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1 1522 Exp Physiol (2013) pp Symposium Report Use of genetic models of idiopathic hypogonadotrophic hypogonadism in mice and men to understand the mechanisms of disease Margaret F. Lippincott,CadenceTrue and Stephanie B. Seminara Harvard Reproductive Sciences Center and Reproductive Endocrine Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA Experimental Physiology New findings What is the topic of this review? This review discusses the genetics of idiopathic hypogonadotrophic hypogonadism, with a focus on how deficiencies in the kisspeptin and neurokinin B pathways result in reproductive dysfunction in both mice and men. What advances does it highlight? In humans, deficiencies in kisspeptin signalling lead to a sustained absence of puberty. Mutations in the neurokinin B pathway are also associated with an initial absence of pubertal development, but the hypogonadotrophism can improve later in life with spontaneous activation of the hypothalamic pituitary gonadal cascade. Mouse models with mutations in each of these pathways recapitulate many of the features observed in human patients. Spontaneous recovery of gonadotrophin-releasing hormone secretion, termed reversal, indicates that the hypothalamic pituitary gonadal axis may be capable of awakening in the setting of neurokinin B signalling abnormalities. Mutations in the genes encoding the neuropeptides kisspeptin and neurokinin B, as well as their receptors, are associated with gonadotrophin-releasing hormone(gnrh) deficiency and a failure to initiate and/or progress through puberty. Although the total number of patients studied to date is small, mutations in the kisspeptin pathway appear to result in lifelong GnRH deficiency. Mice with mutations in kisspeptin and the kisspeptin receptor, Kiss1 / and Kiss1r /, respectively, appear to be phenocopies of the human with abnormal sexual maturation and infertility. In contrast, mutations in the neurokinin B pathway lead to a more variable adult reproductive phenotype, with a subset of hypogonadotrophic individuals demonstrating paradoxical recovery of reproductive function later in life. While reversal remains poorly understood, the ability to recover reproductive function indicates that neurokinin B may play different roles in the initiation of sexual maturation compared with the maintenance of adult reproductive function. Mice with mutations in the gene encoding the neurokinin B receptor, Tacr3, have abnormal oestrous cycles and subfertility but, similar to their human counterparts, appear less severely affected than mice with kisspeptin deficiency. Further investigations into the interaction between the kisspeptin and neurokinin B pathways will reveal key insights into how GnRH neuronal modulation occurs at puberty and throughout reproductive life. M. F. Lippincott and C. True contributed equally to the manuscript. DOI: /expphysiol
2 Exp Physiol (2013) pp Kisspeptin and neurokinin B deficiencies in mice and men 1523 (Received 24 May 2013; accepted after revision 16 August 2013; first published online 16 August 2013) Corresponding author S. B. Seminara: Harvard Reproductive Sciences Center and Reproductive Endocrine Unit, Department of Medicine, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA. sseminara@ partners.org Introduction Pulsatile secretion of gonadotrophin-releasing hormone (GnRH) from the hypothalamus stimulates release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary, which in turn stimulate the production of sex steroids, spermatogenesis and follicle development. The hypothalamic pituitary gonadal axis is activated initially during neonatal life, becomes quiescent during childhood and then re-awakens during sexual maturation. Idiopathic hypogonadotrophic hypogonadism (IHH) is a condition characterized by an abnormal pattern of GnRH secretion or action that results in low levels of gonadotrophins and, by extension, sex steroids. This disease entity has provided a unique biological opportunity to discover novel modulators of GnRH secretion. Over the last 20 years, genetic studies of IHH patients have led to the discovery of several pathways affecting GnRH neuronal migration as well as GnRH secretion/action (Balasubramanian et al. 2010). In the latter category, mutations in the genes encoding kisspeptin, neurokinin B (NKB) and their respective receptors have all been identified in patients with IHH (de Roux et al. 2003; Seminara et al. 2003; Topaloglu et al. 2009, 2012). These two neuropeptides, in addition to a third peptide hormone, dynorphin, are coexpressed within a particular neuronal population of the hypothalamus (KNDy neurons) and appear to be critical components of the hypothalamic circuitry regulating GnRH release. While kisspeptin and NKB regulate GnRH release, deficiencies in these systems lead to distinct phenotypes of hypogonadotrophic hypogonadism in both human and animal models and suggest differing roles for these neuropeptides in the regulation of sexual maturation. Kisspeptin, NKB and KNDy neuronal physiology Exogenous kisspeptin administration potently stimulates GnRH-induced LH release in mice, rats, primates, sheep and humans (Smith et al. 2006). Kisspeptin expression increases throughout sexual maturation in mice (Han et al. 2005), rats (Navarro et al. 2004a) and monkeys (Shahab et al. 2005), and exogenous kisspeptin administration can advance the onset of sexual maturation in rats (Navarro et al. 2004b). In electrophysiological recordings, kisspeptin stimulates GnRH neuronal firing (Han et al. 2005). In addition, GnRH responsiveness to kisspeptin appears to increase throughout sexual development; a response that can be modulated by steroid hormones (Roa et al. 2006; Guerriero et al. 2012). This apparent regulatory relationship between kisspeptin and circulating hormones (i.e. estradiol) may be affected by the process of sexual maturation itself (Guerriero et al. 2012). Similar to kisspeptin, NKB levels increase in the hypothalamus at the time of sexual maturation (Navarro et al. 2012), and antagonism of the NKB receptor delays the onset of puberty (Navarro et al. 2012). While sex steroids may modulate the magnitude of the GnRH response to kisspeptin, they appear to modulate the directionality of the GnRH response to NKB (Navarro 2012). In general, senktide (an NKB receptor agonist) inhibits GnRH release in castrated animals, but stimulates GnRH release in animals with physiological levels of sex steroids (Navarro et al. 2011b). However, numerous exceptions to this rule have been observed, indicating that factors apart from steroids are also likely to influence the effect of senktide upon LH secretion (Sandoval-Guzmán & Rance, 2004; Wakabayashi et al. 2010; Kinsey-Jones et al. 2012). The effects of NKB receptor activation appear to differ according to species, because senktide stimulates LH in intactadultmalemicebuthasnoeffectinintactadult male rats (Navarro et al. 2011b; Ruiz-Pino et al. 2012). Pubertal development also appears to regulate the effects of NKB on LH release, because prepubertal animals have a uniformly positive response to senktide, in contrast to the more diverse responses observed in adults. Senktide adminstration has also been shown to elicit a biphasic LH response, comprising stimulation followed by inhibition (Wakabayashi et al. 2010; Grachev et al. 2012a), in several species. Despite initial stimulation, repeated boluses of NKB fail to bring about an LH response, indicating that there may also be rapid desensitization of the NKB response (Ramaswamy et al. 2010). Thus, in comparison to kisspeptin, the neuroendocrine response to senktide is more complex and nuanced, suggesting, by extension, greater complexity in the role of NKB in modulating the hypothalamic pituitary gonadal cascade. In fact, several studies suggest that the NKB signalling pathway sits physiologically upstream of kisspeptin. The NKB receptor does not appear to be expressed in GnRH cell bodies, and NKB does not stimulate the electrical activity of GnRH neuronal cell bodies in recordings from mouse brain slices (Navarro et al. 2011b), leading to a prevailing hypothesis that the effects of NKB on GnRH release are indirect. In contrast to recordings from GnRH cells, KNDy neuronal firing does increase in response to NKB receptor activation, and roughly 95%
3 1524 M. F. Lippincott and others Exp Physiol (2013) pp of KNDy neurons express the NKB receptor (Navarro et al. 2011a). Both physiological desensitization (Ramaswamy et al. 2011) and pharmacological blockade (Grachev et al. 2012b) of the kisspeptin receptor appear to abrogate the effects NKB of on LH release, which is once again consistent with NKB signalling indirectly through kisspeptin. However, in contrast to the cell bodies, it appears that GnRH fibre terminals do express the NKB receptor, and thus it remains possible that NKB could still directly regulate GnRH release at this site (Krajewski et al. 2005). While it remains unclear what, if any, direct effects NKB has upon GnRH cells, evidence from humans and mice bearing deleterious mutations within the kisspeptin and NKB signalling pathways supports the physiological model of NKB signalling predominantly through kisspeptin, which in turn directly regulates GnRH (Fig. 1). Genotype/phenotype of kisspeptin and NKB pathway mutations implicated in IHH Kisspeptin was initially implicated in the onset of puberty after two research groups independently discovered mutations in KISS1R, the gene encoding the kisspeptin receptor, in patients with IHH (de Roux et al. 2003; Seminara et al. 2003). Sincetheseinitialstudies, additional Figure 1. Kisspeptin and neurokinin B (NKB) pathway deficiencies and resulting phenotypes in mice and men Neurokinin B is hypothesized to regulate kisspeptin (Kiss1) release, which in turn stimulates gonadotrophin-releasing hormone (GnRH) release and normal reproductive function (left panel). It remains unclear at this time whether NKB might also directly regulate GnRH release (dashed line). Neurokinin B pathway deficiency (middle panel) is hypothesized to cause a decrease in Kiss1 and subsequently GnRH release, resulting in idiopathic hypogonadotrophic hypogonadism (IHH), with a subset of patients reversing later in life; NKB pathway-deficient mice are subfertile. In contrast, Kiss1 pathway deficiencies appear to result in a more dramatic decrease in GnRH release, causing life-long IHH in humans and complete infertility in mice. mutations in KISS1R resulting in decreased or loss of receptor function have been found in approximately 10 families (Breuer et al. 2012; Brioude et al. 2013). Heterozygous (Chan et al. 2011) and homozygous deleterious mutations (Topaloglu et al. 2012) have also been identified in KISS1 in patients with IHH. In contrast to these loss-of-function mutations, gain-of-function mutations in KISS1R (resulting in prolonged signalling; Teles et al. 2008) and in KISS1 (resulting in increased peptide stability; Silveira et al. 2010a) have both been implicated in central precocious puberty. Thus, both naturally occurring loss-of-function and gain-of-function mutations indicate the importance of the kisspeptin signalling pathway in modulating the timing of pubertal onset in humans (Fig. 1). The phenotypes of patients carrying disabling mutations in KISS1R are severe, with hypogonadotrophism accompanied by microphallus and cryptorchidism in some cases. However, evidence from clinical histories (de Roux et al. 2003; Tenenbaum-Rakover et al. 2007), laboratory examinations (de Roux et al. 2003; Tenenbaum-Rakover et al. 2007) and neuroendocrine studies (Seminara et al. 2003; Tenenbaum-Rakover et al. 2007) suggests that endogenous GnRH secretion, albeit enfeebled, can exist in the face of loss-of-function kisspeptin receptor mutations. Although far fewer patients have been identified with bialellic mutations in KISS1,the only family reported to date with a homozygous mutation also appears to have a severe phenotype (Topaloglu et al. 2012). Like kisspeptin, the NKB pathway has been implicated in the regulation of GnRH release by the discovery of mutations in the genes encoding NKB (TAC3) and its receptor(tacr3) in IHH patients (Topaloglu et al. 2009). Mutations in the NKB signalling pathway are more common than those in the kisspeptin pathway, with mutations in the former accounting for roughly 5% of all IHH cases (Gianetti et al. 2010). The majority of individuals carrying NKB pathway mutations have a phenotype of IHH similar to kisspeptin pathway disruptions (Silveira et al. 2010b; Francouet al. 2011); however, some subjects demonstrate partial pubertal development (Fukami et al. 2010; Gianetti et al. 2010). As with kisspeptin pathway mutations, both homozygous and heterozygous mutations in NKB signalling genes have been implicated in IHH (Gianetti et al. 2010). Evolution of genotype/phenotype of kisspeptin and NKB pathway mutations: reversal While the initial presentation of patients bearing deleterious genetic variants in the kisspeptin and NKB pathways is similar, the phenotype diverges in adulthood. Although hypogonadotrophism appears to be sustained in KISS1/KISS1R-deficient individuals, hypogonadotrophism may not be permanent in patients
4 Exp Physiol (2013) pp Kisspeptin and neurokinin B deficiencies in mice and men 1525 with TAC3/TACR3 pathway mutations. The majority of IHH patients bearing disabling mutations in the NKB pathway (assessed long term) exhibit evidence of spontaneous partial or complete recovery of their reproductive axis as determined by the following changes: (i) increases in LH pulsatility; (ii) increases in testosterone; (iii) increases in testicular volume; (iv) the presence of withdrawal bleeding; (v) spontaneous menstrual cycles; and/or (vi) spontaneous pregnancy (Gianetti et al. 2010). The observed rate of reversal in IHH patients with NKB pathway mutations and long term follow-up is estimated to be 80% (Gianetti et al. 2010); however, the rate of reversal is much lower, 10%, in a diverse IHH population unselected for genotype (Raivio et al. 2007). While mutations in KISS1 and KISS1R are rarer than those in TAC3/TACR3, to date, no individuals with kisspeptin pathway mutations have been documented with reversal. Thus, the role of the NKB pathway in GnRH secretion may be less critical in adult life compared with that of kisspeptin. In fact, kisspeptin signalling may be able to overcome NKB pathway mutations as evidenced by an increase in LH pulsatility in patients with TAC3 or TACR3 mutations receiving exogenous pharmacological doses of kisspeptin (Young et al. 2012). Additionally, it is possible that in the absence of either NKB or its receptor there is compensation by other tachykinin ligands and/or receptors, as suggested by recent animal studies (see next section; Fig. 1). Genotype/phenotype of kisspeptin and NKB pathway mutations in mice Utilization of mouse models deficient in kisspeptin and NKB allows for a more in-depth probing of the mechanism by which these neuropeptides regulate the hypothalamic control of reproduction. Kiss1r / mice demonstrate a profound reproductive phenotype of absent sexual maturation and infertility (Funes et al. 2003; Seminara et al. 2003); a phenotype that is largely echoed in Kiss1 / mice (d Anglemont de Tassigny et al. 2007; Lapatto et al. 2007). However, both Kiss1 / and Kiss1r / mutant mice demonstrate kisspeptin-independent GnRH release as evidenced by measurable gonadotrophin levels (Chan et al. 2009), harkening back to the enfeebled GnRH secretion observed in human patients bearing mutationsinthispathway.inthenkbpathway,tacr3 / mice were reported initially to be fertile, leading to a puzzling discordance between mouse and human geneticmodels(kunget al. 2004). However, upon more detailed phenotyping, Tacr3 / mice were found to have reproductive defects, including impaired oestrous cyclicity, decreased ovulatory events and subfertility (Yang et al. 2012). Although not perfect phenocopies of each other, humans and mice demonstrate that disabling mutations in the NKB pathway give rise to phenotypes that are more similar than previously appreciated. Similar to phenotypes in humans with NKB signalling deficiency, Tacr3 / mice have less profound adult reproductive deficits compared with Kiss1 / and Kiss1r / mice (Fig. 1). There is mounting evidence in the mouse that NKB may be capable of signalling through the other two tachykinin receptors, NK1R and NK2R, to activate KNDy neurons (de Croft et al. 2013). Neurokinin B might signal through these other tachykinin receptors in Tacr3 / mice to regulate reproductive function and produce only a subfertility phenotype. The KNDy neurons also appear to be activated by the other two tachykinin ligands, substance P and neurokinin A, hinting at a much more complicated role for the tachykinin system in the regulation of GnRH release than previously appreciated. This potential redundancy of NKB could be yet another layer of complexity that contributes to a more variable reproductive phenotype in NKB-deficient states compared with the straightforward infertility phenotypes in kisspeptin-deficient states. The interplay between human phenotypes and mouse modelling remains essential for dissecting the hypothalamic signalling pathway responsible for reproduction. Genetic and physiological investigations are consistent with the hypothesis that NKB is upstream of kisspeptin and regulates kisspeptin release, a role especially critical in the timing of puberty. Overall, deficiencies in the kisspeptin system appear to be more severe than those in the NKB system. The ability of NKB-deficient IHH individuals to undergo reversal of their hypogonadism suggests a plasticity and redundancy heretofore underappreciated in the hypothalamic control of puberty. Ongoing multidisciplinary work using both animal and human models will be particularly beneficial in continuing to uncover the hypothalamic pathways regulating reproductive function. References Balasubramanian R, Dwyer A, Seminara SB, Pitteloud N, Kaiser UB & Crowley WF Jr (2010). Human GnRH deficiency: a unique disease model to unravel the ontogeny of GnRH neurons. Neuroendocrinology 92, Breuer O, Abdulhadi-Atwan M, Zeligson S, Fridman H, Renbaum P, Levy-Lahad E & Zangen DH (2012). A novel severe N-terminal splice site KISS1R gene mutation causes hypogonadotropic hypogonadism but enables a normal development of neonatal external genitalia. Eur J Endocrinol 167, Brioude F, Bouligand J, Francou B, Fagart J, Roussel R, Viengchareun S, Combettes L, Brailly-Tabard S, Lombès M, Young J & Guiochon-Mantel A (2013). Two families with normosmic congenital hypogonadotropic hypogonadism and biallelic mutations in KISS1R (KISS1 receptor): clinical evaluation and molecular characterization of a novel mutation. PLoS One 8, e53896.
5 1526 M. F. Lippincott and others Exp Physiol (2013) pp Chan YM, Broder-Fingert S, Paraschos S, Lapatto R, Au M, Hughes V, Bianco SD, Min L, Plummer L, Cerrato F, De Guillebon A, Wu IH, Wahab F, Dwyer A, Kirsch S, Quniton R, Cheetham T, Ozata M, Ten S, Chanoine JP, Pitteloud N, Martin KA, Schiffmann R, Van der Kamp HJ, Nader S, Hall JE, Kaiser UB & Seminara SB (2011). GnRH-deficient phenotypes in humans and mice with heterozygous variants in KISS1/Kiss1. J Clin Endocrinol Metab 96, E1771 E1781. Chan YM, Broder-Fingert S, Wong KM & Seminara SB (2009). Kisspeptin/Gpr54-independent gonadotrophin-releasing hormoneactivityin Kiss1 and Gpr54 mutant mice. J Neuroendocrinol 21, d Anglemont de Tassigny X, Fagg LA, Dixon JP, Day K, Leitch HG, Hendrick AG, Zahn D, Franseschini I, Caraty A, Carlton MB, Aparicio SA & Colledge WH (2007). Hypogonadotropic hypogonadism in mice lacking a functional Kiss1 gene. Proc Natl Acad Sci U S A 104, de Croft S, Boehm U & Herbison AE (2013). Neurokinin B activates arcuate kisspeptin neurons through multiple tachykinin receptors in the male mouse. Endocrinology 154, de Roux N, Genin E, Carel JC, Matsuda F, Chaussain JL & Milgrom E (2003). Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. Proc Natl Acad Sci U S A 100, Francou B, Bouligand J, Voican A, Amazit L, Trabado S, Fagart J, Meduri G, Brailly-Tabard S, Chanson P, Lecompte P, Guiochon-Mantel S & Young J (2011). Normosmic congenital hypogonadotropic hypogonadism due to TAC3/TACR3 mutations: characterization of neuroendocrine phenotypes and novel mutations. PLoS One 6, e Fukami M, Maruyama T, Dateki S, Sato N, Yoshimura Y & Ogata T (2010). Hypothalamic dysfunction in a female with isolated hypogonadotropic hypogonadism and compound heterozygous TACR3 mutations and clinical manifestation in her heterozygous mother. Horm Res Paediatr 73, Funes S, Hedrick JA, Vassileva G, Markowitz L, Abbondanzo S, Golovko A, Yang S, Monsma FJ & Gustafson EL (2003). The KiSS-1 receptor GPR54 is essential for the development of the murine reproductive system. Biochem Biophys Res Commun 312, Gianetti E, Tusset C, Noel SD, Au MG, Dwyer AA, Hughes VA, Abreu AP, Carroll J, Trarbach E, Silveira LF, Costa EM, de Monçada BB, de Castro M, Lofrano A, Hall JE, Bolu E, Ozata M, Quinton R, Amory JK, Stewart SE, Arlt W, Cole TR, Crowley WF, Kaiser WB, Latronico AC & Seminara SB (2010). TAC3/TACR3 mutations reveal preferential activation of gonadotropin-releasing hormone release by neurokinin B in neonatal life followed by reversal in adulthood. J Clin Endocrinol Metab 95, Grachev P, Li XF, Kinsey-Jones JS, di Domenico AL, Millar RP, LightmanSL & O Byrne KT (2012a). Suppression of the GnRH pulse generator by neurokinin B involves a κ-opioid receptor-dependent mechanism. Endocrinology 153, Grachev P, Li XF, Lin YS, Hu MH, Elsamani L, Paterson SJ, Millar RP, Lightman SL & O Byrne KT (2012b). GPR54-dependent stimulation of luteinizing hormone secretion by neurokinin B in prepubertal rats. PLoS One 7, e Guerriero KA, Keen KL, Millar RP & Terasawa E (2012). Developmental changes in GnRH release in response to kisspeptin agonist and antagonist in female rhesus monkeys (Macaca mulatta): implication for the mechanism of puberty. Endocrinology 153, Han SK, Gottsch ML, Lee KJ, Popa SM, Smith JT, Jakawich SK, Clifton DK, Steiner RA & Herbison AE (2005). Activation of gonadotropin-releasing hormone neurons by kisspeptin as a neuroendocrine switch for the onset of puberty. JNeurosci 25, Kinsey-JonesJS,GrachevP,LiXF,LinYS,MilliganSR, Lightman SL & O Byrne KT (2012). The inhibitory effects of neurokinin B on GnRH pulse generator frequency in the female rat. Endocrinology 153, Krajewski SJ, Anderson MJ, Iles-Shih L, Chen KJ, Urbanski HF & Rance NE (2005). Morphologic evidence that neurokinin B modulates gonadotropin-releasing hormone secretion via neurokinin 3 receptors in the rat median eminence. JCompNeurol489, Kung TT, Crawley Y, Jones H, Luo B, Gilchrest H, Greenfeder S, Anthes JC, Lira S, Wiekowski M, Cook DN, Hey JA, Egan RW & Chapman RW (2004). Tachykinin NK 3 -receptor deficiency does not inhibit pulmonary eosinophilia in allergic mice. Pharmacol Res 50, Lapatto R, Pallais JC, Zhang D, Chan YM, Mahan A, Cerrato F, Le WW, Hoffman GE & Seminara SB (2007). Kiss1 / mice exhibit more variable hypogonadism than Gpr54 / mice. Endocrinology 148, NavarroM,GinebraMP,PlanellJA,ZeppetelliS&AmbrosioL (2004a). Development and cell response of a new biodegradable composite scaffold for guided bone regeneration. J Mater Sci Mater Med 15, Navarro VM (2012). New insights into the control of pulsatile GnRH release: the role of Kiss1/neurokinin B neurons. Front Endocrinol (Lausanne) 3, 48. Navarro VM, Castellano JM, McConkey SM, Pineda R, Ruiz-Pino F, Pinilla L, Clifton DK, Tena-Sempere M & Steiner RA (2011a). Interactions between kisspeptin and neurokinin B in the control of GnRH secretion in the female rat. Am J Physiol Endocrinol Metab 300, E202 E210. Navarro VM, Fernández-FernándezR, CastellanoJM, Roa J, Mayen A, Barreiro ML, Gaytan F, Aguilar E, Pinilla L, Dieguez C & Tena-Sempere M (2004b). Advanced vaginal opening and precocious activation of the reproductive axis by KiSS-1 peptide, the endogenous ligand of GPR54. J Physiol 561, Navarro VM, Gottsch ML, Wu M, García-Galiano D, Hobbs SJ, Bosch MA, Pinilla L, Clifton DK, Dearth A, Ronnekleiv OK, Braun RE, Palmiter RD, Tena-Sempere M, Alreja M & Steiner RA (2011b). Regulation of NKB pathways and their roles in the control of Kiss1 neurons in the arcuate nucleus of the male mouse. Endocrinology 152, Navarro VM, Ruiz-Pino F, Sánchez-Garrido MA, García-Galiano D, Hobbs SJ, Manfredi-Lozano M, León S, Sangiao-Alvarellos S, Castellano JM, Clifton DK, Pinilla L, Steiner RA & Tena-Sempere M (2012). Role of neurokinin B in the control of female puberty and its modulation by metabolic status. JNeurosci32,
6 Exp Physiol (2013) pp Kisspeptin and neurokinin B deficiencies in mice and men 1527 Raivio T, Falardeau J, Dwyer A, Quinton R, Hayes FJ, Hughes VA, Cole LW, Pearce SH, Lee H, Boepple P, Crowley WF Jr & Pitteloud N (2007). Reversal of idiopathic hypogonadotropic hypogonadism. NEnglJMed357, Ramaswamy S, Seminara SB, Ali B, Ciofi P, Amin NA & Plant TM (2010). Neurokinin B stimulates GnRH release in the male monkey (Macaca mulatta) and is colocalizedwith kisspeptin in the arcuate nucleus. Endocrinology 151, Ramaswamy S, Seminara SB & Plant TM (2011). Evidence from the agonadal juvenile male rhesus monkey (Macaca mulatta) for the view that the action of neurokinin B to trigger gonadotropin-releasing hormone release is upstream from the kisspeptin receptor. Neuroendocrinology 94, RoaJ,VigoE,CastellanoJM,NavarroVM, Fernández-Fernández R, Casanueva FF, Dieguez C, Aguilar E, Pinilla L & Tena-Sempere M (2006). Hypothalamic expression of KiSS-1 system and gonadotropin-releasing effects of kisspeptin in different reproductive states of the female rat. Endocrinology 147, Ruiz-Pino F, Navarro VM, Bentsen AH, Garcia-Galiano D, Sanchez-Garrido MA, Ciofi P, Steiner RA, Mikkelsen JD, Pinilla L & Tena-Sempere M (2012). Neurokinin B and the control of the gonadotropic axis in the rat: developmental changes, sexual dimorphism, and regulation by gonadal steroids. Endocrinology 153, Sandoval-Guzmán T & Rance NE (2004). Central injection of senktide, an NK 3 receptor agonist, or neuropeptide Y inhibits LH secretion and induces different patterns of Fos expression in the rat hypothalamus. Brain Res 1026, Seminara SB, Messager S, Chatzidaki EE, Thresher RR, Acierno JS Jr, Shagouri JK, Bo-Abbas Y, Kuohung W, Schwinhof KA, Hendrick AG, Zahn D, Dixon J, Kaiser UB, Slaugenhaupt SA, Gusella JF, O Rahilly S, Carlton MB, Crowley WF Jr, AparicioSA & ColledgeWH (2003). The GPR54 gene as a regulator of puberty. NEnglJMed349, Shahab M, Mastronardi C, Seminara SB, Crowley WF, Ojeda SR & Plant TM (2005). Increased hypothalamic GPR54 signaling: a potential mechanism for initiation of puberty in primates. Proc Natl Acad Sci U S A 102, Silveira LG, Noel SD, Silveira-Neto AP, Abreu AP, Brito VN, Santos MG, Bianco SD, Kuohung W, Xu S, Gryngarten M, Escobar ME, Arnhold IJ, Mendonca BB, Kaiser UB & Latronico AC (2010a). Mutationsof thekiss1 gene in disorders of puberty. J Clin Endocrinol Metab 95, SilveiraLG, Tusset C & LatronicoAC (2010b). Impact of mutations in kisspeptin and neurokinin B signaling pathways on human reproduction. Brain Res 1364, Smith JT, Clifton DK & Steiner RA (2006). Regulation of the neuroendocrine reproductive axis by kisspeptin-gpr54 signaling. Reproduction 131, Teles MG, Bianco SD, Brito VN, Trarbach EB, Kuohung W, Xu S, Seminara SB, Mendonca BB, Kaiser UB & Latronico AC (2008). A GPR54-activating mutation in a patient with central precocious puberty. NEnglJMed358, Tenenbaum-Rakover Y, Commenges-Ducos M, Iovane A, Aumas C, Admoni O & de Roux N (2007). Neuroendocrine phenotype analysis in five patients with isolated hypogonadotropic hypogonadism due to a L102P inactivating mutation of GPR54. J Clin Endocrinol Metab 92, Topaloglu AK, Reimann F, Guclu M, Yalin AS, Kotan LD, Porter KM, Serin A, Mungan NO, Cook JR, Ozbek MN, Imamoglu S, Akalin NS, Yuksel B, O Rahilly S & Semple RK (2009). TAC3 and TACR3 mutations in familial hypogonadotropic hypogonadism reveal a key role for Neurokinin B in the central control of reproduction. Nat Genet 41, Topaloglu AK, Tello JA, Kotan LD, Ozbek MN, Yilmaz MB, Erdogan S, Gurbuz F, Temiz F, Millar RP & Yuksel B (2012). Inactivating KISS1 mutation and hypogonadotropic hypogonadism. NEnglJMed366, Wakabayashi Y, Nakada T, Murata K, Ohkura S, Mogi K, Navarro VM, Clifton DK, Mori Y, Tsukamura H, Maeda K, Steiner RA & Okamura H (2010). Neurokinin B and dynorphin A in kisspeptin neurons of the arcuate nucleus participate in generation of periodic oscillation of neural activity driving pulsatile gonadotropin-releasing hormone secretion in the goat. JNeurosci30, Yang JJ, Caligioni CS, Chan YM & Seminara SB (2012). Uncovering novel reproductive defects in neurokinin B receptor null mice: closing the gap between mice and men. Endocrinology 153, Young J, George JT, Tello JA, Francou B, Bouligand J, Guiochon-Mantel A, Brailly-Tabard S, Anderson RA & Millar RP (2012). Kisspeptin restores pulsatile LH secretion in patients with neurokinin B signaling deficiencies: physiological, pathophysiological and therapeutic implications. Neuroendocrinology 97, Additional information Competing interests None declared. Funding This work was supported by National Institutes of Health grants U54 HD028138, ROI HD and K24 HD
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