Effects of progesterone derivatives, dihydroprogesterone and tetrahydroprogesterone, on the subependymal layer of the adult rat

J Neurobiol. 2004 Mar;58(4):493-502. doi: 10.1002/neu.10290.

Abstract

Indirect evidence suggests that in the subependymal layer (SEL) steroid hormones could be partially involved in the modulation of neurogenesis, but little or nothing is known about a direct effect of these molecules on this cellular system. The possible effect of progesterone (P) and/or its neuroactive metabolites, dihydroprogesterone (DHP) and tetrahydroprogesterone (THP), on the two cellular components of the SEL (i.e., proliferating/migrating neuroblasts and protoplasmic astrocytes) has been analyzed in adult male rat. P, DHP, and THP were administered by intraventricular injections and after 2 days the SEL was analyzed by immunohistochemistry by using anti-glial fibrillary acidic protein (GFAP) and anti-vimentin antibodies, to label the glial compartment, anti-polysialylated form of the neural cell adhesion molecule (PSA-NCAM), anti-Stathmin, and anti-beta III Tubulin antibodies to label the migrating neuroblasts. Furthermore, the newly formed cells were identified by using intraventricular injections of 5-bromo-2'-deoxyuridine (BrdU) detected immunohistochemically. Our results demonstrate that DHP and THP treatments drastically decrease the number of BrdU-labeled cells within the SEL. THP, DHP, and to a lesser extent P, administrations also induce molecular and structural modifications of the SEL glial compartment. On the whole, the present results indicate that neuroactive derivatives of P (i.e., DHP and THP) exert direct effects on adult neurogenesis, strongly affecting both neuroblasts and astrocytes of the SEL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 20-alpha-Dihydroprogesterone / pharmacology*
  • Animals
  • Astrocytes / cytology
  • Astrocytes / drug effects
  • Cell Division / drug effects
  • Cell Division / physiology
  • Ependyma / cytology*
  • Ependyma / drug effects*
  • Male
  • Progesterone / analogs & derivatives*
  • Progesterone / pharmacology
  • Rats
  • Rats, Sprague-Dawley

Substances

  • 20-alpha-Dihydroprogesterone
  • Progesterone