Regulation of Motoneuronal Calcitonin Gene

The course of rnammalian sexual differentiation is largely under the control of the principal male gonadal steroid, the androgen testosterone. Despite the importance of androgens in the rnediation of sexual differentiation, the molecular basis of androgenic activity in the central nervous system remains poorly characterized. Calcitonin gene-related peptide (CGRP) has previously been reported to be regulated by testosterone in the Spinal Nucleus of the Bulbocavernosus (SNB) . The locus of androgenic regulation of CGRP expression within SNB motoneurons remains unclear, as the SNE3 is a component of a highly androgen sensitive neuromuscular circuit, with multiple possible targets for androgenic action . The present research utilizes a mosaic paradigm to test the hypothesis that the intracellular androgen receptor of SNB motoneurons regulates CGRP expression directiy in this cell population . Females heterozygous for the testicular feminization (tfm) androgen receptor mutation were androgenized perinatally to rescue the SNB and were implanted at sixty days with silastic capsules containing testosterone or nothing . Previous work has estabfished that this method yields females with -iiiapproximately half of the population of SNB motoneurons expressing functional androgen receptors . The remaining SNB motoneurons express non functional androgen receptors . This cellular mosaic of androgen receptors within the SNB allows for celiular analysis of androgen receptor activity in this neuronal population . Mosaic females were sacrificed six to eight weeks following implantation and spinal sections containing SNB motoneurons were immunolabeled simultaneously for CGRP and androgen receptor . Testosterone was found to decrease the proportion of CGRP immunoreactive SN6 motoneurons only in cells immunolabeled for functional androgen receptor . This finding clearly demonstrates the necessity of functional androgen receptor in SNB motoneurons for androgenic regulation of CGRP . The absence of an effect for !estosterone on cells not immunoreactive for androgen receptor challenges rnodels of androgenic regulation of CGRP within the SNB based on retrograde influence of the SNB target muscles . The current report constitutes, to the best of my knowledge, the first unambiguous in vivo denionstration of the necessity of a steroid receptor for steroid induced alterations in gene expression in a defined cell population .