Kisspeptin-GPR54 signaling is essential for preovulatory gonadotropin-releasing hormone neuron activation and the luteinizing hormone surge.

نویسندگان

  • Jenny Clarkson
  • Xavier d'Anglemont de Tassigny
  • Adriana Santos Moreno
  • William H Colledge
  • Allan E Herbison
چکیده

Kisspeptin and its receptor GPR54 have recently been identified as key signaling partners in the neural control of fertility in animal models and humans. The gonadotropin-releasing hormone (GnRH) neurons represent the final output neurons of the neural network controlling fertility and are suspected to be the primary locus of kisspeptin-GPR54 signaling. Using mouse models, the present study addressed whether kisspeptin and GPR54 have a key role in the activation of GnRH neurons to generate the luteinizing hormone (LH) surge responsible for ovulation. Dual-label immunocytochemistry experiments showed that 40-60% of kisspeptin neurons in the rostral periventricular area of the third ventricle (RP3V) expressed estrogen receptor alpha and progesterone receptors. Using an ovariectomized, gonadal steroid-replacement regimen, which reliably generates an LH surge, approximately 30% of RP3V kisspeptin neurons were found to express c-FOS in surging mice compared with 0% in nonsurging controls. A strong correlation was found between the percentage of c-FOS-positive kisspeptin neurons and the percentage of c-FOS-positive GnRH neurons. To evaluate whether kisspeptin and/or GPR54 were essential for GnRH neuron activation and the LH surge, Gpr54- and Kiss1-null mice were examined. Whereas wild-type littermates all exhibited LH surges and c-FOS in approximately 50% of their GnRH neurons, none of the mutant mice from either line showed an LH surge or any GnRH neurons with c-FOS. These observations provide the first evidence that kisspeptin-GPR54 signaling is essential for GnRH neuron activation that initiates ovulation. This broadens considerably the potential roles and therapeutic possibilities for kisspeptin and GPR54 in fertility regulation.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Minireview: kisspeptin neurons as central processors in the regulation of gonadotropin-releasing hormone secretion.

The Kiss1 gene encodes a family of peptides called kisspeptins, which bind to the G protein-coupled receptor GPR54. Kisspeptin(s) and its receptor are expressed in the forebrain, and the discovery that mice and humans lacking a functional GPR54 fail to undergo puberty and exhibit hypogonadotropic hypogonadism implies that kisspeptin signaling plays an essential role in reproduction. Studies in ...

متن کامل

Kisspeptin-gpr54 signaling at the GnRH neuron is necessary for negative feedback regulation of luteinizing hormone secretion in female mice.

Kisspeptin-Gpr54 signaling is critical for regulating the activity of gonadotropin-releasing hormone (GnRH) neurons in mammals. Previous studies have shown that the negative feedback mechanism is disrupted in global Gpr54-null mutants. The present investigation aimed to determine (1) if a lack of cyclical estrogen exposure of the GnRH neuronal network in the life-long hypogonadotropic Gpr54-nul...

متن کامل

Hypothalamic KiSS1/GPR54 Gene Expressions and Luteinizing Hormone Plasma Secretion in Morphine Treated Male Rats

Objective The inhibitory effects of Morphine and the stimulatory influence of kisspeptin signaling have been demonstrated on GnRH/LH release. Hypothalamic kisspeptin is involved in relaying the environmental and metabolic information to reproductive axis. In the present study the role of kisspeptin/GPR54 signaling system was investigated on relaying the inhibitory effects of morphine on LH horm...

متن کامل

Activation of gonadotropin-releasing hormone neurons by kisspeptin as a neuroendocrine switch for the onset of puberty.

We examined the role of kisspeptin and its receptor, the G-protein-coupled receptor GPR54, in governing the onset of puberty in the mouse. In the adult male and female mouse, kisspeptin (10-100 nM) evoked a remarkably potent, long-lasting depolarization of >90% of gonadotropin-releasing hormone (GnRH)-green fluorescent protein neurons in situ. In contrast, in juvenile [postnatal day 8 (P8) to P...

متن کامل

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

We have recently described a molecular gatekeeper of the hypothalamic-pituitary-gonadal axis with the observation that G protein-coupled receptor 54 (GPR54) is required in mice and men for the pubertal onset of pulsatile luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion to occur. In the present study, we investigate the possible central mode of action of GPR54 and kisspe...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • The Journal of neuroscience : the official journal of the Society for Neuroscience

دوره 28 35  شماره 

صفحات  -

تاریخ انتشار 2008