Region-specific mechanisms for testosterone-induced Fos in hamster brain

Abstract

Hamsters self-administer androgens. Previously, we determined that testosterone (T) activates select steroid-and opiate-sensitive brain regions. Is T-stimulated neuronal activation androgenic? 35 castrated males with physiologic T replacement (n=7/group) were pre-treated with the androgen antagonist flutamide (15 mg/kg sc) or ethanol (0.25 ml), and infused into the lateral ventricle (ICV) for 4h with 40 μg T (TF and TE, respectively) or 40 μl vehicle (VF and VE). To determine if androgens and opiates activate overlapping brain areas, 7 additional males received 20 μg morphine sulfate ICV following ethanol injection (ME). Immediately after ICV infusion, animals were perfused. 60 μm coronal brain slices were stained for Fos. Fos-positive neurons were counted in a 0.3 mm 2 area from 5 regions previously shown to express T-induced Fos: the posteromedial bed nucleus of the stria terminalis (BSTPM), posteromedial amygdala (MeP), lateral habenula (LHb), ventral tegmental area, and lateral pontine nucleus. T induced Fos in all areas reported previously (TE vs. VE, p<0.05), except LHb (p>0.05). Morphine induced Fos in all 5 brain regions (ME vs. VE, p<0.05), indicating that androgens and opiates activate overlapping brain regions. Flutamide alone did not induce Fos (VF vs. VE, p>0.05). Moreover, flutamide treatment blocked T-induced Fos expression only in the steroid-sensitive BSTPM, suggesting that androgens mediate neuronal activation in this area (mean ±SEM: TF: 68.4±13.2 vs. TE: 137.9±17.6, p<0.05). The absence of flutamide effects on T-induced Fos in the steroid-sensitive MeP (TE: 210.6±50.0 vs. TF: 215.3±28.2, p>0.05) suggests that distinct mechanisms activate Fos in individual androgen-responsive nuclei.

c‐fos down‐regulation inhibits testosterone‐dependent male sexual behavior and the associated learning

“…It should be noted that the birds had already been treated with exogenous testosterone for 2 weeks when behavior testing was initiated. Several studies have previously demonstrated that the administration of testosterone (or of its metabolite estradiol) increases c‐fos expression the brain including the MPOA in the absence of any other stimulation (Insel, ; Dimeo & Wood, ; Nagypal & Wood, ) and a similar increase after estradiol treatment has been observed in peripheral tissues (rat arteries: Eyster et al ., ). Treatment with sex steroids is known to induce the expression of a variety of genes that ultimately result in changes in neural activity that will support the expression of sexual behavior.…”

Effects of season, testosterone and female exposure on c-fos expression in the preoptic area and amygdala of male green anoles

“…This conclusion may appear to contradict other studies, however, for example those in which immediate early gene expression can be enhanced with T treatment in birds Riters, 2005, 2006) or in rodents in which increases in c-fos expression can be directly attributed to T or estradiol exposure (e.g., Cattaneo and Maggi, 1990;Insel, 1990;Nagypal and Wood, 2007). It will be important in the future to more fully characterize the phenotype of the steroidresponsive cells, as well as to investigate additional mechanisms across these vertebrate groups, such as co-activators, which affect the manner in which particular cells respond to steroid signals (MacLean et al, 1997;O'Bryant and Jordan, 2005).…”

Effects of testosterone and estradiol on anxiety and depressive-like behavior via a non-genomic pathway

“…Thus, in some sense, the presence of c-Fos represents a genomic response to stimulation by sex steroids such as testosterone [41] . Kovacs and Sawchenko reported the highest c-Fos expression between 1 and 2 h after stimulation [42] , which suggests that 30 min after steroid application is not sufficient time for quantification of the effect of steroids on the number of c-Fos-positive cells.…”