Evidence for short or ultrashort loop negative feedback of gonadotropin-releasing hormone secretion

V. Padmanabhan, N. P. Evans, G. E. Dahl, K. L. McFadden, David Mauger, F. J. Karsch

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

The present studies tested the hypothesis that either short or ultrashort loop negative feedback regulation of gonadotropin-releasing hormone (GnRH) secretion occurs in the ewe. As part of ongoing studies investigating the regulation of follicle-stimulating-hormone secretion, we obtained the unexpected result that a GnRH antagonist (Nal-Glu) may stimulate GnRH secretion. In that experiment, hypophyseal portal blood was collected from five short-term ovariectomized ewes at 5-min intervals for 6 h before and 6 h after intravenous injection of Nal-Glu (10 μg/kg body weight). An increase in GnRH pulse frequency in association with the blockade of luteinizing hormone (LH) release was evident in 3 of the 5 animals. To determine if an effect of Nal-Glu on episodic GnRH secretion would be more evident in an animal model in which low-frequency pulses of GnRH prevail, the study was repeated in six ewes in the midluteal phase of the estrous cycle and six ovariectomized ewes bearing estradiol and progesterone implants to suppress GnRH release (artificial luteal model). In luteal-phase ewes, administration of Nal-Glu was followed by an increase in GnRH pulse frequency, pulse size and the secretion of GnRH between pulses, and by a blockade of LH release. In ovariectomized ewes treated with estradiol and progesterone, Nal-Glu administration also stimulated GnRH and inhibited LH secretion. Our finding that the GnRH antagonist stimulated GnRH secretion is consistent with the hypothesis that endogenous GnRH may influence its own release via either a short or ultrashort loop feedback mechanism.

Original languageEnglish (US)
Pages (from-to)248-258
Number of pages11
JournalNeuroendocrinology
Volume62
Issue number3
DOIs
StatePublished - Jan 1 1995

Fingerprint

Gonadotropin-Releasing Hormone
Luteinizing Hormone
Hormone Antagonists
Progesterone
Estradiol
Estrous Cycle
Luteal Phase
Corpus Luteum
Follicle Stimulating Hormone
Intravenous Injections
Animal Models
Body Weight
2-naphthylalanyl-glutamic acid

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

Cite this

Padmanabhan, V. ; Evans, N. P. ; Dahl, G. E. ; McFadden, K. L. ; Mauger, David ; Karsch, F. J. / Evidence for short or ultrashort loop negative feedback of gonadotropin-releasing hormone secretion. In: Neuroendocrinology. 1995 ; Vol. 62, No. 3. pp. 248-258.
@article{5e439ffcd00b4005b2e68a83a651da52,
title = "Evidence for short or ultrashort loop negative feedback of gonadotropin-releasing hormone secretion",
abstract = "The present studies tested the hypothesis that either short or ultrashort loop negative feedback regulation of gonadotropin-releasing hormone (GnRH) secretion occurs in the ewe. As part of ongoing studies investigating the regulation of follicle-stimulating-hormone secretion, we obtained the unexpected result that a GnRH antagonist (Nal-Glu) may stimulate GnRH secretion. In that experiment, hypophyseal portal blood was collected from five short-term ovariectomized ewes at 5-min intervals for 6 h before and 6 h after intravenous injection of Nal-Glu (10 μg/kg body weight). An increase in GnRH pulse frequency in association with the blockade of luteinizing hormone (LH) release was evident in 3 of the 5 animals. To determine if an effect of Nal-Glu on episodic GnRH secretion would be more evident in an animal model in which low-frequency pulses of GnRH prevail, the study was repeated in six ewes in the midluteal phase of the estrous cycle and six ovariectomized ewes bearing estradiol and progesterone implants to suppress GnRH release (artificial luteal model). In luteal-phase ewes, administration of Nal-Glu was followed by an increase in GnRH pulse frequency, pulse size and the secretion of GnRH between pulses, and by a blockade of LH release. In ovariectomized ewes treated with estradiol and progesterone, Nal-Glu administration also stimulated GnRH and inhibited LH secretion. Our finding that the GnRH antagonist stimulated GnRH secretion is consistent with the hypothesis that endogenous GnRH may influence its own release via either a short or ultrashort loop feedback mechanism.",
author = "V. Padmanabhan and Evans, {N. P.} and Dahl, {G. E.} and McFadden, {K. L.} and David Mauger and Karsch, {F. J.}",
year = "1995",
month = "1",
day = "1",
doi = "10.1159/000127011",
language = "English (US)",
volume = "62",
pages = "248--258",
journal = "Neuroendocrinology",
issn = "0028-3835",
publisher = "S. Karger AG",
number = "3",

}

Evidence for short or ultrashort loop negative feedback of gonadotropin-releasing hormone secretion. / Padmanabhan, V.; Evans, N. P.; Dahl, G. E.; McFadden, K. L.; Mauger, David; Karsch, F. J.

In: Neuroendocrinology, Vol. 62, No. 3, 01.01.1995, p. 248-258.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Evidence for short or ultrashort loop negative feedback of gonadotropin-releasing hormone secretion

AU - Padmanabhan, V.

AU - Evans, N. P.

AU - Dahl, G. E.

AU - McFadden, K. L.

AU - Mauger, David

AU - Karsch, F. J.

PY - 1995/1/1

Y1 - 1995/1/1

N2 - The present studies tested the hypothesis that either short or ultrashort loop negative feedback regulation of gonadotropin-releasing hormone (GnRH) secretion occurs in the ewe. As part of ongoing studies investigating the regulation of follicle-stimulating-hormone secretion, we obtained the unexpected result that a GnRH antagonist (Nal-Glu) may stimulate GnRH secretion. In that experiment, hypophyseal portal blood was collected from five short-term ovariectomized ewes at 5-min intervals for 6 h before and 6 h after intravenous injection of Nal-Glu (10 μg/kg body weight). An increase in GnRH pulse frequency in association with the blockade of luteinizing hormone (LH) release was evident in 3 of the 5 animals. To determine if an effect of Nal-Glu on episodic GnRH secretion would be more evident in an animal model in which low-frequency pulses of GnRH prevail, the study was repeated in six ewes in the midluteal phase of the estrous cycle and six ovariectomized ewes bearing estradiol and progesterone implants to suppress GnRH release (artificial luteal model). In luteal-phase ewes, administration of Nal-Glu was followed by an increase in GnRH pulse frequency, pulse size and the secretion of GnRH between pulses, and by a blockade of LH release. In ovariectomized ewes treated with estradiol and progesterone, Nal-Glu administration also stimulated GnRH and inhibited LH secretion. Our finding that the GnRH antagonist stimulated GnRH secretion is consistent with the hypothesis that endogenous GnRH may influence its own release via either a short or ultrashort loop feedback mechanism.

AB - The present studies tested the hypothesis that either short or ultrashort loop negative feedback regulation of gonadotropin-releasing hormone (GnRH) secretion occurs in the ewe. As part of ongoing studies investigating the regulation of follicle-stimulating-hormone secretion, we obtained the unexpected result that a GnRH antagonist (Nal-Glu) may stimulate GnRH secretion. In that experiment, hypophyseal portal blood was collected from five short-term ovariectomized ewes at 5-min intervals for 6 h before and 6 h after intravenous injection of Nal-Glu (10 μg/kg body weight). An increase in GnRH pulse frequency in association with the blockade of luteinizing hormone (LH) release was evident in 3 of the 5 animals. To determine if an effect of Nal-Glu on episodic GnRH secretion would be more evident in an animal model in which low-frequency pulses of GnRH prevail, the study was repeated in six ewes in the midluteal phase of the estrous cycle and six ovariectomized ewes bearing estradiol and progesterone implants to suppress GnRH release (artificial luteal model). In luteal-phase ewes, administration of Nal-Glu was followed by an increase in GnRH pulse frequency, pulse size and the secretion of GnRH between pulses, and by a blockade of LH release. In ovariectomized ewes treated with estradiol and progesterone, Nal-Glu administration also stimulated GnRH and inhibited LH secretion. Our finding that the GnRH antagonist stimulated GnRH secretion is consistent with the hypothesis that endogenous GnRH may influence its own release via either a short or ultrashort loop feedback mechanism.

UR - http://www.scopus.com/inward/record.url?scp=0029114405&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029114405&partnerID=8YFLogxK

U2 - 10.1159/000127011

DO - 10.1159/000127011

M3 - Article

VL - 62

SP - 248

EP - 258

JO - Neuroendocrinology

JF - Neuroendocrinology

SN - 0028-3835

IS - 3

ER -