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Evidence of a role for kisspeptin and neurokinin B in puberty of female sheep.

ABSTRACT: Puberty onset in female sheep is marked by a decrease in estradiol-negative feedback, allowing for the increase in GnRH and LH pulses that heralds the first ovulation. Based on recent genetic studies in humans, two possible neuropeptides that could promote puberty onset are kisspeptin and neurokinin B (NKB). Our first experiment determined whether the NKB agonist, senktide, could stimulate LH secretion in prepubertal ewes. A second study used prepubertal and postpubertal ewes that were intact or ovariectomized (OVX) to test the hypothesis that expression of kisspeptin and NKB in the arcuate nucleus increased postpubertally. For comparison, kisspeptin and NKB expression in age-matched intact, and castrated males were also examined. In experiment 1, the percentage of ewes showing an LH pulse immediately after injection of senktide (100 ?g, 60%; 500 ?g, 100%) was greater than that for water-injected controls (experiment 1a, 25%; experiment 1b, 20%). In experiment 2, kisspeptin-positive cell numbers in the arcuate nucleus increased after puberty in intact females and were increased by OVX in prepubertal but not postpubertal ewes. Changes in kisspeptin cell numbers were paralleled by changes in kisspeptin-close contacts onto GnRH neurons in the medial preoptic area. NKB cell numbers did not differ significantly between intact prepubertal and postpubertal ewes but increased with OVX in both age groups. NKB fiber immunoreactivity was greater in postpubertal than in prepubertal intact ewes. In age-matched males, kisspeptin and NKB cell numbers increased with castration, but decreased with age. These results support the hypothesis that kisspeptin is a gatekeeper to female ovine puberty and raise the possibility that NKB may also play a role, albeit through different means.

SUBMITTER: Nestor CC

PROVIDER: S-EPMC3359609 | biostudies-other | 2012 Jun

REPOSITORIES: biostudies-other

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Evidence of a role for kisspeptin and neurokinin B in puberty of female sheep.

Nestor Casey C CC Briscoe Amanda M S AM Davis Shay M SM Valent Miro M Goodman Robert L RL Hileman Stanley M SM

Endocrinology 20120320 6

Puberty onset in female sheep is marked by a decrease in estradiol-negative feedback, allowing for the increase in GnRH and LH pulses that heralds the first ovulation. Based on recent genetic studies in humans, two possible neuropeptides that could promote puberty onset are kisspeptin and neurokinin B (NKB). Our first experiment determined whether the NKB agonist, senktide, could stimulate LH secretion in prepubertal ewes. A second study used prepubertal and postpubertal ewes that were intact or ...[more]

PMID: 22434087

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Project description:BACKGROUND:The neuropeptide kisspeptin stimulates luteinizing hormone (LH) secretion in healthy adults but not in adults with idiopathic hypogonadotropic hypogonadism. We hypothesized that, in children presenting with delayed or stalled puberty, kisspeptin would elicit LH secretion in those children found on detailed nighttime neuroendocrine profiling to have evidence of emerging reproductive endocrine function. METHODS:Eleven boys and four girls were admitted overnight to assess LH secretion at baseline, after a single intravenous bolus of kisspeptin, and after a single intravenous bolus of gonadotropin-releasing hormone (GnRH). Subjects then received exogenous pulsatile GnRH for 6 days and returned for a second visit to measure responses to kisspeptin and GnRH after this pituitary "priming." Responses to kisspeptin and GnRH were also measured in 5 healthy men. RESULTS:Of the 15 children with delayed/stalled puberty, 6 exhibited at least one spontaneous LH pulse overnight; all of these subjects had clear responses to kisspeptin, as did one additional subject. Seven subjects had no response to kisspeptin, and one subject exhibited an intermediate response. In the children who responded to kisspeptin, the responses had features comparable to those of adult men. CONCLUSION:In this first report of kisspeptin administration to pediatric subjects to our knowledge, children with delayed/stalled puberty showed a wide range of responses, with some showing a robust response and others showing little to no response. Further follow-up will determine whether responses to kisspeptin predict future pubertal entry for children with delayed puberty. TRIAL REGISTRATION:ClinicalTrials.gov NCT01438034 and NCT01952782. FUNDING:NIH Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01 HD043341, R01 HD090071, P50 HD028138), NIH National Center for Advancing Translational (UL1 TR001102), NIH National Institute of Diabetes and Digestive and Kidney Diseases (T32 DK007028), the Massachusetts General Hospital Executive Committee on Research Fund for Medical Discovery, Harvard Catalyst, Doris Duke Charitable Foundation (award 2013110), Charles H. Hood Foundation, Robert and Laura Reynolds MGH Research Scholar Program, and Harvard University. These funding sources had no role in the design of this study and did not have any role in conducting the study, analyses, interpretation of the data, or the decision to submit results.

Dataset Information

Evidence of a role for kisspeptin and neurokinin B in puberty of female sheep.

Publications

Evidence of a role for kisspeptin and neurokinin B in puberty of female sheep.

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