH analog leuprolide was shown to improve symptoms in patients with functional bowel disorders [30,31]. The mechanism behind is enigmatic, but may be due to down-regulation of the GnRH-R in the pituitary gland and subsequent depletion of gonadotropins and sex hormones [3], suggested to influence gastrointestinal motility [32,33]. Another plausible explanation to the leuprolide-induced effects is by activation of intestinal GnRH-R.…”

Section: Discussionmentioning

confidence: 99%

“…Via the portal circulation it reaches the anterior pituitary and stimulates secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) through GnRH receptor (GnRH-R) activation [1,2]. The gonadotropins target the gonads and regulate secretion of steroid hormones, like estrogen and progesterone [3]. During the last years, several studies have described effects by these hormones also on the gastrointestinal tract.…”

Section: Introductionmentioning

confidence: 99%

“…During the last years, several studies have described effects by these hormones also on the gastrointestinal tract. GnRH analogs have been shown to inhibit gastric secretion and gastrin release in rat and dog [4,5], to inhibit cell proliferation of gastric epithelium [6] and smooth muscle cells [7], and to induce apoptosis and inhibit cell proliferation in gastric cancer cells [3,8]. Both GnRH analogs and LH have been shown to affect gastrointestinal motility in rat and man; GnRH analogs by stimulation of gastrointestinal motility and LH by prolonging and fragmenting of the phase III migrating motor complex (MMC) [9,10,11].…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Expression and distribution of GnRH, LH, and FSH and their receptors in gastrointestinal tract of man and rat

Sand

Bergvall

Ekblad

et al. 2013

Regulatory Peptides

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Expression and distribution of GnRH, LH, and FSH and their receptors in gastrointestinal tract of man and rat

Sand

Bergvall

Ekblad

et al. 2013

Regulatory Peptides

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“…GnRH specifically binds to the corresponding GnRH receptor expressed on pituitary gonadotropes, and subsequently stimulates cells to synthesize and release secretory products including two gonadotropins (for reviews see: Bliss et al, 2010;Naor, 2009;Ruf et al, 2003). Castration of experimental animals increases the intrinsic GnRH level released from hypothalamic neurons by impairing the negative feedback control of gonadal sex steroids (Pielecka and Moenter, 2006).…”

Section: Influences Of Extrinsic Stimuli To the Gnrh Receptor On The mentioning

confidence: 99%

Functional implications of the Golgi and microtubular network in gonadotropes

Watanabe

Bochimoto

Koga

et al. 2014

Molecular and Cellular Endocrinology

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In contrast to the widely accepted images of the Golgi apparatus as a cup-like shape, the Golgi in pituitary gonadotropes is organized as a spherical shape in which the outer and inner faces are cis-and trans-Golgi elements, respectively. At the center of the spherical Golgi, a pair of centrioles is situated as a microtubule-organizing center from which radiating microtubules isotropically extend toward the cell periphery. This review focuses on the significance of the characteristic organization of the Golgi and microtubule network in gonadotropes, considering the roles of microtubule-dependent membrane transport in the formation and maintenance of the Golgi structure. Because the highly symmetrical organization of the Golgi is possibly perturbed in response to experimental treatments of gonadotropes, monitoring of the Golgi structure in gonadotropes under various experimental conditions will be a novel in vivo approach to elucidate the biogenesis of the Golgi apparatus.

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Enzymatic stability, solution structure, and antiproliferative effect on prostate cancer cells of leuprolide and new gonadotropin-releasing hormone peptide analogs

et al. 2011

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Analogs of GnRH, including [DLeu6, desGly1o]-GnRH-NHEt (leuprolide, commercial product), have been widely used in oncology to induce reversible chemical castration. Several studies have provided evidence that, besides their pituitary effects, GnRH analogs may exert direct antiproliferative effects on tumor cells. To study the effect of modifications in positions 4 and 6 of leuprolide on prostate cancer cell proliferation, we synthesized 12 new leuprolide analogs. All GnRH analogs lacked the carboxy-terminal Gly10-amide of GnRH, and an ethylamide residue was added to Pro9. Gly6 was substituted by DLys, Nepsilon-modified DLys, Glu, and DGlu. To improve the enzymatic stability, NMeSer was incorporated in position 4, and the rate of hydrolysis by alpha-chymotrypsin and subtilisin was investigated. Our results demonstrate that this incorporation increases enzymatic stability in all analogs of GnRH, whereas the antiproliferative effect on PC3 and LNCaP prostate cancer cells is similar to that of leuprolide. Conformational studies were performed to elucidate structural changes occurring on substitution of native residues and to study structure-activity relationship for these analogs. The solution models of [DLeu6, desGly10]-GnRH-NHEt (leuprolide), [NMeSer4, DGlu6, desGly10]-GnRH-NHEt, [Glu6, desGly10]-GnRH-NHEt, and [DGIu6, desGly10]-GnRH-NHEt peptides were determined through two-dimensional nuclear magnetic resonance spectroscopy in dimethylsulfoxide. Nuclear magnetic resonance data provide experimental evidence for the U-turn-like structure appeared in all four analogs, which could be characterized as beta-hairpin conformation. The most stable analog [NMeSer4, DGlu6, desGly10]-GnRH-NHEt against proteolytic cleavage forms a second extra backbone turn observed for residues 1-4.

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Signaling by G-protein-coupled receptor (GPCR): Studies on the GnRH receptor

Cited by 277 publications

References 336 publications

Expression and distribution of GnRH, LH, and FSH and their receptors in gastrointestinal tract of man and rat

Expression and distribution of GnRH, LH, and FSH and their receptors in gastrointestinal tract of man and rat

Functional implications of the Golgi and microtubular network in gonadotropes

Enzymatic stability, solution structure, and antiproliferative effect on prostate cancer cells of leuprolide and new gonadotropin-releasing hormone peptide analogs

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