Gonadotropin-inhibitory hormone (GnIH) secretion into the ovine hypophyseal portal system

Jeremy T. Smith, I. Ross Young, Johannes D Veldhuis, Iain J. Clarke

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

GnIH was first identified in avian species, and there is now strong evidence that it is operant in mammals as an inhibitor of reproduction. Mammalian gonadotropin-inhibitory hormone (GnIH)-3 is encoded by the RFRP gene in neurons of the dorsomedial nucleus. These neurons project to the median eminence, predicting a role as a secreted neurohormone and regulation of the pituitary gonadotropes. To determine whether GnIH-3 is a secreted neurohormone, we measured its concentration in hypophyseal portal blood in ewes during the nonbreeding (anestrous) season and during the luteal and follicular phases of the estrous cycle in the breeding season. Paired portal and jugular blood samples were collected and plasma prepared for RIA using an ovine GnIH-3 antibody. Pulsatile GnIH-3 secretion was observed in the portal blood of all animals. Mean GnIH-3 pulse amplitude and pulse frequency was higher during the nonbreeding season. GnIH-3 was virtually undetectable in peripheral blood plasma. There was a lack of association between secretory pulses of GnIH-3 (portal) and LH (peripheral). To determine the role of secreted GnIH-3, we examined its effects on GnRH-stimulated LH secretion in hypothalamo-pituitary- disconnected ewes; a significant reduction in the LH response to GnRH was observed. Finally, to identify cellular targets in the pituitary, the expression of GnIH receptor [G protein-coupled receptor 147 (GPR147)] in fractions enriched for gonadotropes somatotropes, and lactotropes was examined; expression was observed in each cell type. These data show GnIH-3 is secreted into portal blood to act on pituitary gonadotropes, reducing the action of GnRH.

Original languageEnglish (US)
Pages (from-to)3368-3375
Number of pages8
JournalEndocrinology
Volume153
Issue number7
DOIs
StatePublished - Jul 2012

Fingerprint

Portal System
Gonadotropins
Sheep
Hormones
Gonadotropin-Releasing Hormone
Neurotransmitter Agents
Pulse
Mediodorsal Thalamic Nucleus
Pituitary Gonadotropins
Neurons
Median Eminence
Follicular Phase
Estrous Cycle
Luteal Phase
G-Protein-Coupled Receptors
Breeding
Reproduction
Mammals
Neck

ASJC Scopus subject areas

  • Endocrinology

Cite this

Smith, J. T., Young, I. R., Veldhuis, J. D., & Clarke, I. J. (2012). Gonadotropin-inhibitory hormone (GnIH) secretion into the ovine hypophyseal portal system. Endocrinology, 153(7), 3368-3375. https://doi.org/10.1210/en.2012-1088

Gonadotropin-inhibitory hormone (GnIH) secretion into the ovine hypophyseal portal system. / Smith, Jeremy T.; Young, I. Ross; Veldhuis, Johannes D; Clarke, Iain J.

In: Endocrinology, Vol. 153, No. 7, 07.2012, p. 3368-3375.

Research output: Contribution to journalArticle

Smith, JT, Young, IR, Veldhuis, JD & Clarke, IJ 2012, 'Gonadotropin-inhibitory hormone (GnIH) secretion into the ovine hypophyseal portal system', Endocrinology, vol. 153, no. 7, pp. 3368-3375. https://doi.org/10.1210/en.2012-1088
Smith, Jeremy T. ; Young, I. Ross ; Veldhuis, Johannes D ; Clarke, Iain J. / Gonadotropin-inhibitory hormone (GnIH) secretion into the ovine hypophyseal portal system. In: Endocrinology. 2012 ; Vol. 153, No. 7. pp. 3368-3375.
@article{95af8289e91243e0840eae979d62293c,
title = "Gonadotropin-inhibitory hormone (GnIH) secretion into the ovine hypophyseal portal system",
abstract = "GnIH was first identified in avian species, and there is now strong evidence that it is operant in mammals as an inhibitor of reproduction. Mammalian gonadotropin-inhibitory hormone (GnIH)-3 is encoded by the RFRP gene in neurons of the dorsomedial nucleus. These neurons project to the median eminence, predicting a role as a secreted neurohormone and regulation of the pituitary gonadotropes. To determine whether GnIH-3 is a secreted neurohormone, we measured its concentration in hypophyseal portal blood in ewes during the nonbreeding (anestrous) season and during the luteal and follicular phases of the estrous cycle in the breeding season. Paired portal and jugular blood samples were collected and plasma prepared for RIA using an ovine GnIH-3 antibody. Pulsatile GnIH-3 secretion was observed in the portal blood of all animals. Mean GnIH-3 pulse amplitude and pulse frequency was higher during the nonbreeding season. GnIH-3 was virtually undetectable in peripheral blood plasma. There was a lack of association between secretory pulses of GnIH-3 (portal) and LH (peripheral). To determine the role of secreted GnIH-3, we examined its effects on GnRH-stimulated LH secretion in hypothalamo-pituitary- disconnected ewes; a significant reduction in the LH response to GnRH was observed. Finally, to identify cellular targets in the pituitary, the expression of GnIH receptor [G protein-coupled receptor 147 (GPR147)] in fractions enriched for gonadotropes somatotropes, and lactotropes was examined; expression was observed in each cell type. These data show GnIH-3 is secreted into portal blood to act on pituitary gonadotropes, reducing the action of GnRH.",
author = "Smith, {Jeremy T.} and Young, {I. Ross} and Veldhuis, {Johannes D} and Clarke, {Iain J.}",
year = "2012",
month = "7",
doi = "10.1210/en.2012-1088",
language = "English (US)",
volume = "153",
pages = "3368--3375",
journal = "Endocrinology",
issn = "0013-7227",
publisher = "The Endocrine Society",
number = "7",

}

TY - JOUR

T1 - Gonadotropin-inhibitory hormone (GnIH) secretion into the ovine hypophyseal portal system

AU - Smith, Jeremy T.

AU - Young, I. Ross

AU - Veldhuis, Johannes D

AU - Clarke, Iain J.

PY - 2012/7

Y1 - 2012/7

N2 - GnIH was first identified in avian species, and there is now strong evidence that it is operant in mammals as an inhibitor of reproduction. Mammalian gonadotropin-inhibitory hormone (GnIH)-3 is encoded by the RFRP gene in neurons of the dorsomedial nucleus. These neurons project to the median eminence, predicting a role as a secreted neurohormone and regulation of the pituitary gonadotropes. To determine whether GnIH-3 is a secreted neurohormone, we measured its concentration in hypophyseal portal blood in ewes during the nonbreeding (anestrous) season and during the luteal and follicular phases of the estrous cycle in the breeding season. Paired portal and jugular blood samples were collected and plasma prepared for RIA using an ovine GnIH-3 antibody. Pulsatile GnIH-3 secretion was observed in the portal blood of all animals. Mean GnIH-3 pulse amplitude and pulse frequency was higher during the nonbreeding season. GnIH-3 was virtually undetectable in peripheral blood plasma. There was a lack of association between secretory pulses of GnIH-3 (portal) and LH (peripheral). To determine the role of secreted GnIH-3, we examined its effects on GnRH-stimulated LH secretion in hypothalamo-pituitary- disconnected ewes; a significant reduction in the LH response to GnRH was observed. Finally, to identify cellular targets in the pituitary, the expression of GnIH receptor [G protein-coupled receptor 147 (GPR147)] in fractions enriched for gonadotropes somatotropes, and lactotropes was examined; expression was observed in each cell type. These data show GnIH-3 is secreted into portal blood to act on pituitary gonadotropes, reducing the action of GnRH.

AB - GnIH was first identified in avian species, and there is now strong evidence that it is operant in mammals as an inhibitor of reproduction. Mammalian gonadotropin-inhibitory hormone (GnIH)-3 is encoded by the RFRP gene in neurons of the dorsomedial nucleus. These neurons project to the median eminence, predicting a role as a secreted neurohormone and regulation of the pituitary gonadotropes. To determine whether GnIH-3 is a secreted neurohormone, we measured its concentration in hypophyseal portal blood in ewes during the nonbreeding (anestrous) season and during the luteal and follicular phases of the estrous cycle in the breeding season. Paired portal and jugular blood samples were collected and plasma prepared for RIA using an ovine GnIH-3 antibody. Pulsatile GnIH-3 secretion was observed in the portal blood of all animals. Mean GnIH-3 pulse amplitude and pulse frequency was higher during the nonbreeding season. GnIH-3 was virtually undetectable in peripheral blood plasma. There was a lack of association between secretory pulses of GnIH-3 (portal) and LH (peripheral). To determine the role of secreted GnIH-3, we examined its effects on GnRH-stimulated LH secretion in hypothalamo-pituitary- disconnected ewes; a significant reduction in the LH response to GnRH was observed. Finally, to identify cellular targets in the pituitary, the expression of GnIH receptor [G protein-coupled receptor 147 (GPR147)] in fractions enriched for gonadotropes somatotropes, and lactotropes was examined; expression was observed in each cell type. These data show GnIH-3 is secreted into portal blood to act on pituitary gonadotropes, reducing the action of GnRH.

UR - http://www.scopus.com/inward/record.url?scp=84862727773&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84862727773&partnerID=8YFLogxK

U2 - 10.1210/en.2012-1088

DO - 10.1210/en.2012-1088

M3 - Article

VL - 153

SP - 3368

EP - 3375

JO - Endocrinology

JF - Endocrinology

SN - 0013-7227

IS - 7

ER -