Central injection of senktide, an NK3 receptor agonist, or neuropeptide Y inhibits LH secretion and induces different patterns of Fos expression in the rat hypothalamus

Sandoval-Guzmán, Tatiana; Rance, Naomi E.

doi:10.1016/j.brainres.2004.08.026

Cited by 149 publications

(130 citation statements)

References 38 publications

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“…Of note, the stimulatory effects of senktide on LH secretion were abrogated in Gpr54 null mice, thus suggesting that these require the integrity of kisspeptin signaling to manifest (35), a contention that is also supported by recent findings in the monkey (36). Notwithstanding these solid pharmacological data, evidence for null or even inhibitory responses to NKB agonists has also been presented (37,38). The basis for these discrepant observations remains partially unknown, but they may stem from differences in the age, sex, species, and prevailing gonadotropin levels.…”

Section: Kisspeptins: Major Gatekeepers Of Pubertymentioning

confidence: 76%

“…In this context, proof of desensitization of NKB-induced LH responses has been presented in the monkey (28). This desensitization might account for the null or even inhibitory effect of senktide on LH secretion in GNX rodents and ewes (25,33,34,37), as they are expected to have pre-elevated, endogenous levels of NKB. Anyhow, the hypogonadotropic phenotype of humans with inactivating mutations of the NKB pathway, together with the reported effects of NKB agonists on LH release under physiological conditions in different species, solidly document the predominant stimulatory role of NKB in the central control of the HPG axis.…”

Section: Kisspeptins: Major Gatekeepers Of Pubertymentioning

confidence: 93%

“…The basis for these discrepant observations remains partially unknown, but they may stem from differences in the age, sex, species, and prevailing gonadotropin levels. Indeed, evidence for inhibitory effects of senktide on LH secretion comes mostly from animal models with pre-elevated LH concentrations, namely gonadectomy (GNX) without adequate sex steroid replacement (37,38,39). In this context, proof of desensitization of NKB-induced LH responses has been presented in the monkey (28).…”

Section: Kisspeptins: Major Gatekeepers Of Pubertymentioning

confidence: 99%

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ENDOCRINOLOGY AND ADOLESCENCE: Deciphering puberty: novel partners, novel mechanisms

Tena‐Sempere

2012

European Journal of Endocrinology

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Puberty is a fascinating developmental phase that involves the attainment of reproductive capacity and the completion of sexual and somatic maturation. As a life-changing event, puberty onset is precisely controlled by interconnected regulatory pathways that are sensitive to numerous endogenous signals and environmental cues. The mechanisms of normal puberty and its potential deviations have been thoroughly studied in humans and model species. Yet, characterization of the neurobiological basis of puberty is still incomplete. Progress on this front is not only relevant from a physiological perspective but would also help to unravel the underlying causes for the observed changes in the timing of puberty in humans, with a trend for earlier puberty onset, especially in girls. In this review, we will provide a synoptic overview of some recent developments in the field that have deepened our understanding of the neuroendocrine and molecular basis for the control of puberty onset. These include not only the demonstration of the involvement of the hypothalamic Kiss1 system in the control of puberty and its modulation by metabolic cues but also the identification of the roles of other neuropeptide pathways and molecular mediators in the regulation of puberty. In addition, the potential contribution of novel regulatory mechanisms, such as epigenetics, in the central control of puberty will be briefly discussed. Characterization of these novel players and regulatory mechanisms will improve our understanding of the basis of normal puberty and its eventual alterations in various pathological conditions. European Journal of Endocrinology 167 733-747

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Section: Kisspeptins: Major Gatekeepers Of Pubertymentioning

confidence: 76%

Section: Kisspeptins: Major Gatekeepers Of Pubertymentioning

confidence: 93%

Section: Kisspeptins: Major Gatekeepers Of Pubertymentioning

confidence: 99%

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ENDOCRINOLOGY AND ADOLESCENCE: Deciphering puberty: novel partners, novel mechanisms

Tena‐Sempere

2012

European Journal of Endocrinology

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“…To date, the pharmacological actions of NKB on the regulation of pulsatile GNRH/LH secretion remain controversial. The central administration of senktide markedly decreased serum LH levels in ovariectomized rats treated with low levels of estradiol (Sandoval-Guzman & Rance 2004). Inhibitory effects on LH release were also observed after central injection of either NKB or senktide in ovariectomized goats (Wakabayashi et al 2010) and mice ).…”

Section: Discussionmentioning

confidence: 89%

“…In the ewe, activation of NK3R with senktide, a potent and selective NK3R agonist, consistently stimulates LH secretion (Billings et al 2010). In contrast to humans and sheep, senktide suppressed LH secretion in rats (Sandoval-Guzman & Rance 2004) and mice (Castellano et al 2009). …”

Section: Introductionmentioning

confidence: 99%

Prenatal androgen excess enhances stimulation of the GNRH pulse in pubertal female rats

Yan¹,

Yuan²,

Zhao³

et al. 2014

Journal of Endocrinology

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In adolescent girls with polycystic ovary syndrome (PCOS), neuroendocrine derangements manifest after the onset of puberty, characterized by rapid LH pulse frequency. The early mechanism underlying the pubertal regulation of the GNRH/LH pulsatile release in adolescents with PCOS remains uncertain. To determine the effects of prenatal androgen exposure on the activation of GNRH neurons and generation of LH pulse at puberty, we administrated 5a-dihydrotestosterone to pregnant rats and observed serum LH levels and expression of hypothalamic genes in female offspring from postnatal 4 to 8 weeks. The 6-week-old prenatally androgenized (PNA) female rats exhibited an increase in LH pulse frequency. The hypothalamic expression of neurokinin B (Nkb (Tac2)) and Lepr mRNA levels in PNA rats increased remarkably before puberty and remained high during puberty, whereas elevated Kiss1 mRNA levels were detected only after the onset of puberty. Exogenous kisspeptin, NK3R agonist, and leptin triggered tonic stimulation of GNRH neurons and increased LH secretion in 6-week-old PNA rats. Leptin upregulated Kiss1 mRNA levels in the hypothalamus of pubertal PNA rats; however, pretreatment with a kisspeptin antagonist failed to suppress the elevated serum LH stimulated by leptin, indicating that the stimulatory effects of leptin may be conveyed indirectly to GNRH neurons via other neural components within the GNRH neuronal network, rather than through the kisspeptin-GPR54 pathway. These findings validate the hypotheses that NKB and leptin play an essential role in the activation of GNRH neurons and initiation of increased LH pulse frequency in PNA female rats at puberty and that kisspeptin may coordinate their stimulatory effects on LH release.

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Morphologic evidence that neurokinin B modulates gonadotropin‐releasing hormone secretion via neurokinin 3 receptors in the rat median eminence

Krajewski

Anderson

Iles-Shih

et al. 2005

J of Comparative Neurology

177

184

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Recent studies suggest that arcuate neurokinin B (NKB) neurons play a role in the regulation of gonadotropin secretion, but there is little information on the relationship between these neurons and the hypothalamic reproductive axis. In the present study, dual-label fluorescent immunohistochemistry was used to visualize the relationship between gonadotropin-releasing hormone (GnRH) neurons and either proNKB or NK3 receptor (NK3R) immunoreactivity. Immunocytochemistry was also combined with i.p. injections of the fluorescent retrograde tracer aminostilbamidine to determine whether arcuate neuroendocrine neurons expressed either proNKB or NK3R. A dense interweaving and close apposition of GnRH and proNKB-immunoreactive (ir) fibers was observed within the rat median eminence, where GnRH axons expressed NK3R immunoreactivity. These data provide morphological evidence that NKB neurons could influence GnRH secretion via interaction with NK3R in the rat median eminence. Colocalization of GnRH and NK3R was also identified in fiber tracts converging within the organum vasculosum of the lamina terminalis. In contrast, only a small number (16%) of GnRH-ir somata exhibited NK3R staining. ProNKB and NK3R-ir somata were identified within the arcuate nucleus, but none of these neurons were labeled by aminostilbamidine. Thus, we found no evidence that arcuate NKB neurons project to the primary capillary plexus of the portal system. Arcuate neuroendocrine neurons, however, were surrounded and closely apposed by proNKB-ir puncta and fibers. These data suggest that NKB neurons could indirectly influence anterior pituitary function by inputs to arcuate neuroendocrine neurons, but through a receptor other than NK3R. Our results provide an anatomic framework for putative interactions between NKB neurons and the hypothalamic reproductive axis.

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Central injection of senktide, an NK3 receptor agonist, or neuropeptide Y inhibits LH secretion and induces different patterns of Fos expression in the rat hypothalamus

Cited by 149 publications

References 38 publications

ENDOCRINOLOGY AND ADOLESCENCE: Deciphering puberty: novel partners, novel mechanisms

ENDOCRINOLOGY AND ADOLESCENCE: Deciphering puberty: novel partners, novel mechanisms

Prenatal androgen excess enhances stimulation of the GNRH pulse in pubertal female rats

Morphologic evidence that neurokinin B modulates gonadotropin‐releasing hormone secretion via neurokinin 3 receptors in the rat median eminence

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