A Deletion Truncating the Gonadotropin-Releasing Hormone Gene Is Responsible for Hypogonadism in the
            <i>hpg</i>
            Mouse

Mason, Anthony J.; Hayflick, Joel S.; Zoeller, R. Thomas; Young, W. Scott; Phillips, Heidi S.; Nikolics, Károly; Seeburg, Peter H.

doi:10.1126/science.3024317

Cited by 528 publications

(246 citation statements)

References 27 publications

(37 reference statements)

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“…For example, deleting the mammalian GnRH gene in mice decreased GtH synthesis and disrupted development of reproductive organs (Mason et al, 1986a). Reproductive function was restored to this hypogonadal mouse line after gene therapy or supplementing with exogenous androgen (Mason et al, 1986b;Singh et al, 1995).…”

Section: Introductionmentioning

confidence: 94%

Antisense for gonadotropin-releasing hormone reduces gonadotropin synthesis and gonadal development in transgenic common carp (Cyprinus carpio)

Tang

et al. 2007

Aquaculture

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Section: Introductionmentioning

confidence: 94%

Antisense for gonadotropin-releasing hormone reduces gonadotropin synthesis and gonadal development in transgenic common carp (Cyprinus carpio)

Tang

et al. 2007

Aquaculture

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“…Indeed, it has been known for a long time that a genetic defect in GnRH I secretion in rodents [6] and humans [7,8] results in a substantial decrease in serum gonadotropins associated with hypogonadism, impuberism and infertility. The same phenotype was observed more recently in patients with loss of function mutations in the GnRH type I receptor gene [9].…”

Section: Importance Of the Gnrh I System In Mammalsmentioning

confidence: 99%

Gonadotropin-releasing hormone and the control of gonadotrope function

et al. 2005

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-Normal gametogenesis and steroidogenesis is highly dependent on the pulsatile release of hypothalamic GnRH that binds high-affinity receptors present at the surface of pituitary gonadotrophs thereby triggering the synthesis and release of the gonadotropins LH and FSH. The mammalian GnRH receptor displays the classical heptahelical structure of G protein-coupled receptors with, however, a unique feature, the lack of a C-terminal tail. Accordingly, it does not desensitise sensu stricto, and internalises very poorly. It is now well established that GnRH stimulation induces the activation of a complex network of transduction pathways involved in the control of gonadotropin release and subunit gene expression. Other authors and ourselves have demonstrated that the GnRH action is associated with an increased complexity regarding gene regulation/cell function. Indeed GnRH affects the GnRH receptor gene itself and a number of additional genes that include some involved in cell signalling and auto-/paracrine regulation. The fact that GnRH regulates the expression of its own receptor, together with a host of other genes typically involved in its signal transduction cascades implies alteration/auto-adaptation in gonadotropic responsiveness. Furthermore, some of these genes respond differentially depending on whether the GnRH stimulation is intermittent or permanent suggesting specific roles in the dual process of activation/desensitisation. Thus, it can be assumed that the importance of pulsatility of GnRH action is closely related to, or dependent on, the inability of the GnRH receptor to desensitise. Moreover, multiple post-receptor events are crucial for both the regulation/plasticity of gonadotropic function and the maintenance of cell integrity.

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“…The binding of the hypothalamic decapeptide GnRH to the pituitary GnRHR not only stimulates but is obligatory for the synthesis and secretion of luteinizing hormone (LH) (15,16). In the absence of GnRH input to the pituitary gland, LH production and, consequently, gonadal function in mammals ceases (17,18). Thus, the GnRHR represents the site that mediates the primary stimulatory input to gonadotrope cells.…”

mentioning

confidence: 99%

Constitutive Localization of the Gonadotropin-releasing Hormone (GnRH) Receptor to Low Density Membrane Microdomains Is Necessary for GnRH Signaling to ERK

Navratil

Bliss

Berghorn

et al. 2003

Journal of Biological Chemistry

131

105

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Specialized membrane microdomains known as lipid rafts are thought to contribute to G-protein coupled receptor (GPCR) signaling by organizing receptors and their cognate signaling molecules into discrete membrane domains. To determine if the GnRHR, an unusual member of the GPCR superfamily, partitions into lipid rafts, homogenates of ␣T3-1 cells expressing endogenous GnRHR or Chinese hamster ovary cells expressing an epitope-tagged GnRHR were fractionated through a sucrose gradient. We found the GnRHR and c-raf kinase constitutively localized to low density fractions independent of hormone treatment. Partitioning of c-raf kinase into lipid rafts was also observed in whole mouse pituitary glands. Consistent with GnRH induced phosphorylation and activation of c-raf kinase, GnRH treatment led to a decrease in the apparent electrophoretic mobility of c-raf kinase that partitioned into lipid rafts compared with unstimulated cells. Cholesterol depletion of ␣T3-1 cells using methyl-␤-cyclodextrin disrupted GnRHR but not c-raf kinase association with rafts and shifted the receptor into higher density fractions. Cholesterol depletion also significantly attenuated GnRH but not phorbol ester-mediated activation of extracellular signal-related kinase (ERK) and c-fos gene induction. Raft localization and GnRHR signaling to ERK and c-Fos were rescued upon repletion of membrane cholesterol. Thus, the organization of the GnRHR into low density membrane microdomains appears critical in mediating GnRH induced intracellular signaling.

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A Deletion Truncating the Gonadotropin-Releasing Hormone Gene Is Responsible for Hypogonadism in the hpg Mouse

Cited by 528 publications

References 27 publications

Antisense for gonadotropin-releasing hormone reduces gonadotropin synthesis and gonadal development in transgenic common carp (Cyprinus carpio)

Antisense for gonadotropin-releasing hormone reduces gonadotropin synthesis and gonadal development in transgenic common carp (Cyprinus carpio)

Gonadotropin-releasing hormone and the control of gonadotrope function

Constitutive Localization of the Gonadotropin-releasing Hormone (GnRH) Receptor to Low Density Membrane Microdomains Is Necessary for GnRH Signaling to ERK

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