Kisspeptin directly stimulates gonadotropin-releasing hormone release via G protein-coupled receptor 54

Messager, Sophie; Chatzidaki, Emmanouella E.; Ma, Dan; Hendrick, Alan G.; Zahn, Dirk; Dixon, John; Thresher, Rosemary R.; Malinge, Isabelle; Lomet, Didier; Carlton, Mark; Colledge, William H; Caraty, Alain; Aparicio, Samuel

doi:10.1073/pnas.0409330102

Cited by 1,095 publications

(858 citation statements)

References 32 publications

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“…Additionally, the GnRH receptor antagonist, acyline, blocks gonadotropin release elicited by kisspeptin (Gottsch et al, 2004;Irwig et al, 2004;Shahab et al, 2005). A large proportion of GnRH cells co-express GPR54 mRNA, further supporting a direct mode of action by kisspeptin on GnRH neurons (Han et al, 2005;Irwig et al, 2004;Messager et al, 2005).…”

Section: Introductionmentioning

confidence: 85%

Suppression of kisspeptin expression and gonadotropic axis sensitivity following exposure to inhibitory day lengths in female Siberian hamsters

Mason

Greives

Scotti

et al. 2007

Hormones and Behavior

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To avoid breeding during unsuitable environmental or physiological circumstances, the reproductive axis adjusts its output in response to fluctuating internal and external conditions. The ability of the reproductive system to alter its activity appropriately in response to these cues has been well established. However, the means by which reproductively relevant cues are interpreted, integrated, and relayed to the reproductive axis remain less well specified. The neuropeptide kisspeptin has been shown to be a potent positive stimulator of the hypothalamo-pituitary-gonadal (HPG) axis, suggesting a possible neural locus for the interpretation/integration of these cues. Because a failure to inhibit reproduction during winter would be maladaptive for short-lived female rodents, female Siberian hamsters (Phodopus sungorus) housed in long and short days hamsters were examined. In long, 'summer' photoperiods, kisspeptin is highly expressed in the anteroventral periventricular nucleus (AVPV), with low expression in the arcuate nucleus (Arc). A striking reversal in this pattern is observed in animals held in short, 'winter' photoperiods, with negligible kisspeptin expression in the AVPV and marked staining in the Arc. Although all studies to date suggest that both populations act to stimulate the reproductive axis, these contrasting expression patterns of AVPV and Arc kisspeptin suggest disparate roles for these two cell populations. Additionally, we found that the stimulatory actions of exogenous kisspeptin are blocked by acyline, a gonadotropin-releasing hormone (GnRH) receptor antagonist, suggesting an action of kisspeptin on the GnRH system rather than pituitary gonadotropes. Finally, females held in short day lengths exhibit a reduced response to exogenous kisspeptin treatment relative to long-day animals. Together, these findings indicate a role for kisspeptin in the AVPV and Arc as an upstream integration center for reproductively-relevant stimuli and point to a dual mechanism of reproductive inhibition in which kisspeptin expression is reduced concomitant with reduced sensitivity of the HPG axis to this peptide.

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Section: Introductionmentioning

confidence: 85%

Suppression of kisspeptin expression and gonadotropic axis sensitivity following exposure to inhibitory day lengths in female Siberian hamsters

Mason

Greives

Scotti

et al. 2007

Hormones and Behavior

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“…In female sheep, it has been shown to stimulate GnRH and FSH secretion, to respond to sex steroids, and to play a role in the seasonality of ovulation (Messager et al, 2005;Smith et al, 2007 and2008). Importantly, in male rats, the kisspeptin receptor is found in over 75% of GnRH neurons (Irwig et al, 2004).…”

Section: Dimension 3 -The Communication Dimensionmentioning

confidence: 99%

Interactions between nutrition and reproduction in the management of the mature male ruminant

Martin¹,

Blache²,

Miller³

et al. 2010

Animal

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In mature male sheep and goats, changes in feed intake seem to have little effect on gonadal endocrine function but induce profound changes on sperm production. These outcomes are due to changes in size of the seminiferous tubules and in spermatogenic efficiency. Except with severe underfeeding, there are only minor changes in the endocrine function of the testis (testosterone production) unless season-long treatments are imposed. For cattle, nutrition clearly affects testicular development and the production of spermatozoa in young bulls, as it does in other species but, after the period of rapid growth has ended, there appears to be little or no response to nutrition. We are developing a clear picture of the metabolic signals, neuroendocrine processes and hormonal control systems that are involved, particularly for the mature male sheep. The energetic components of the diet, rather than protein, seem to be responsible, so we have envisaged a model of the relationship between energy balance and reproduction that has 4 'dimensions': genotype, structure (organs), communication (chemical and neural signals, nutrient sensing) and time (dynamics, metabolic memory, programming). We have linked these perspectives to 'resource allocation theory' and incorporated them into strategies for 'clean, green and ethical animal production'. In contrast to the clear outcomes with respect to spermatogenesis, the effects of nutrition on sexual behaviour are more difficult to define, perhaps because the behaviour is affected by a complex mix of physiological factors and because of flawed methods for quantifying male behaviour. For example, sexual behaviour is compromised by severe feed restriction, but male sexual behaviour requires intensive motor activity so a decline in libido could be caused by general weakness rather than specific nutritional limitations. The interaction between sexual activity and feeding behaviour also complicates the issue under field conditions. At the other end of the scale, overweight males can show reduced sexual success because they have difficulty courting and mounting. For this reason, exercise can enhance the fertilising capacity of rams. This will be important in extensive mating systems where males need to assemble and guard a harem and then mate many times for several weeks. For artificial insemination centres, there seems to be very few data on the nutritional management of males, but problems with overfed animals appear to be a risk. Future research should concentrate on the intra-testicular systems mediating the effects of nutrition on the production of spermatozoa.

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“…However, the action of GnRH on GnRH neurons or their neighboring cells has not been characterized in great depth, although several model cell lines, derived from mouse hypothalamic GnRH neurons, have provided the foundations for further functional studies [84,119]. More recently, the role of the metastin/kisspeptin receptor (gpr54) in influencing GnRH neuron function has been elucidated [30,85,117,138], but how mammalian GnRH I and GnRH II and the type I or type II GnRH receptors integrate into the complexity of neuronal function, in both males and females, still requires further elaboration.…”

Section: Potential Functions Of Gnrh In Mammalsmentioning

confidence: 99%

Diversity of actions of GnRHs mediated by ligand-induced selective signaling

Millar

Pawson

Morgan

et al. 2008

Frontiers in Neuroendocrinology

123

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Geoffrey Wingfield Harris' demonstration of hypothalamic hormones regulating pituitary function led to their structural identification and therapeutic utilization in a wide spectrum of diseases. Amongst these, Gonadotropin Releasing Hormone (GnRH) and its analogs are widely employed in modulating gonadotropin and sex steroid secretion to treat infertility, precocious puberty and many hormone-dependent diseases including endometriosis, uterine fibroids and prostatic cancer. While these effects are all mediated via modulation of the pituitary gonadotrope GnRH receptor and the G q signaling pathway, it has become increasingly apparent that GnRH regulates many extrapituitary cells in the nervous system and periphery. This review focuses on two such examples, namely GnRH analog effects on reproductive behaviors and GnRH analog effects on the inhibition of cancer cell growth. For both effects the relative activities of a range of GnRH analogs is distinctly different from their effects on the pituitary gonadotrope and different signaling pathways are utilized. As there is only a single functional GnRH receptor type in man we have proposed that the GnRH receptor can assume different conformations which have different selectivity for GnRH analogs and intracellular signaling proteins complexes. This ligand-induced selective-signaling recruits certain pathways while by-passing others and has implications in developing more selective GnRH analogs for highly specific therapeutic intervention.

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Kisspeptin directly stimulates gonadotropin-releasing hormone release via G protein-coupled receptor 54

Cited by 1,095 publications

References 32 publications

Suppression of kisspeptin expression and gonadotropic axis sensitivity following exposure to inhibitory day lengths in female Siberian hamsters

Suppression of kisspeptin expression and gonadotropic axis sensitivity following exposure to inhibitory day lengths in female Siberian hamsters

Interactions between nutrition and reproduction in the management of the mature male ruminant

Diversity of actions of GnRHs mediated by ligand-induced selective signaling

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