Distribution and hormonal regulation of androgen receptor immunoreactivity in the forebrain of the male European ferret

Abstract

The distribution and hormonal regulation of androgen-receptor-immunoreactive (AR-ir) cells in the male European ferret forebrain were examined. AR-ir cells were found in many limbic and hypothalamic structures, and their distribution was similar to that reported for cells that either bind androgen or contain AR protein or mRNA in other species. Regulation of brain AR immunoreactivity by gonadal steroids was brain-region dependent. In most regions examined, including the preoptic area, amygdala, and several hypothalamic nuclei, castration reduced the density of AR-ir profiles and the intensity of immunocytochemical staining, and long-term (days) androgen, but not estrogen, replacement restored these parameters of AR immunoreactivity. Other areas, such as the bed nucleus of the stria terminalis, appeared to be relatively resistant to modulation of AR immunoreactivity by castration and long-term androgen treatment. The ability of testosterone to increase AR-ir profile density is not a simple consequence of translocation of AR from the cytoplasm to the nucleus, because short-term (hours) treatment with testosterone did not result in an increase in AR-ir profile density equivalent to that seen after 10 days of testosterone treatment. Thus, androgens appear to be able to increase AR levels within certain brain cell groups, thereby altering target tissue responsiveness to their own action.

Social status and sex independently influence androgen receptor expression in the eusocial naked mole-rat brain

“…As a rule, AR is found throughout the hypothalamus and preoptic area as well as in telencephalic structures that project to these regions. Indeed, AR is found in the same structures investigated here (BST, PVN, VMH, MeA, and PMv) in diverse mammalian species including (but not limited to) rats, mice, hamsters, ferrets, opossums, sheep, and humans (e.g., Clancy et al, 1994;Fernández-Guasti et al, 2000;Herbison et al, 1996;Iqbal et al, 1995;Kashon et al, 1996;Lu et al, 1998;Simerly et al, 1990;Wood and Newman, 1995). The BST, PVN, MeA, VMH, and PMv comprise key nodes of an interconnected neural circuit that regulates neuroendocrine function and couples the expression of reproductive behaviors with appropriate environmental stimuli.…”

“…Sparse labeling in the isocortex and CA2 and CA3 of the hippocampus appeared to be specific to pyramidal neurons. Interestingly, in contrast to sections from the mouse brain processed at the same time, and to previous published studies of AR distribution in other mammals (e.g., Commins and Yahr, 1985;Iqbal et al, 1995;Karatsoreos et al, 2007;Kashon et al, 1996;Simerly et al, 1990;Xiao and Jordan, 2002), naked mole-rats had remarkably little AR immunoreactivity in the suprachiasmatic nucleus (SCN) or CA1 of the hippocampus (Figure 3). …”

“…The relationship between androgens and AR expression is complex and differs depending on brain region and species. Nonetheless, testosterone restores AR immunoreactivity following castration in reproductive brain regions in rats (Sar et al, 1990), ferrets (Kashon et al, 1996), guinea pigs (Choate and Resko, 1996) and Siberian hamsters (Bittman et al, 2003). Plasma levels of androgens have not been reported for naked mole-rats, but males have higher urinary testosterone than females Faulkes, 1997, 1998;.…”

“…Androgens act via androgen receptors (AR), which are ligand-dependent transcription factors belonging to the superfamily of intracellular nuclear receptors (Prins, 2000). In other species, the AR is expressed in many of the brain regions involved in the control of sex-typical reproductive behaviors (e.g., Choate and Resko, 1992;Commins and Yahr, 1985;Kashon et al, 1996;Lu et al, 1998;Simerly et al, 1990;Wood and Newman, 1995). In addition, sex differences in the brain are organized and/or activated in adulthood by circulating testosterone acting via AR, or after conversion to an estrogen and binding to an estrogen receptor (ER), and both AR and ER are expressed in neural regions that are sexually dimorphic (e.g., Commins and Yahr, 1985;Simerly et al, 1990;Wood and Newman, 1995).…”

The regulation of neuroendocrine function: Timing is everything

“…Testosterone may act through SCN androgen receptors. To date, androgen receptors have been identified in the SCN of several species (Clancy et al, 1994;Fernandez-Guasti et al, 2000;Kashon et al, 1996;Michael and Rees, 1982;Rees and Michael, 1982). Alternatively, testosterone may exert its effects through conversion to estradiol, which may act either directly on receptors in the SCN (e.g., Shughrue et al, 1997), or indirectly in ER-expressing cells in other brain areas that, in turn, communicate with the SCN (de la Iglesia et al, 1999).…”