Role of female gonadal hormones in the CNS: clinical and experimental aspects.

The large body of evidence presented indicates that in the brain the action of sex hormones cannot be thought as restricted to the regulation of endocrine functions and mating behavior. Estrogens and progesterone seem to act in numerous regions of the CNS to regulate motor as well as limbic functions. Furthermore, the data reviewed indicate that these hormones may modulate neuronal activity through a wide variety of mechanisms. More studies should focus on such mechanisms in order to better understand the role of sex hormones in the CNS and to devise ways of limiting their effects on depression, epilepsy etc. It is known that in peripheral target organs these hormones modulate cell activities by binding to specific receptors which can recognize the DNA sequence and activate the transcription of selected genes (135, 136). There is evidence supporting the hypothesis that this mechanism of action has been conserved also in the brain. First, the brain receptors for progesterone and estrogens are functionally and biochemically indistinguishable from those in the periphery (4, 5): they may be concentrated in neuronal nuclei and bind chromatin "in vitro" (7). Second, a temporal relationship has been observed between administration of steroids and the increase of polymerase II activity (137) and protein synthesis (4, 5). Third, various hormone-induced behaviors may be blocked by inhibitors of the protein synthesis (138, 139, 140, 141). However, sex hormones must be capable to regulate neuronal functions by mechanisms other then genomic. In fact, the topical application of estrogen or progesterone on nervous tissue results in a rapid change of membrane potential (60, 71). Such a rapid effect is not likely to be the consequence of nuclear action, but rather must be related to events occurring on the cell surface. It has been hypothesized that sex steroids affect the fluidity of the cell membrane, therefore modifying the ion transport or neurotransmitter receptor activity (142). If this were the case we would expect to observe a similar effect after application of any steroid. Experimental evidence demonstrates that not all the steroids affect the nervous membrane potential. Moreover, two steroids, estradiol and progesterone, have been described to modulate membrane potential in an opposite way (66, 67, 69, 75). At the moment, there is no evidence for the presence of steroid receptors on neuronal membranes which could mediate the described phenomena.(ABSTRACT TRUNCATED AT 400 WORDS)