Sep-Pak-prepurified brain tissue and homogenate extracts were analyzed by RP-HPLC as previously described [ 55 , 61 , 62 ] using a Gilson model 305 master pump acting as a system controller, a Gilson model 306 slave pump controlled by the previous pump, a Gilson model 115 variable wavelenght UV detector set at 240 nm (Gilson ., Villier-le-Bel, France) and a Rheodyne model 7125 injector (Rheodyne Inc, California). A X 30 cm Nova-Pak C 18 column (Waters Associates) equilibrated with 60% sol. A and 40% sol. B was used for analysis. Each dry extract was dissolved in 400 μl of a solution consisting of 60% sol. A and 40% sol. B, and the whole sample was injected at a flow rate of 1 ml/min. The radioactive steroids formed from [ 3 H]Δ 5 P were separated using a gradient of sol. B (40–100% over 104 min) including 4 isocratic steps at 40% (0–10 min), 64% (39–59 min), 80% (69–79 min) and 100% sol. B (94–104 min). Tritiated compounds eluted from the HPLC column were detected by using a flow scintillation analyzer (Radiomatic Flo-One\Beta A-500, Packard, Meridien, CT) and the radioactivity contained in each peak was integrated.
AB - Neuroactive steroids synthesized in neuronal tissue, referred to as neurosteroids, are implicated in proliferation, differentiation, activity and survival of nerve cells. Neurosteroids are also involved in the control of a number of behavioral, neuroendocrine and metabolic processes such as regulation of food intake, locomotor activity, sexual activity, aggressiveness, anxiety, depression, body temperature and blood pressure. In this article, we summarize the current knowledge regarding the existence, neuroanatomical distribution and biological activity of the enzymes responsible for the biosynthesis of neurosteroids in the brain of vertebrates, and we review the neuronal mechanisms that control the activity of these enzymes. The observation that the activity of key steroidogenic enzymes is finely tuned by various neurotransmitters and neuropeptides strongly suggests that some of the central effects of these neuromodulators may be mediated via the regulation of neurosteroid production.
Dutasteride was patented in 1996  and was first described in the scientific literature in 1997.  It was approved by the FDA for the treatment of BPH in November 2001 and was introduced into the United States market the following year under the brand name Avodart.  Dutasteride has subsequently been introduced in many other countries, including throughout Europe and South America .  The patent protection of dutasteride expired in November 2015 and the drug has since become available in the United States in a variety of low-cost generic formulations .