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Sexually Dimorphic Effects of Testosterone on Preoptic Area Calcitonin Gene-Related Peptide mRNA Expression Depend upon Neuron Location and Differential Estrogen and Androgen Receptor Activation

Laboratory of Neuroendocrinology, The Babraham Institute, Cambridge, United Kingdom CB2 4AT

Address all correspondence and requests for reprints to: Dr. Allan E. Herbison, Laboratory of Neuroendocrinology, The Babraham Institute, Cambridge, United Kingdom CB2 4AT. E-mail address: allan.herbison{at}bbsrc.ac.uk

Experiments examined activational roles of gonadal steroids on the sexually dimorphic, calcitonin gene-related peptide-expressing neurons of the rat preoptic area. Gonadectomy of male rats followed by treatment with testosterone, dihydrotestosterone, or estrogen demonstrated that the tonic suppressive influence of testosterone on cellular levels of calcitonin gene-related peptide mRNA expression in the medial preoptic nucleus and anteroventral periventricular nucleus occurred through either ER- or AR-mediated mechanisms (P < 0.05). The gonadectomy of adult female rats demonstrated little tonic influence of ovarian steroids upon calcitonin gene-related peptide mRNA levels. However, the administration of male levels of testosterone to ovariectomized rats resulted in reduced calcitonin gene-related peptide mRNA expression within the medial preoptic nucleus (P < 0.05) and, strikingly, a 3-fold induction in calcitonin gene-related peptide mRNA expression in the anteroventral periventricular nucleus (P < 0.01). Testosterone’s effects in the medial preoptic nucleus and anteroventral periventricular nucleus of the female required both ER and AR activation. Dual labeling immunocytochemical studies revealed that less than 10% of calcitonin gene-related peptide neurons in the male expressed ARs compared with approximately 50% in the female. These investigations reveal that sexually differentiated region- and steroid receptor-specific mechanisms function in association with the sex differences in circulating gonadal steroids to maintain the sexually dimorphic nature of calcitonin gene-related peptide expression in the preoptic area of the adult rat.