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

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‐β 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. © 2003 Wiley Periodicals, Inc. J Neurobiol 58: 493–502, 2004