Effect of Short‐and Long‐Term Gonadectomy on Neuroactive Steroid Levels in the Central and Peripheral Nervous System of Male and Female Rats

Abstract

Significant levels of neuroactive steroids are still detected in the nervous system of rodents after the removal of peripheral steroidogenic glands. However, the influence of the plasma levels of gonadal steroids on the levels of neuroactive steroids in the nervous system has not so far been clarified in detail. Accordingly, by liquid chromatography tandem mass spectrometry, we have analysed the levels of neuroactive steroids in the sciatic nerve, in three central nervous system (CNS) regions (i.e. cerebellum, cerebral cortex and spinal cord) and in the plasma of male and female animals. The levels present in gonadally intact animals were compared with those present in short- and long-term gonadectomised animals. We observed that: (i) changes in neuroactive steroid levels in the nervous system after gonadectomy do not necessarily reflect the changes in plasma levels; (ii) long-term gonadectomy induces changes in the levels of neuroactive steroids in the peripheral nervous system (PNS) and the CNS that, in some cases, are different to those induced by short-term gonadectomy; (iii) the effect of gonadectomy on neuroactive steroid levels is different between the PNS and the CNS and within different CNS regions; and (iv) the effects of gonadectomy on neuroactive steroid levels in the nervous system show sex differences. Altogether, these observations indicate that the nervous system adapts its local levels of neuroactive steroids in response to changes in gonadal hormones with sex and regional specificity and depending on the duration of the peripheral modifications.

New steps forward in the neuroactive steroid field

“…Furthermore, in agreement with the reported sex dimorphism in the expression of steroidogenic molecules in the CNS [24,25], the local differences in neuroactive steroid levels also depend on the sex [22,23]. For instance, females have higher levels of PREG, PROG and its derivatives in the sciatic nerve than males, while males have higher T and DHT levels in the sciatic nerve than females.…”

“…As recently demonstrated in rats by liquid chromatographytandem mass spectrometry (LC-MS/MS), the levels of neuroactive steroids are different in the nervous system vs plasma levels and vs cerebrospinal fluid (CSF), in CNS vs PNS and among the CNS structures so far considered [22,23]. Furthermore, in agreement with the reported sex dimorphism in the expression of steroidogenic molecules in the CNS [24,25], the local differences in neuroactive steroid levels also depend on the sex [22,23].…”

Modulation of synaptic plasticity in the hippocampus by hippocampus-derived estrogen and androgen

“…The presence of 17␤-E2, DHT and estrone (E1) had not yet been observed even by mass-spectrometric assay including gas chromatography with mass-spectrometry (GC-MS/MS), liquid chromatography with mass-spectrometry (LC-MS) and liquid chromatography with tandem-mass-spectrometry (LC-MS/MS), although DHEA and T have been observed in the whole brain extracts [89,90,94,97,98].…”

Dihydrotestosterone as a Protective Agent in Chronic Experimental Autoimmune Encephalomyelitis

“…In particular, DHT treatment was ineffective in castrated mice [23] , while it exerted beneficial effects in intact male EAE mice [16] . In this context, it is important to recall that, at least as reported in rats, the CNS adapts its local levels of neuroactive steroids in response to castration [47] . Consequently, the effects of neuroactive steroid treatment could be affected by this surgical manipulation.…”