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Waljit S Dhillo - One of the best experts on this subject based on the ideXlab platform.

  • kisspeptin and fertility
    Journal of Endocrinology, 2011
    Co-Authors: Saira Hameed, Channa N Jayasena, Waljit S Dhillo
    Abstract:

    The kisspeptins are af amilyof peptide hormones, which in recent years have been shown to play a critical role in the regulation of the hypothalamic–pituitary–gonadal Axis, thus in turn influencing fertility and reproduction. This review examines the physiological role of kisspeptin and the kisspeptin receptor in the control of gonadotrophin and gonadal steroid hormone secretion and the implications of these findings with respect to fertility. In addition, the potential therapeutic use of kisspeptin in the treatment of reproductive disorders will be examined.

  • kisspeptin 54 stimulates the hypothalamic pituitary gonadal Axis in human males
    Obstetrical & Gynecological Survey, 2007
    Co-Authors: Waljit S Dhillo, Emily L Thompson, Kevin G Murphy, Michael Patterson, Owais B. Chaudhri, Vian Amber, Michael K Badman, Barbara M Mcgowan, Sejal R Patel
    Abstract:

    Kisspeptin is a 54-amino acid peptide that activates the G protein-coupled receptor GPR54. This system appears to be an important regulator of reproduction. Mutation of GPR54 is associated with failed reproductive function. Studies in rodents and primates indicate that the endogenous neuropeptide agonist for GPR54, kisspeptin, strongly stimulates the Hypothalamic-Pituitary-Gonadal Axis. This double-blind, placebo-controlled, crossover study examined the effects of elevated circulating levels of kisspeptin on testosterone and gonadotropin concentrations in six males who received 90-minute intravenous infusions of 4 pmol/kg/minute of kisspeptin-54 and physiological saline in random order. Increasing infusion rates of kisspeptin-54 led to a dose-dependent rise in mean plasma kisspeptin immunoreactivity (IR). A dose-dependent increase in luteinizing hormone (LH) levels also was documented. Mean levels of follicle-stimulating hormone (FSH) also increased over time as kisspeptin-54 was infused, and there was a trend toward increased plasma testosterone levels. The increases in FSH and testosterone, however, were not dose-dependent. Elevations in circulating levels of LH, FSH, and testosterone were significant compared with responses to saline infusion. Infusion of kisspeptin-54 had no effect on the release of inhibin B or on sexual arousal scores. The course of kisspeptin-IR after reaching a plateau level followed first-order kinetics with a plasma half-life of 27 minutes, a mean metabolic clearance rate of 3.2 m/kg/minute, and a volume of distribution of 128 ml/kg. Systemic administration of kisspeptin-54 acutely increases circulating levels of gonadotropins and testosterone in human males. This potentially provides a novel means of manipulating the Hypothalamic-Pituitary-Gonadal Axis in patients with reproductive disorders.

  • kisspeptin 54 stimulates the hypothalamic pituitary gonadal Axis in human males
    The Journal of Clinical Endocrinology and Metabolism, 2005
    Co-Authors: Waljit S Dhillo, Emily L Thompson, Kevin G Murphy, Michael Patterson, Owais B. Chaudhri, Vian Amber, Michael K Badman, Barbara M Mcgowan, Sejal R Patel, Mohammad A. Ghatei
    Abstract:

    Context: Mutation of the G protein-coupled receptor 54 is associated with a failure of reproductive function. The endogenous neuropeptide agonist for G protein-coupled receptor 54, kisspeptin, potently stimulates the Hypothalamic-Pituitary-Gonadal Axis in rodents and primates. Objective: The present study was designed to determine the effects of elevating circulating kisspeptin levels on LH, FSH, and testosterone in male volunteers. Design: This was a double-blind, placebo-controlled, crossover study. Setting: This was a hospital-based study. Participants: Male volunteers (n = 6) were recruited. Interventions: Each volunteer received a 90-min iv infusion of kisspeptin-54 (4 pmol/kg·min) and a control infusion of saline (0.9%) in random order. Main Outcome Measure: Plasma LH, FSH, and testosterone concentrations were measured. Results: Kisspeptin-54 infusion significantly increased plasma LH, FSH, and testosterone concentrations compared with saline infusion (mean 90-min LH: kisspeptin, 10.8 ± 1.5 vs. sali...

  • central and peripheral administration of kisspeptin 10 stimulates the hypothalamic pituitary gonadal Axis
    Journal of Neuroendocrinology, 2004
    Co-Authors: Emily L Thompson, Mohammad A. Ghatei, Michael Patterson, J F Todd, K Murphy, Kirsty L Smith, Waljit S Dhillo, S R Bloom
    Abstract:

    Kisspeptin is the peptide product of the KiSS-1 gene and the endogenous agonist for the GPR54 receptor. Recent evidence suggests the kisspeptin/GPR54 system is a key regulator of the reproductive system. We examined the effect of intracerebroventricular (i.c.v.) and peripheral administration of the active kisspeptin fragment, kisspeptin-10, on circulating gonadotrophins and total testosterone levels in adult male rats. The effect of kisspeptin-10 in vitro on the release of hypothalamic peptides from hypothalamic explants and gonadotrophins from anterior pituitary fragments was also determined. The i.c.v. administration of kisspeptin-10 dose-dependently increased plasma luteinizing hormone (LH) and increased plasma follicle stimulating hormone (FSH) and total testosterone at 60 min postinjection. In a separate study investigating the time course of this response, i.c.v. administered kisspeptin-10 (3 nmol) significantly increased plasma LH at 10, 20 and 60 min, FSH at 60 min and total testosterone at 20 and 60 min postinjection. Kisspeptin-10 stimulated the release of luteinizing hormone-releasing hormone (LHRH) from in vitro hypothalamic explants. Peripheral administration of kisspeptin-10 increased plasma LH, FSH and total testosterone. However, doses of 100–1000 nM kisspeptin-10 did not influence LH or FSH release from pituitary fragments in vitro. Kisspeptin therefore potently stimulates the Hypothalamic-Pituitary-Gonadal Axis. These effects are likely to be mediated via the hypothalamic LHRH system.

Mohammad A. Ghatei - One of the best experts on this subject based on the ideXlab platform.

  • The in vitro role of tumour necrosis factor-alpha and interleukin-6 in the hypothalamic-pituitary gonadal Axis.
    Journal of Neuroendocrinology, 2008
    Co-Authors: S. H. Russell, Mohammad A. Ghatei, Caroline J. Small, Sarah A. Stanley, Stephen Franks, S R Bloom
    Abstract:

    The adipocyte derived hormone leptin has been implicated as an important nutritional signal to the reproductive system, but the role of other adipocyte related cytokines is not clear. Tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6 are present in adipose tissue and released into the circulation where plasma levels correlate positively with body mass index and body fat mass. These cytokines could play a role in signalling nutritional status to the Hypothalamic-Pituitary-Gonadal Axis. We investigated the effects of TNF-alpha and IL-6 on basal and luteinizing hormone releasing hormone (LHRH) stimulated luteineizing hormone (LH) release from cultured anterior pituitary cells, harvested from either proestrus female or male Wistar rats. We examined the effects of TNF-alpha and IL-6 on LHRH release from hypothalamic explants harvested from proestrus female and male rats in vitro. IL-6 significantly suppressed LHRH stimulated LH release from male dispersed pituitaries throughout the dose range, but did not influence basal LH release. IL-6 had no effect on basal or LHRH stimulated LH release in dispersed pituitaries from proestrus females. By contrast, TNF-alpha significantly suppressed LHRH stimulated LH release in dispersed pituitaries from proestrus female rats in a dose responsive manner, but did not influence basal LH release. TNF-alpha had no effect on basal or LHRH stimulated LH release in dispersed pituitaries from male rats. TNF-alpha and IL-6 had no effect on LHRH release from male hypothalamic explants in vitro. TNF-alpha and IL-6 had no effect on LHRH release from proestrus female hypothalamic explants in vitro. TNF-alpha and IL-6 have differential effects in dispersed pituitaries harvested from males and proestrus female rats. TNF-alpha and IL-6 may be important in mediating some of the nutritional effects on the reproductive Axis by acting at the level of the anterior pituitary rather than the hypothalamus.

  • Pyroglutamylated RFamide peptide 43 stimulates the Hypothalamic-Pituitary-Gonadal Axis via gonadotropin-releasing hormone in rats.
    Endocrinology, 2008
    Co-Authors: Sejal R Patel, Mohammad A. Ghatei, Emily L Thompson, Kevin G Murphy, Michael Patterson, Annette E. Curtis, Stephen R. Bloom
    Abstract:

    Although it is established that other members of the RFamide family stimulate the Hypothalamic-Pituitary-Gonadal Axis, the influence of the novel pyroglutamylated RFamide peptide 43 (QRFP43) is not known. We show intracerebroventricular (icv) administration of QRFP43 (2 nmol) to male rats increased plasma LH and FSH levels at 40 min after injection. icv administration of 3 nmol QRFP43 did not affect food intake in ad-libitum-fed male rats. The icv administration of 2 nmol QRFP43 did not significantly influence behavior in male rats. Intraperitoneal administration of doses up to 1200 nmol/kg QRFP43 in male rats did not significantly influence circulating gonadotropin or sex steroid levels. In vitro, QRFP43 stimulated GnRH release from hypothalamic explants from male rats and from GT1-7 cells. Pretreatment with a GnRH receptor antagonist, cetrorelix, blocked the increase in plasma LH levels after icv administration of QRFP43 (2 nmol). These results suggest that icv QRFP43 activates the hypothalamic-pituitar...

  • kisspeptin 54 stimulates the hypothalamic pituitary gonadal Axis in human males
    The Journal of Clinical Endocrinology and Metabolism, 2005
    Co-Authors: Waljit S Dhillo, Emily L Thompson, Kevin G Murphy, Michael Patterson, Owais B. Chaudhri, Vian Amber, Michael K Badman, Barbara M Mcgowan, Sejal R Patel, Mohammad A. Ghatei
    Abstract:

    Context: Mutation of the G protein-coupled receptor 54 is associated with a failure of reproductive function. The endogenous neuropeptide agonist for G protein-coupled receptor 54, kisspeptin, potently stimulates the Hypothalamic-Pituitary-Gonadal Axis in rodents and primates. Objective: The present study was designed to determine the effects of elevating circulating kisspeptin levels on LH, FSH, and testosterone in male volunteers. Design: This was a double-blind, placebo-controlled, crossover study. Setting: This was a hospital-based study. Participants: Male volunteers (n = 6) were recruited. Interventions: Each volunteer received a 90-min iv infusion of kisspeptin-54 (4 pmol/kg·min) and a control infusion of saline (0.9%) in random order. Main Outcome Measure: Plasma LH, FSH, and testosterone concentrations were measured. Results: Kisspeptin-54 infusion significantly increased plasma LH, FSH, and testosterone concentrations compared with saline infusion (mean 90-min LH: kisspeptin, 10.8 ± 1.5 vs. sali...

  • central and peripheral administration of kisspeptin 10 stimulates the hypothalamic pituitary gonadal Axis
    Journal of Neuroendocrinology, 2004
    Co-Authors: Emily L Thompson, Mohammad A. Ghatei, Michael Patterson, J F Todd, K Murphy, Kirsty L Smith, Waljit S Dhillo, S R Bloom
    Abstract:

    Kisspeptin is the peptide product of the KiSS-1 gene and the endogenous agonist for the GPR54 receptor. Recent evidence suggests the kisspeptin/GPR54 system is a key regulator of the reproductive system. We examined the effect of intracerebroventricular (i.c.v.) and peripheral administration of the active kisspeptin fragment, kisspeptin-10, on circulating gonadotrophins and total testosterone levels in adult male rats. The effect of kisspeptin-10 in vitro on the release of hypothalamic peptides from hypothalamic explants and gonadotrophins from anterior pituitary fragments was also determined. The i.c.v. administration of kisspeptin-10 dose-dependently increased plasma luteinizing hormone (LH) and increased plasma follicle stimulating hormone (FSH) and total testosterone at 60 min postinjection. In a separate study investigating the time course of this response, i.c.v. administered kisspeptin-10 (3 nmol) significantly increased plasma LH at 10, 20 and 60 min, FSH at 60 min and total testosterone at 20 and 60 min postinjection. Kisspeptin-10 stimulated the release of luteinizing hormone-releasing hormone (LHRH) from in vitro hypothalamic explants. Peripheral administration of kisspeptin-10 increased plasma LH, FSH and total testosterone. However, doses of 100–1000 nM kisspeptin-10 did not influence LH or FSH release from pituitary fragments in vitro. Kisspeptin therefore potently stimulates the Hypothalamic-Pituitary-Gonadal Axis. These effects are likely to be mediated via the hypothalamic LHRH system.

John A Cidlowski - One of the best experts on this subject based on the ideXlab platform.

  • a role for glucocorticoids in stress impaired reproduction beyond the hypothalamus and pituitary
    Endocrinology, 2013
    Co-Authors: Shannon Whirledge, John A Cidlowski
    Abstract:

    In addition to the well-characterized role of the sex steroid receptors in regulating fertility and reproduction, reproductive events are also mediated by the hypothalamic-pituitary-adrenal Axis in response to an individual's environment. Glucocorticoid secretion in response to stress contributes to the well-characterized suppression of the Hypothalamic-Pituitary-Gonadal Axis through central actions in the hypothalamus and pituitary. However, both animal and in vitro studies indicate that other components of the reproductive system are also regulated by glucocorticoids. Furthermore, in the absence of stress, it appears that homeostatic glucocorticoid signaling plays a significant role in reproduction and fertility in all tissues comprising the Hypothalamic-Pituitary-Gonadal Axis. Indeed, as central regulators of the immune response, glucocorticoids are uniquely poised to integrate an individual's infectious, inflammatory, stress, nutritional, and metabolic status through glucocorticoid receptor signaling in target tissues. Endocrine signaling between tissues regulating the immune and stress response and those determining reproductive status provides an evolutionary advantage, facilitating the trade-off between reproductive investment and offspring fitness. This review focuses on the actions of glucocorticoids in tissues important for fertility and reproduction, highlighting recent studies that show glucocorticoid signaling plays a significant role throughout the Hypothalamic-Pituitary-Gonadal Axis and characterizing these effects as permissive or inhibitory in terms of facilitating reproductive success.

Larry Lipshultz - One of the best experts on this subject based on the ideXlab platform.

  • Testosterone and male infertility
    Clinical Urologic Endocrinology: Principles for Men's Health, 2013
    Co-Authors: Tung Chin Hsieh, Matthew Mcintyre, Larry Lipshultz
    Abstract:

    Hypogonadism and its therapies have a significant impact on male fertility potential. It is necessary to determine the etiology to treat and counsel the patient appropriately on therapeutic options. For the hypogonadal male on exogenous testosterone, management should begin with cessation of the exogenous testosterone and supplemental subcutaneous human chorionic gonadotropin and an oral follicle-stimulating hormone (FSH)-inducing agent to allow reestablishment of the Hypothalamic-Pituitary-Gonadal Axis and spermatogenesis. Further supplemental therapy with recombinant FSH in some patients may be necessary to achieve optimal semen parameters.

Emily L Thompson - One of the best experts on this subject based on the ideXlab platform.

  • Pyroglutamylated RFamide peptide 43 stimulates the Hypothalamic-Pituitary-Gonadal Axis via gonadotropin-releasing hormone in rats.
    Endocrinology, 2008
    Co-Authors: Sejal R Patel, Mohammad A. Ghatei, Emily L Thompson, Kevin G Murphy, Michael Patterson, Annette E. Curtis, Stephen R. Bloom
    Abstract:

    Although it is established that other members of the RFamide family stimulate the Hypothalamic-Pituitary-Gonadal Axis, the influence of the novel pyroglutamylated RFamide peptide 43 (QRFP43) is not known. We show intracerebroventricular (icv) administration of QRFP43 (2 nmol) to male rats increased plasma LH and FSH levels at 40 min after injection. icv administration of 3 nmol QRFP43 did not affect food intake in ad-libitum-fed male rats. The icv administration of 2 nmol QRFP43 did not significantly influence behavior in male rats. Intraperitoneal administration of doses up to 1200 nmol/kg QRFP43 in male rats did not significantly influence circulating gonadotropin or sex steroid levels. In vitro, QRFP43 stimulated GnRH release from hypothalamic explants from male rats and from GT1-7 cells. Pretreatment with a GnRH receptor antagonist, cetrorelix, blocked the increase in plasma LH levels after icv administration of QRFP43 (2 nmol). These results suggest that icv QRFP43 activates the hypothalamic-pituitar...

  • kisspeptin 54 stimulates the hypothalamic pituitary gonadal Axis in human males
    Obstetrical & Gynecological Survey, 2007
    Co-Authors: Waljit S Dhillo, Emily L Thompson, Kevin G Murphy, Michael Patterson, Owais B. Chaudhri, Vian Amber, Michael K Badman, Barbara M Mcgowan, Sejal R Patel
    Abstract:

    Kisspeptin is a 54-amino acid peptide that activates the G protein-coupled receptor GPR54. This system appears to be an important regulator of reproduction. Mutation of GPR54 is associated with failed reproductive function. Studies in rodents and primates indicate that the endogenous neuropeptide agonist for GPR54, kisspeptin, strongly stimulates the Hypothalamic-Pituitary-Gonadal Axis. This double-blind, placebo-controlled, crossover study examined the effects of elevated circulating levels of kisspeptin on testosterone and gonadotropin concentrations in six males who received 90-minute intravenous infusions of 4 pmol/kg/minute of kisspeptin-54 and physiological saline in random order. Increasing infusion rates of kisspeptin-54 led to a dose-dependent rise in mean plasma kisspeptin immunoreactivity (IR). A dose-dependent increase in luteinizing hormone (LH) levels also was documented. Mean levels of follicle-stimulating hormone (FSH) also increased over time as kisspeptin-54 was infused, and there was a trend toward increased plasma testosterone levels. The increases in FSH and testosterone, however, were not dose-dependent. Elevations in circulating levels of LH, FSH, and testosterone were significant compared with responses to saline infusion. Infusion of kisspeptin-54 had no effect on the release of inhibin B or on sexual arousal scores. The course of kisspeptin-IR after reaching a plateau level followed first-order kinetics with a plasma half-life of 27 minutes, a mean metabolic clearance rate of 3.2 m/kg/minute, and a volume of distribution of 128 ml/kg. Systemic administration of kisspeptin-54 acutely increases circulating levels of gonadotropins and testosterone in human males. This potentially provides a novel means of manipulating the Hypothalamic-Pituitary-Gonadal Axis in patients with reproductive disorders.

  • kisspeptin 54 stimulates the hypothalamic pituitary gonadal Axis in human males
    The Journal of Clinical Endocrinology and Metabolism, 2005
    Co-Authors: Waljit S Dhillo, Emily L Thompson, Kevin G Murphy, Michael Patterson, Owais B. Chaudhri, Vian Amber, Michael K Badman, Barbara M Mcgowan, Sejal R Patel, Mohammad A. Ghatei
    Abstract:

    Context: Mutation of the G protein-coupled receptor 54 is associated with a failure of reproductive function. The endogenous neuropeptide agonist for G protein-coupled receptor 54, kisspeptin, potently stimulates the Hypothalamic-Pituitary-Gonadal Axis in rodents and primates. Objective: The present study was designed to determine the effects of elevating circulating kisspeptin levels on LH, FSH, and testosterone in male volunteers. Design: This was a double-blind, placebo-controlled, crossover study. Setting: This was a hospital-based study. Participants: Male volunteers (n = 6) were recruited. Interventions: Each volunteer received a 90-min iv infusion of kisspeptin-54 (4 pmol/kg·min) and a control infusion of saline (0.9%) in random order. Main Outcome Measure: Plasma LH, FSH, and testosterone concentrations were measured. Results: Kisspeptin-54 infusion significantly increased plasma LH, FSH, and testosterone concentrations compared with saline infusion (mean 90-min LH: kisspeptin, 10.8 ± 1.5 vs. sali...

  • central and peripheral administration of kisspeptin 10 stimulates the hypothalamic pituitary gonadal Axis
    Journal of Neuroendocrinology, 2004
    Co-Authors: Emily L Thompson, Mohammad A. Ghatei, Michael Patterson, J F Todd, K Murphy, Kirsty L Smith, Waljit S Dhillo, S R Bloom
    Abstract:

    Kisspeptin is the peptide product of the KiSS-1 gene and the endogenous agonist for the GPR54 receptor. Recent evidence suggests the kisspeptin/GPR54 system is a key regulator of the reproductive system. We examined the effect of intracerebroventricular (i.c.v.) and peripheral administration of the active kisspeptin fragment, kisspeptin-10, on circulating gonadotrophins and total testosterone levels in adult male rats. The effect of kisspeptin-10 in vitro on the release of hypothalamic peptides from hypothalamic explants and gonadotrophins from anterior pituitary fragments was also determined. The i.c.v. administration of kisspeptin-10 dose-dependently increased plasma luteinizing hormone (LH) and increased plasma follicle stimulating hormone (FSH) and total testosterone at 60 min postinjection. In a separate study investigating the time course of this response, i.c.v. administered kisspeptin-10 (3 nmol) significantly increased plasma LH at 10, 20 and 60 min, FSH at 60 min and total testosterone at 20 and 60 min postinjection. Kisspeptin-10 stimulated the release of luteinizing hormone-releasing hormone (LHRH) from in vitro hypothalamic explants. Peripheral administration of kisspeptin-10 increased plasma LH, FSH and total testosterone. However, doses of 100–1000 nM kisspeptin-10 did not influence LH or FSH release from pituitary fragments in vitro. Kisspeptin therefore potently stimulates the Hypothalamic-Pituitary-Gonadal Axis. These effects are likely to be mediated via the hypothalamic LHRH system.