A sexually dimorphic distribution pattern of the novel estrogen receptor G-protein-coupled receptor 30 in some brain areas of the hamster Marcello Canonaco 1 , Giuseppina Giusi 1 , Antonio Madeo 2 , Rosa Maria Facciolo 1 , Rosamaria Lappano 2 , Alessia Canonaco 3 and Marcello Maggiolini 2 1 Comparative Neuroanatomy and Cytology Laboratory and 2 Pharmaco-Biology Department, University of Calabria, 87030 Arcavacata di Rende, Cosenza, Italy 3 Dermatology Department, ‘La Sapienza’ University of Rome, Piazza Aldo Moro, 00166 Rome, Italy (Correspondence should be addressed to M Canonaco; Email: canonaco@unical.it) Abstract The isolation of the G-protein-coupled receptor 30 (GPR30), an orphan membrane receptor unrelated to nuclear estrogen receptors (ERs), has become a key factor towards the unraveling of rapid estrogen action. This membrane receptor together with cellular signaling intermediaries, i.e., extracellular signal- dependent kinases 1 and 2, may promote neuronal proliferation and differentiation activities. In the present study, an evident gene expression pattern of GPR30 characterized postnatal 7 (young) and 60 (adult) days of age hamsters as shown by its heterogeneous mRNA distribution in hypothalamic, amygdalar and cerebellar areas of both sexes. In particular, most of the brain areas considered in the adult hamster plus only the amygdala and cerebellum of young animals behaved in a sexually dimorphic fashion. This similar pattern was also detected for the ERa and b, as shown by the latter receptor prevailing in young and adult females, while the former predominated in young females. Even for the two kinases, a sexually dimorphic distribution was featured above all for young hamsters. Overall, the findings of the present study established a distinct expression pattern of the novel ER (GPR30) that may operate differently in some brain areas of the hamster and this may provide interesting insights regarding its probable neuroprotective role during the execution of some hibernating states, which are typical of our rodent model. Journal of Endocrinology (2008) 196, 131–138 Introduction A plethora of evidence has demonstrated that estrogens are involved in many physiological processes in mammals, including developmental features, cellular homeostasis and neurobiological activities (Kow et al. 2005, Simpson et al. 2005) as well as pathological conditions (Maggiolini et al. 2004). Recently, in addition to the classical genomic mechanisms of action of intracellular estrogen receptor (ER) a and b, some studies have begun to emphasize the importance of a rapid non-genomic steroid action by the binding of 17b-estradiol (E 2 ) to a G-protein-coupled receptor 30 named GPR30. Although it is often straightforward to link the physiological effects of E 2 to a genomic model, considerable controversy still exists on its ability to elicit transcriptional responses independently of the classical nuclear receptor isoforms. On the basis of such observations, growing attention is beginning to be focused on some major health conditions such as tumor formations in which estrogen- dependent activities in the absence of ERs seem to predominately operate through GPR30 (Filardo & Thomas 2005). At the brain level, an elevated number of estrogen- dependent neuronal actions in areas such as hypothalamus (HTH), which is noted for its estrogen-enriched properties (McEwen 1991), seem to underlie GPR30 as a key factor for rapid cerebral estrogen actions (Canonaco et al. 2002). Recently, studies have pointed to the specific activity of GPR30 being tightly linked to some cellular signaling intermediaries, such as extracellular signal-related kinase (ERK) 1/2, since estrogens are able to induce their activities even in the absence of ERs (Sweatt 2004) and the inhibition of these factors by the rapid signaling cascades seems to decrease the potentiation of neuronal transcriptional activities (Vasudevan et al. 2005). Moreover, the aforementioned signaling intermediaries that seem to overlap the expression pattern of GPR30 throughout the brain have been reported to regulate neuronal proliferation, differentiation and postsynaptic processing. In this context, estrogen-induced neuronal signals seem to facilitate early ERK-dependent migration of brain elements and namely neurons and glia (Zsarnovszky & Belcher 2004). On the basis of these neuronal characteristics, it was our intention to evaluate the sexually dimorphic distribution pattern of GPR30 in some brain areas of young postnatal day 7 (PND7) and 60-day-old (PND60, adults) golden hamster (Mesocricetus auratus), a hibernating rodent. In addition, this pattern was correlated to that 131 Journal of Endocrinology (2008) 196, 131–138 DOI: 10.1677/JOE-07-0392 0022–0795/08/0196–131 q 2008 Society for Endocrinology Printed in Great Britain Online version via http://www.endocrinology-journals.org