Definition

The term "neurosteroid" was proposed in 1981. It applies to the steroids, the accumulation of which in the central and peripheral nervous systems occurs independently, at least in part, of supply by the steroidogenic endocrine glands, and which can be synthesized de novo in the nervous system from sterol precursors (9). All intermediary compounds can be assayed and/or demonstrated to be formed in situ. However in several instances, the precursor of a given neurosteroid, for example, progesterone in the case of 3a, 5a-TH PROG, can be synthesized in the nervous system but is also provided by endocrine sources (ovarian, adrenal, and/or placental). The physiological significance of neurosteroidal PROG is clearly different from that of endocrine PROG; it may act paracrinally (see Subheading "Trophic Effects of Neurosteroids on Neurons and Glial Cells") and in particular the site of formation of 3a, 5a-TH PROG might be different from either source. On the contrary, steroids that are formed exclusively from blood-borne precursors, as, for example, estrogens (estrone and estradiol), which derive by aromatization from blood-borne androstenedione and testosterone, will not be qualified as neurosteroids.

There is a tendency in the scientific literature to regard as neurosteroids all neuroac-tive steroids, including synthetic, nonnatural molecules. This is unfortunate. We shall restrict our study to steroids that are still present in the nervous system long after the removal of steroidogenic glands, and the biosynthesis of which can be demonstrated, by pathways that have been previously documented in endocrine glands, eventually by mechanisms proper to the nervous system. Alone, none of these two conditions suffices to qualify a steroid present in the nervous system as a neurosteroid.

MEASUREMENT The Rodent Brain

Brain samples from adult male rats of the Sprague Dawley strain (11-12 wk old) were generally used. Plasma and tissue homogenates were processed as previously described

Table 1

Neurosteroids in the Adult Male Rat Brain and Plasma

Table 1

Neurosteroids in the Adult Male Rat Brain and Plasma

0 0

Post a comment