An Increased Intraovarian Synthesis of Nerve Growth Factor and Its Low Affinity Receptor Is a Principal Component of Steroid-Induced Polycystic Ovary in the Rat
Author
dc.contributor.author
Lara Bravo, Hervi
Author
dc.contributor.author
Dissen, G. A.
es_CL
Author
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Leyton Canales, Víctor
es_CL
Author
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Paredes Vargas, Alfonso
es_CL
Author
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Fuenzalida Cruz, Héctor
es_CL
Author
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Fiedler Temer, Jenny
es_CL
Author
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Ojeda, S. R.
es_CL
Admission date
dc.date.accessioned
2014-01-09T19:56:16Z
Available date
dc.date.available
2014-01-09T19:56:16Z
Publication date
dc.date.issued
2000
Cita de ítem
dc.identifier.citation
Endocrinology, 141(3), 1059-1072.
en_US
Identifier
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doi:10.1210/en.141.3.1059
Identifier
dc.identifier.uri
https://repositorio.uchile.cl/handle/2250/126149
General note
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Artículo de publicación ISI
en_US
Abstract
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A form of polycystic ovary (PCO) resembling some aspects of the
human PCO syndrome can be induced in rats by a single injection of
estradiol valerate (EV). An increase in sympathetic outflow to the
ovary precedes, by several weeks, the appearance of cysts, suggesting
the involvement of a neurogenic component in the pathology of this
ovarian dysfunction. The present study was carried out to test the
hypotheses that this change in sympathetic tone is related to an
augmented production of ovarian nerve growth factor (NGF), and that
this abnormally elevated production of NGF contributes to the formation
of ovarian cysts induced by EV. Injection of the steroid resulted
in increased intraovarian synthesis of NGF and its low affinity
receptor, p75 NGFR. The increase was maximal 30 days after EV,
coinciding with the elevation in sympathetic tone to the ovary and
preceding the appearance of follicular cysts. Intraovarian injections
of the retrograde tracer fluorogold combined with in situ hybridization
to detect tyrosine hydroxylase (TH) messenger RNA-containing neurons
in the celiac ganglion revealed that these changes in NGF/p75
NGFR synthesis are accompanied by selective activation of noradrenergic
neurons projecting to the ovary. The levels of RBT2 messenger
RNA, which encodes a b-tubulin presumably involved in slow
axonal transport, were markedly elevated, indicating that EVinduced
formation of ovarian cysts is preceded by functional activation
of celiac ganglion neurons, including those innervating the ovary.
Intraovarian administration of a neutralizing antiserum to NGF in
conjunction with an antisense oligodeoxynucleotide to p75 NGFR, via
Alzet osmotic minipumps, restored estrous cyclicity and ovulatory
capacity in a majority of EV-treated rats. These functional changes
were accompanied by restoration of the number of antral follicles per
ovary that had been depleted by EV and a significant reduction in the
number of both precystic follicles and follicular cysts. The results
indicate that the hyperactivation of ovarian sympathetic nerves seen
in EV-induced PCO is related to an overproduction of NGF and its low
affinity receptor in the gland. They also suggest that activation of this
neurotrophic-neurogenic regulatory loop is a component of the pathological
process by which EV induces cyst formation and anovulation
in rodents. The possibility exists that a similar alteration in neurotrophic
input to the ovary contributes to the etiology and/or maintenance
of the PCO syndrome in humans. (Endocrinology 141: 1059–
1072, 2000)
en_US
Patrocinador
dc.description.sponsorship
Fondo Nacional de Ciencias de
Chile (Project 1961018) and The Rockefeller Foundation (to H.E.L.) and
by NIH Grants HD-24870 (to S.R.O.), and P30 Population Center Grant
HD-18185 and RR-00163 for the operation of the Oregon Regional Primate
Research Center.
An Increased Intraovarian Synthesis of Nerve Growth Factor and Its Low Affinity Receptor Is a Principal Component of Steroid-Induced Polycystic Ovary in the Rat