Hypothalamic KISS1 expression, gonadotrophin-releasing hormone and neurotransmitter innervation vary with stress and sensitivity in macaques

Cynthia Bethea, A. Kim, Arubala Reddy, A. Chin, S. C. Bethea, J. L. Cameron

    Research output: Contribution to journalArticle

    4 Citations (Scopus)

    Abstract

    The present study examined the effect of short-term psychosocial and metabolic stress in a monkey model of stress-induced amenorrhaea on the hypothalamic-pituitary-gonadal axis. KISS1 expression was determined by in situ hybridisation in the infundibular arcuate nucleus. Downstream of KISS1, gonadotrophin-releasing hormone (GnRH) axons in lateral areas rostral to the infundibular recess, serum luteinising hormone (LH) and serum oestradiol were measured by immunohistochemistry and radioimmunoassay. Upstream of KISS1, norepinephrine axons in the rostral arcuate nucleus and serotonin axons in the anterior hypothalamus and periaqueductal grey were measured by immunohistochemistry. Female cynomolgus macaques (Macaca fascicularis) characterised as highly stress resilient (HSR) or stress sensitive (SS) were examined. After characterisation of stress sensitivity, monkeys were either not stressed, or mildly stressed for 5 days before euthanasia in the early follicular phase. Stress consisted of 5 days of 20% food reduction in a novel room with unfamiliar conspecifics. There was a significant increase in KISS1 expression in HSR and SS animals in the presence versus absence of stress (P = 0.005). GnRH axon density increased with stress in HSR and SS animals (P = 0.015), whereas LH showed a gradual but nonsignificant increase with stress. Oestradiol trended higher in HSR animals and there was no effect of stress (P = 0.83). Norepinephrine axon density (marked with dopamine β-hydroxylase) increased with stress in both HSR and SS groups (P ≤ 0.002), whereas serotonin axon density was higher in HSR compared to SS animals and there was no effect of stress (P = 0.03). The ratio of dopamine β-hydroxylase/oestradiol correlated with KISS1 (P = 0.052) and GnRH correlated with serum LH (P = 0.039). In conclusion, oestradiol inhibited KISS1 in the absence of stress, although stress increased norepinephrine, which may over-ride oestradiol inhibition of KISS1 expression. We speculate that neural pathways transduce stress to KISS1 neurones, which changes their sensitivity to oestradiol.

    Original languageEnglish (US)
    Pages (from-to)267-281
    Number of pages15
    JournalJournal of Neuroendocrinology
    Volume26
    Issue number5
    DOIs
    StatePublished - 2014

    Fingerprint

    Macaca
    Gonadotropin-Releasing Hormone
    Neurotransmitter Agents
    Axons
    Estradiol
    Arcuate Nucleus of Hypothalamus
    Luteinizing Hormone
    Norepinephrine
    Mixed Function Oxygenases
    Haplorhini
    Dopamine
    Serotonin
    Serum
    Immunohistochemistry
    Anterior Hypothalamus
    Neural Pathways
    Periaqueductal Gray
    Physiological Stress
    Follicular Phase
    Euthanasia

    Keywords

    • Amenorrhaea
    • GnRH
    • KISS1
    • LH
    • Macaques
    • Norepinephrine
    • Oestrogen
    • Resilience
    • Serotonin
    • Stress

    ASJC Scopus subject areas

    • Endocrinology
    • Endocrinology, Diabetes and Metabolism
    • Endocrine and Autonomic Systems
    • Cellular and Molecular Neuroscience
    • Medicine(all)

    Cite this

    Hypothalamic KISS1 expression, gonadotrophin-releasing hormone and neurotransmitter innervation vary with stress and sensitivity in macaques. / Bethea, Cynthia; Kim, A.; Reddy, Arubala; Chin, A.; Bethea, S. C.; Cameron, J. L.

    In: Journal of Neuroendocrinology, Vol. 26, No. 5, 2014, p. 267-281.

    Research output: Contribution to journalArticle

    @article{713fe57d1fe14d3fb2280260e393e52e,
    title = "Hypothalamic KISS1 expression, gonadotrophin-releasing hormone and neurotransmitter innervation vary with stress and sensitivity in macaques",
    abstract = "The present study examined the effect of short-term psychosocial and metabolic stress in a monkey model of stress-induced amenorrhaea on the hypothalamic-pituitary-gonadal axis. KISS1 expression was determined by in situ hybridisation in the infundibular arcuate nucleus. Downstream of KISS1, gonadotrophin-releasing hormone (GnRH) axons in lateral areas rostral to the infundibular recess, serum luteinising hormone (LH) and serum oestradiol were measured by immunohistochemistry and radioimmunoassay. Upstream of KISS1, norepinephrine axons in the rostral arcuate nucleus and serotonin axons in the anterior hypothalamus and periaqueductal grey were measured by immunohistochemistry. Female cynomolgus macaques (Macaca fascicularis) characterised as highly stress resilient (HSR) or stress sensitive (SS) were examined. After characterisation of stress sensitivity, monkeys were either not stressed, or mildly stressed for 5 days before euthanasia in the early follicular phase. Stress consisted of 5 days of 20{\%} food reduction in a novel room with unfamiliar conspecifics. There was a significant increase in KISS1 expression in HSR and SS animals in the presence versus absence of stress (P = 0.005). GnRH axon density increased with stress in HSR and SS animals (P = 0.015), whereas LH showed a gradual but nonsignificant increase with stress. Oestradiol trended higher in HSR animals and there was no effect of stress (P = 0.83). Norepinephrine axon density (marked with dopamine β-hydroxylase) increased with stress in both HSR and SS groups (P ≤ 0.002), whereas serotonin axon density was higher in HSR compared to SS animals and there was no effect of stress (P = 0.03). The ratio of dopamine β-hydroxylase/oestradiol correlated with KISS1 (P = 0.052) and GnRH correlated with serum LH (P = 0.039). In conclusion, oestradiol inhibited KISS1 in the absence of stress, although stress increased norepinephrine, which may over-ride oestradiol inhibition of KISS1 expression. We speculate that neural pathways transduce stress to KISS1 neurones, which changes their sensitivity to oestradiol.",
    keywords = "Amenorrhaea, GnRH, KISS1, LH, Macaques, Norepinephrine, Oestrogen, Resilience, Serotonin, Stress",
    author = "Cynthia Bethea and A. Kim and Arubala Reddy and A. Chin and Bethea, {S. C.} and Cameron, {J. L.}",
    year = "2014",
    doi = "10.1111/jne.12146",
    language = "English (US)",
    volume = "26",
    pages = "267--281",
    journal = "Journal of Neuroendocrinology",
    issn = "0953-8194",
    publisher = "Wiley-Blackwell",
    number = "5",

    }

    TY - JOUR

    T1 - Hypothalamic KISS1 expression, gonadotrophin-releasing hormone and neurotransmitter innervation vary with stress and sensitivity in macaques

    AU - Bethea, Cynthia

    AU - Kim, A.

    AU - Reddy, Arubala

    AU - Chin, A.

    AU - Bethea, S. C.

    AU - Cameron, J. L.

    PY - 2014

    Y1 - 2014

    N2 - The present study examined the effect of short-term psychosocial and metabolic stress in a monkey model of stress-induced amenorrhaea on the hypothalamic-pituitary-gonadal axis. KISS1 expression was determined by in situ hybridisation in the infundibular arcuate nucleus. Downstream of KISS1, gonadotrophin-releasing hormone (GnRH) axons in lateral areas rostral to the infundibular recess, serum luteinising hormone (LH) and serum oestradiol were measured by immunohistochemistry and radioimmunoassay. Upstream of KISS1, norepinephrine axons in the rostral arcuate nucleus and serotonin axons in the anterior hypothalamus and periaqueductal grey were measured by immunohistochemistry. Female cynomolgus macaques (Macaca fascicularis) characterised as highly stress resilient (HSR) or stress sensitive (SS) were examined. After characterisation of stress sensitivity, monkeys were either not stressed, or mildly stressed for 5 days before euthanasia in the early follicular phase. Stress consisted of 5 days of 20% food reduction in a novel room with unfamiliar conspecifics. There was a significant increase in KISS1 expression in HSR and SS animals in the presence versus absence of stress (P = 0.005). GnRH axon density increased with stress in HSR and SS animals (P = 0.015), whereas LH showed a gradual but nonsignificant increase with stress. Oestradiol trended higher in HSR animals and there was no effect of stress (P = 0.83). Norepinephrine axon density (marked with dopamine β-hydroxylase) increased with stress in both HSR and SS groups (P ≤ 0.002), whereas serotonin axon density was higher in HSR compared to SS animals and there was no effect of stress (P = 0.03). The ratio of dopamine β-hydroxylase/oestradiol correlated with KISS1 (P = 0.052) and GnRH correlated with serum LH (P = 0.039). In conclusion, oestradiol inhibited KISS1 in the absence of stress, although stress increased norepinephrine, which may over-ride oestradiol inhibition of KISS1 expression. We speculate that neural pathways transduce stress to KISS1 neurones, which changes their sensitivity to oestradiol.

    AB - The present study examined the effect of short-term psychosocial and metabolic stress in a monkey model of stress-induced amenorrhaea on the hypothalamic-pituitary-gonadal axis. KISS1 expression was determined by in situ hybridisation in the infundibular arcuate nucleus. Downstream of KISS1, gonadotrophin-releasing hormone (GnRH) axons in lateral areas rostral to the infundibular recess, serum luteinising hormone (LH) and serum oestradiol were measured by immunohistochemistry and radioimmunoassay. Upstream of KISS1, norepinephrine axons in the rostral arcuate nucleus and serotonin axons in the anterior hypothalamus and periaqueductal grey were measured by immunohistochemistry. Female cynomolgus macaques (Macaca fascicularis) characterised as highly stress resilient (HSR) or stress sensitive (SS) were examined. After characterisation of stress sensitivity, monkeys were either not stressed, or mildly stressed for 5 days before euthanasia in the early follicular phase. Stress consisted of 5 days of 20% food reduction in a novel room with unfamiliar conspecifics. There was a significant increase in KISS1 expression in HSR and SS animals in the presence versus absence of stress (P = 0.005). GnRH axon density increased with stress in HSR and SS animals (P = 0.015), whereas LH showed a gradual but nonsignificant increase with stress. Oestradiol trended higher in HSR animals and there was no effect of stress (P = 0.83). Norepinephrine axon density (marked with dopamine β-hydroxylase) increased with stress in both HSR and SS groups (P ≤ 0.002), whereas serotonin axon density was higher in HSR compared to SS animals and there was no effect of stress (P = 0.03). The ratio of dopamine β-hydroxylase/oestradiol correlated with KISS1 (P = 0.052) and GnRH correlated with serum LH (P = 0.039). In conclusion, oestradiol inhibited KISS1 in the absence of stress, although stress increased norepinephrine, which may over-ride oestradiol inhibition of KISS1 expression. We speculate that neural pathways transduce stress to KISS1 neurones, which changes their sensitivity to oestradiol.

    KW - Amenorrhaea

    KW - GnRH

    KW - KISS1

    KW - LH

    KW - Macaques

    KW - Norepinephrine

    KW - Oestrogen

    KW - Resilience

    KW - Serotonin

    KW - Stress

    UR - http://www.scopus.com/inward/record.url?scp=84898453988&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=84898453988&partnerID=8YFLogxK

    U2 - 10.1111/jne.12146

    DO - 10.1111/jne.12146

    M3 - Article

    VL - 26

    SP - 267

    EP - 281

    JO - Journal of Neuroendocrinology

    JF - Journal of Neuroendocrinology

    SN - 0953-8194

    IS - 5

    ER -