Ovarian steroids influence cell proliferation in the dentate gyrus of the adult female rat in a dose- and time-dependent manner

J Comp Neurol. 2005 Jan 17;481(3):252-65. doi: 10.1002/cne.20385.

Abstract

In previous work, we have demonstrated that cell proliferation in the adult hippocampal formation is regulated by estrogen under both natural and experimental conditions. To determine the extent to which this regulation is affected by the dose or schedule of hormone treatment, or progesterone administration, we examined the impact of different acute and chronic ovarian hormone replacement regimens on cell production using the S-phase marker bromodeoxyuridine. Additionally, we investigated the long-term impact of surgical ovarian hormone depletion on the capacity of estrogen to stimulate cell proliferation and the production of new cells that express either TuJ1 (a marker of neuronal phenotype) or glial fibrillary acidic protein (GFAP; a marker of astroglial phenotype). Acute treatment with a moderate, but not a low or a high, dose of estrogen rapidly increased cell proliferation in ovariectomized (OVX) animals, an effect that was reversed by the administration of progesterone. In contrast, OVX animals that were chronically replaced with either estrogen alone (continuous or cyclic) or estrogen plus progesterone (cyclic) did not exhibit an estrogen-induced increase in cell proliferation 3 weeks following the onset of hormone replacement. In animals that were subjected to a prolonged absence of ovarian hormones, acute treatment with the moderate dose of estrogen failed to stimulate cell proliferation, and a decrease in the number of new cells expressing a neuronal phenotype was evident. Collectively, these results indicate that a prolonged reduction in ovarian hormones results in 1) a diminished responsiveness to estrogen over time in this system and 2) a decrease in neuron production that is unlikely to be reversible by standard regimens of hormone replacement.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biomarkers
  • Cell Proliferation / drug effects*
  • Dentate Gyrus / cytology
  • Dentate Gyrus / drug effects*
  • Dentate Gyrus / metabolism
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Down-Regulation / physiology
  • Estrogen Receptor alpha / drug effects
  • Estrogen Receptor alpha / metabolism
  • Estrogen Receptor beta / drug effects
  • Estrogen Receptor beta / metabolism
  • Estrogens / metabolism
  • Estrogens / pharmacology
  • Estrous Cycle / metabolism*
  • Female
  • Gonadal Steroid Hormones / metabolism
  • Gonadal Steroid Hormones / pharmacology*
  • Histones / metabolism
  • Neurons / cytology
  • Neurons / drug effects*
  • Neurons / metabolism
  • Ovariectomy
  • Progesterone / metabolism
  • Progesterone / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Stem Cells / drug effects
  • Stem Cells / metabolism
  • Time Factors

Substances

  • Biomarkers
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Estrogens
  • Gonadal Steroid Hormones
  • Histones
  • Progesterone