Activation of gonadotropin-releasing hormone neurons by kisspeptin as a neuroendocrine switch for the onset of puberty

Seong-Kyu Han, Michelle L Gottsch, Kathy J Lee, Simina M Popa, Jeremy Troy Smith, Sonya K Jakawich, Donald K Clifton, Robert A Steiner, Allan E Herbison

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Abstract

We examined the role of kisspeptin and its receptor, the G-protein-coupled receptor GPR54, in governing the onset of puberty in the mouse. In the adult male and female mouse, kisspeptin (10-100 nM) evoked a remarkably potent, long-lasting depolarization of >90 of gonadotropin-releasing hormone (GnRH)-green fluorescent protein neurons in situ. In contrast, in juvenile [postnatal day 8 (P8) to P19] and prepubertal (P26-P33) male mice, kisspeptin activated only 27 and 44 of GnRH neurons, respectively. This developmental recruitment of GnRH neurons into a kisspeptin-responsive pool was paralleled by an increase in the ability of centrally administered kisspeptin to evoke luteinizing hormone secretion in vivo. To learn more about the mechanisms through which kisspeptin-GPR54 signaling at the GnRH neuron may change over postnatal development, we performed quantitative in situ hybridization for kisspeptin and GPR54 transcripts. Approximately 90 of GnRH neurons were found to express GPR54 mRNA in both juvenile and adult mice, without a detectable difference in the mRNA content between the age groups. In contrast, the expression of KiSS-1 mRNA increased dramatically across the transition from juvenile to adult life in the anteroventral periventricular nucleus (AVPV; p <0.001). These results demonstrate that kisspeptin exerts a potent depolarizing effect on the excitability of almost all adult GnRH neurons and that the responsiveness of GnRH neurons to kisspeptin increases over postnatal development. Together, these observations suggest that activation of GnRH neurons by kisspeptin at puberty reflects a dual process involving an increase in kisspeptin input from the AVPV and a post-transcriptional change in GPR54 signaling within the GnRH neuron.
Original languageEnglish
Pages (from-to)11349 - 11356
Number of pages8
JournalJournal of Neuroscience
Volume25
Issue number49
DOIs
Publication statusPublished - 2005
Externally publishedYes

Cite this

Han, S-K., Gottsch, M. L., Lee, K. J., Popa, S. M., Smith, J. T., Jakawich, S. K., ... Herbison, A. E. (2005). Activation of gonadotropin-releasing hormone neurons by kisspeptin as a neuroendocrine switch for the onset of puberty. Journal of Neuroscience, 25(49), 11349 - 11356. https://doi.org/10.1523/JNEUROSCI.3328-05.2005
Han, Seong-Kyu ; Gottsch, Michelle L ; Lee, Kathy J ; Popa, Simina M ; Smith, Jeremy Troy ; Jakawich, Sonya K ; Clifton, Donald K ; Steiner, Robert A ; Herbison, Allan E. / Activation of gonadotropin-releasing hormone neurons by kisspeptin as a neuroendocrine switch for the onset of puberty. In: Journal of Neuroscience. 2005 ; Vol. 25, No. 49. pp. 11349 - 11356.
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title = "Activation of gonadotropin-releasing hormone neurons by kisspeptin as a neuroendocrine switch for the onset of puberty",
abstract = "We examined the role of kisspeptin and its receptor, the G-protein-coupled receptor GPR54, in governing the onset of puberty in the mouse. In the adult male and female mouse, kisspeptin (10-100 nM) evoked a remarkably potent, long-lasting depolarization of >90 of gonadotropin-releasing hormone (GnRH)-green fluorescent protein neurons in situ. In contrast, in juvenile [postnatal day 8 (P8) to P19] and prepubertal (P26-P33) male mice, kisspeptin activated only 27 and 44 of GnRH neurons, respectively. This developmental recruitment of GnRH neurons into a kisspeptin-responsive pool was paralleled by an increase in the ability of centrally administered kisspeptin to evoke luteinizing hormone secretion in vivo. To learn more about the mechanisms through which kisspeptin-GPR54 signaling at the GnRH neuron may change over postnatal development, we performed quantitative in situ hybridization for kisspeptin and GPR54 transcripts. Approximately 90 of GnRH neurons were found to express GPR54 mRNA in both juvenile and adult mice, without a detectable difference in the mRNA content between the age groups. In contrast, the expression of KiSS-1 mRNA increased dramatically across the transition from juvenile to adult life in the anteroventral periventricular nucleus (AVPV; p <0.001). These results demonstrate that kisspeptin exerts a potent depolarizing effect on the excitability of almost all adult GnRH neurons and that the responsiveness of GnRH neurons to kisspeptin increases over postnatal development. Together, these observations suggest that activation of GnRH neurons by kisspeptin at puberty reflects a dual process involving an increase in kisspeptin input from the AVPV and a post-transcriptional change in GPR54 signaling within the GnRH neuron.",
author = "Seong-Kyu Han and Gottsch, {Michelle L} and Lee, {Kathy J} and Popa, {Simina M} and Smith, {Jeremy Troy} and Jakawich, {Sonya K} and Clifton, {Donald K} and Steiner, {Robert A} and Herbison, {Allan E}",
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Han, S-K, 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', Journal of Neuroscience, vol. 25, no. 49, pp. 11349 - 11356. https://doi.org/10.1523/JNEUROSCI.3328-05.2005

Activation of gonadotropin-releasing hormone neurons by kisspeptin as a neuroendocrine switch for the onset of puberty. / Han, Seong-Kyu; Gottsch, Michelle L; Lee, Kathy J; Popa, Simina M; Smith, Jeremy Troy; Jakawich, Sonya K; Clifton, Donald K; Steiner, Robert A; Herbison, Allan E.

In: Journal of Neuroscience, Vol. 25, No. 49, 2005, p. 11349 - 11356.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Activation of gonadotropin-releasing hormone neurons by kisspeptin as a neuroendocrine switch for the onset of puberty

AU - Han, Seong-Kyu

AU - Gottsch, Michelle L

AU - Lee, Kathy J

AU - Popa, Simina M

AU - Smith, Jeremy Troy

AU - Jakawich, Sonya K

AU - Clifton, Donald K

AU - Steiner, Robert A

AU - Herbison, Allan E

PY - 2005

Y1 - 2005

N2 - We examined the role of kisspeptin and its receptor, the G-protein-coupled receptor GPR54, in governing the onset of puberty in the mouse. In the adult male and female mouse, kisspeptin (10-100 nM) evoked a remarkably potent, long-lasting depolarization of >90 of gonadotropin-releasing hormone (GnRH)-green fluorescent protein neurons in situ. In contrast, in juvenile [postnatal day 8 (P8) to P19] and prepubertal (P26-P33) male mice, kisspeptin activated only 27 and 44 of GnRH neurons, respectively. This developmental recruitment of GnRH neurons into a kisspeptin-responsive pool was paralleled by an increase in the ability of centrally administered kisspeptin to evoke luteinizing hormone secretion in vivo. To learn more about the mechanisms through which kisspeptin-GPR54 signaling at the GnRH neuron may change over postnatal development, we performed quantitative in situ hybridization for kisspeptin and GPR54 transcripts. Approximately 90 of GnRH neurons were found to express GPR54 mRNA in both juvenile and adult mice, without a detectable difference in the mRNA content between the age groups. In contrast, the expression of KiSS-1 mRNA increased dramatically across the transition from juvenile to adult life in the anteroventral periventricular nucleus (AVPV; p <0.001). These results demonstrate that kisspeptin exerts a potent depolarizing effect on the excitability of almost all adult GnRH neurons and that the responsiveness of GnRH neurons to kisspeptin increases over postnatal development. Together, these observations suggest that activation of GnRH neurons by kisspeptin at puberty reflects a dual process involving an increase in kisspeptin input from the AVPV and a post-transcriptional change in GPR54 signaling within the GnRH neuron.

AB - We examined the role of kisspeptin and its receptor, the G-protein-coupled receptor GPR54, in governing the onset of puberty in the mouse. In the adult male and female mouse, kisspeptin (10-100 nM) evoked a remarkably potent, long-lasting depolarization of >90 of gonadotropin-releasing hormone (GnRH)-green fluorescent protein neurons in situ. In contrast, in juvenile [postnatal day 8 (P8) to P19] and prepubertal (P26-P33) male mice, kisspeptin activated only 27 and 44 of GnRH neurons, respectively. This developmental recruitment of GnRH neurons into a kisspeptin-responsive pool was paralleled by an increase in the ability of centrally administered kisspeptin to evoke luteinizing hormone secretion in vivo. To learn more about the mechanisms through which kisspeptin-GPR54 signaling at the GnRH neuron may change over postnatal development, we performed quantitative in situ hybridization for kisspeptin and GPR54 transcripts. Approximately 90 of GnRH neurons were found to express GPR54 mRNA in both juvenile and adult mice, without a detectable difference in the mRNA content between the age groups. In contrast, the expression of KiSS-1 mRNA increased dramatically across the transition from juvenile to adult life in the anteroventral periventricular nucleus (AVPV; p <0.001). These results demonstrate that kisspeptin exerts a potent depolarizing effect on the excitability of almost all adult GnRH neurons and that the responsiveness of GnRH neurons to kisspeptin increases over postnatal development. Together, these observations suggest that activation of GnRH neurons by kisspeptin at puberty reflects a dual process involving an increase in kisspeptin input from the AVPV and a post-transcriptional change in GPR54 signaling within the GnRH neuron.

UR - http://www.jneurosci.org/cgi/reprint/25/49/11349

U2 - 10.1523/JNEUROSCI.3328-05.2005

DO - 10.1523/JNEUROSCI.3328-05.2005

M3 - Article

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JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

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