Effects of season and estradiol on KNDy neuron peptides, colocalization with D2 dopamine receptors, and dopaminergic inputs in the ewe

Peyton Weems, Jeremy Smith, Iain J. Clarke, Lique M. Coolen, Robert L. Goodman, Michael N. Lehman

    Research output: Contribution to journalArticle

    11 Citations (Scopus)

    Abstract

    Seasonal reproduction in sheep is primarily due to a dramatic increase in the ability of estradiol (E2) to inhibit the pulsatile secretion of gonadotropin-releasing hormone (GnRH) during the nonbreeding season [anestrus (ANS)]. Recent findings suggest that kisspeptin/neurokinin B/dynorphin (KNDy) neurons of the arcuate nucleus (ARC) play a key role in conveying this negative feedback influence, with dopaminergic projections from the retrochiasmatic area acting upon KNDy cells to decrease kisspeptin release and thus inhibit GnRH pulses. However, several questions remain unanswered: (1) Are the coexpressed KNDy peptides, neurokinin B (NKB) and dynorphin, under seasonal regulation similar to kisspeptin? (2) Are seasonal changes in these peptides and their colocalization of D2 dopamine receptors (D2Rs) steroid dependent? and (3) Do KNDy neurons receive direct input from dopaminergic terminals? We used dual- and triple-label immunofluorescence to analyze brain sections through the ARC of ovariectomized (OVX) and OVX plus E2 ewes perfused during either the breeding season or ANS. Results showed (1) steroid-dependent and steroid-independent seasonal changes in kisspeptin and NKB, but not dynorphin, immunoreactivity; (2) increased D2R coexpression during ANS that was dependent on the presence of E2; and (3) evidence that KNDy cells receive direct contact from dopaminergic terminals and that this input increases during ANS. These results support the hypothesis that dopamine acts to inhibit GnRH secretion inANSby directly suppressing the activity ofARCKNDy neurons, and implicateNKB aswell as kisspeptin in seasonal shifts in E2-negative feedback in the sheep.

    Original languageEnglish
    Pages (from-to)831-841
    Number of pages11
    JournalEndocrinology
    Volume158
    Issue number4
    DOIs
    Publication statusPublished - 1 Apr 2017

    Fingerprint

    Neurokinin B
    Kisspeptins
    Dynorphins
    Dopamine D2 Receptors
    Estradiol
    Neurons
    Anestrus
    Peptides
    Gonadotropin-Releasing Hormone
    Arcuate Nucleus of Hypothalamus
    Steroids
    Sheep
    Breeding
    Fluorescent Antibody Technique
    Reproduction
    Dopamine

    Cite this

    Weems, Peyton ; Smith, Jeremy ; Clarke, Iain J. ; Coolen, Lique M. ; Goodman, Robert L. ; Lehman, Michael N. / Effects of season and estradiol on KNDy neuron peptides, colocalization with D2 dopamine receptors, and dopaminergic inputs in the ewe. In: Endocrinology. 2017 ; Vol. 158, No. 4. pp. 831-841.
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    abstract = "Seasonal reproduction in sheep is primarily due to a dramatic increase in the ability of estradiol (E2) to inhibit the pulsatile secretion of gonadotropin-releasing hormone (GnRH) during the nonbreeding season [anestrus (ANS)]. Recent findings suggest that kisspeptin/neurokinin B/dynorphin (KNDy) neurons of the arcuate nucleus (ARC) play a key role in conveying this negative feedback influence, with dopaminergic projections from the retrochiasmatic area acting upon KNDy cells to decrease kisspeptin release and thus inhibit GnRH pulses. However, several questions remain unanswered: (1) Are the coexpressed KNDy peptides, neurokinin B (NKB) and dynorphin, under seasonal regulation similar to kisspeptin? (2) Are seasonal changes in these peptides and their colocalization of D2 dopamine receptors (D2Rs) steroid dependent? and (3) Do KNDy neurons receive direct input from dopaminergic terminals? We used dual- and triple-label immunofluorescence to analyze brain sections through the ARC of ovariectomized (OVX) and OVX plus E2 ewes perfused during either the breeding season or ANS. Results showed (1) steroid-dependent and steroid-independent seasonal changes in kisspeptin and NKB, but not dynorphin, immunoreactivity; (2) increased D2R coexpression during ANS that was dependent on the presence of E2; and (3) evidence that KNDy cells receive direct contact from dopaminergic terminals and that this input increases during ANS. These results support the hypothesis that dopamine acts to inhibit GnRH secretion inANSby directly suppressing the activity ofARCKNDy neurons, and implicateNKB aswell as kisspeptin in seasonal shifts in E2-negative feedback in the sheep.",
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    Effects of season and estradiol on KNDy neuron peptides, colocalization with D2 dopamine receptors, and dopaminergic inputs in the ewe. / Weems, Peyton; Smith, Jeremy; Clarke, Iain J.; Coolen, Lique M.; Goodman, Robert L.; Lehman, Michael N.

    In: Endocrinology, Vol. 158, No. 4, 01.04.2017, p. 831-841.

    Research output: Contribution to journalArticle

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    AU - Weems, Peyton

    AU - Smith, Jeremy

    AU - Clarke, Iain J.

    AU - Coolen, Lique M.

    AU - Goodman, Robert L.

    AU - Lehman, Michael N.

    PY - 2017/4/1

    Y1 - 2017/4/1

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