Estrus cyclicity of spinogenesis: Underlying mechanisms

Janine Prange-Kiel, Lars Fester, Lepu Zhou, Hubertus Jarry, Gabriele M. Rune

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Hippocampal spine density varies with the estrus cycle. The cyclic change in estradiol levels in serum was hypothesized to underlie this phenomenon, since treatment of ovariectomized animals with estradiol induced an increase in spine density in hippocampal dendrites of rats, as compared to ovariectomized controls. In contrast, application of estradiol to hippocampal slice cultures did not promote spinogenesis. In addressing this discrepancy, we found that hippocampal neurons themselves are capable of synthesizing estradiol de novo. Estradiol synthesis can be suppressed by aromatase inhibitors and by knock-down of Steroid Acute Regulatory Protein (StAR) and enhanced by substrates of steroidogenesis. Expression of estrogen receptors (ERs) and synaptic proteins, synaptogenesis, and long-term potentiation (LTP) correlated positively with aromatase activity in hippocampal cultures without any difference between genders. All effects due to inhibition of aromatase activity were rescued by application of estradiol to the cultures. Most importantly, gonadotropin- releasing hormone (GnRH) increased estradiol synthesis dose-dependently via an aromatase-mediated mechanism and consistently increased spine synapse density and spinophilin expression. As a consequence, our data suggest that cyclic fluctuations in spine synapse density result from pulsative release of GnRH from the hypothalamus and its effect on hippocampal estradiol synthesis, rather than from varying levels of serum estradiol. This hypothesis is further supported by higher GnRH receptor (GnRH-R) density in the hippocampus than in the cortex and hypothalamus and the specificity of estrus cyclicity of spinogenesis in the hippocampus, as compared to the cortex.

Original languageEnglish (US)
Pages (from-to)1417-1425
Number of pages9
JournalJournal of Neural Transmission
Volume116
Issue number11
DOIs
StatePublished - Nov 2009

Fingerprint

Estrus
Periodicity
Estradiol
Aromatase
Spine
Gonadotropin-Releasing Hormone
Synapses
Hypothalamus
Hippocampus
LHRH Receptors
Aromatase Inhibitors
Long-Term Potentiation
Dendrites
Serum
Steroids
Neurons

Keywords

  • Estradiol synthesis
  • Estrus cycle
  • GnRH
  • Spinogenesis

ASJC Scopus subject areas

  • Biological Psychiatry
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health

Cite this

Estrus cyclicity of spinogenesis : Underlying mechanisms. / Prange-Kiel, Janine; Fester, Lars; Zhou, Lepu; Jarry, Hubertus; Rune, Gabriele M.

In: Journal of Neural Transmission, Vol. 116, No. 11, 11.2009, p. 1417-1425.

Research output: Contribution to journalArticle

Prange-Kiel, Janine ; Fester, Lars ; Zhou, Lepu ; Jarry, Hubertus ; Rune, Gabriele M. / Estrus cyclicity of spinogenesis : Underlying mechanisms. In: Journal of Neural Transmission. 2009 ; Vol. 116, No. 11. pp. 1417-1425.
@article{ce2e739ad3bb418cb44e78179d5cc878,
title = "Estrus cyclicity of spinogenesis: Underlying mechanisms",
abstract = "Hippocampal spine density varies with the estrus cycle. The cyclic change in estradiol levels in serum was hypothesized to underlie this phenomenon, since treatment of ovariectomized animals with estradiol induced an increase in spine density in hippocampal dendrites of rats, as compared to ovariectomized controls. In contrast, application of estradiol to hippocampal slice cultures did not promote spinogenesis. In addressing this discrepancy, we found that hippocampal neurons themselves are capable of synthesizing estradiol de novo. Estradiol synthesis can be suppressed by aromatase inhibitors and by knock-down of Steroid Acute Regulatory Protein (StAR) and enhanced by substrates of steroidogenesis. Expression of estrogen receptors (ERs) and synaptic proteins, synaptogenesis, and long-term potentiation (LTP) correlated positively with aromatase activity in hippocampal cultures without any difference between genders. All effects due to inhibition of aromatase activity were rescued by application of estradiol to the cultures. Most importantly, gonadotropin- releasing hormone (GnRH) increased estradiol synthesis dose-dependently via an aromatase-mediated mechanism and consistently increased spine synapse density and spinophilin expression. As a consequence, our data suggest that cyclic fluctuations in spine synapse density result from pulsative release of GnRH from the hypothalamus and its effect on hippocampal estradiol synthesis, rather than from varying levels of serum estradiol. This hypothesis is further supported by higher GnRH receptor (GnRH-R) density in the hippocampus than in the cortex and hypothalamus and the specificity of estrus cyclicity of spinogenesis in the hippocampus, as compared to the cortex.",
keywords = "Estradiol synthesis, Estrus cycle, GnRH, Spinogenesis",
author = "Janine Prange-Kiel and Lars Fester and Lepu Zhou and Hubertus Jarry and Rune, {Gabriele M.}",
year = "2009",
month = "11",
doi = "10.1007/s00702-009-0294-x",
language = "English (US)",
volume = "116",
pages = "1417--1425",
journal = "Journal of Neural Transmission",
issn = "0300-9564",
publisher = "Springer Verlag",
number = "11",

}

TY - JOUR

T1 - Estrus cyclicity of spinogenesis

T2 - Underlying mechanisms

AU - Prange-Kiel, Janine

AU - Fester, Lars

AU - Zhou, Lepu

AU - Jarry, Hubertus

AU - Rune, Gabriele M.

PY - 2009/11

Y1 - 2009/11

N2 - Hippocampal spine density varies with the estrus cycle. The cyclic change in estradiol levels in serum was hypothesized to underlie this phenomenon, since treatment of ovariectomized animals with estradiol induced an increase in spine density in hippocampal dendrites of rats, as compared to ovariectomized controls. In contrast, application of estradiol to hippocampal slice cultures did not promote spinogenesis. In addressing this discrepancy, we found that hippocampal neurons themselves are capable of synthesizing estradiol de novo. Estradiol synthesis can be suppressed by aromatase inhibitors and by knock-down of Steroid Acute Regulatory Protein (StAR) and enhanced by substrates of steroidogenesis. Expression of estrogen receptors (ERs) and synaptic proteins, synaptogenesis, and long-term potentiation (LTP) correlated positively with aromatase activity in hippocampal cultures without any difference between genders. All effects due to inhibition of aromatase activity were rescued by application of estradiol to the cultures. Most importantly, gonadotropin- releasing hormone (GnRH) increased estradiol synthesis dose-dependently via an aromatase-mediated mechanism and consistently increased spine synapse density and spinophilin expression. As a consequence, our data suggest that cyclic fluctuations in spine synapse density result from pulsative release of GnRH from the hypothalamus and its effect on hippocampal estradiol synthesis, rather than from varying levels of serum estradiol. This hypothesis is further supported by higher GnRH receptor (GnRH-R) density in the hippocampus than in the cortex and hypothalamus and the specificity of estrus cyclicity of spinogenesis in the hippocampus, as compared to the cortex.

AB - Hippocampal spine density varies with the estrus cycle. The cyclic change in estradiol levels in serum was hypothesized to underlie this phenomenon, since treatment of ovariectomized animals with estradiol induced an increase in spine density in hippocampal dendrites of rats, as compared to ovariectomized controls. In contrast, application of estradiol to hippocampal slice cultures did not promote spinogenesis. In addressing this discrepancy, we found that hippocampal neurons themselves are capable of synthesizing estradiol de novo. Estradiol synthesis can be suppressed by aromatase inhibitors and by knock-down of Steroid Acute Regulatory Protein (StAR) and enhanced by substrates of steroidogenesis. Expression of estrogen receptors (ERs) and synaptic proteins, synaptogenesis, and long-term potentiation (LTP) correlated positively with aromatase activity in hippocampal cultures without any difference between genders. All effects due to inhibition of aromatase activity were rescued by application of estradiol to the cultures. Most importantly, gonadotropin- releasing hormone (GnRH) increased estradiol synthesis dose-dependently via an aromatase-mediated mechanism and consistently increased spine synapse density and spinophilin expression. As a consequence, our data suggest that cyclic fluctuations in spine synapse density result from pulsative release of GnRH from the hypothalamus and its effect on hippocampal estradiol synthesis, rather than from varying levels of serum estradiol. This hypothesis is further supported by higher GnRH receptor (GnRH-R) density in the hippocampus than in the cortex and hypothalamus and the specificity of estrus cyclicity of spinogenesis in the hippocampus, as compared to the cortex.

KW - Estradiol synthesis

KW - Estrus cycle

KW - GnRH

KW - Spinogenesis

UR - http://www.scopus.com/inward/record.url?scp=70449520113&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70449520113&partnerID=8YFLogxK

U2 - 10.1007/s00702-009-0294-x

DO - 10.1007/s00702-009-0294-x

M3 - Article

C2 - 19730783

AN - SCOPUS:70449520113

VL - 116

SP - 1417

EP - 1425

JO - Journal of Neural Transmission

JF - Journal of Neural Transmission

SN - 0300-9564

IS - 11

ER -