HYBRIDIZATION HISTOCHEMICAL-LOCALIZATION OF ACTIVIN RECEPTOR SUBTYPESIN RAT-BRAIN, PITUITARY, OVARY, AND TESTIS

We have studied the distribution of activin receptor gene expression i n the brain, pituitary, ovary, and testis of the adult rat by in situ hybridization, using probes complementary to the mRNAs encoding the mo use activin receptor subtypes II and IIB (ActRII and ActRIIB). Through out the brain, ActRII mRNA expression was stronger than that of ActRII B, and the patterns of expression were similar, although not identical . The most intense sites of activin receptor gene expression were the hippocampal formation, especially the dentate gyrus (ActRII), taenia t ecta, and induseum griseum; the amygdala, particularly the amygdaloid- hippocampal transition zone; and throughout the cortical mantle, inclu ding the primary olfactory cortex (piriform cortex and olfactory tuber cle); other regions of the cortex showing lesser degrees of hybridizat ion included the cingulate cortex, claustrum, entorhinal cortex, and s ubiculum. In addition, moderate levels of expression were observed in several hypothalamic areas involved in neuroendocrine regulation, such as the suprachiasmatic, supraoptic, paraventricular, and arcuate nucl ei. Moreover, activin receptors were also expressed in regions with in puts to the hypothalamus, both in the forebrain (bed nucleus of the st ria terminalis and medial preoptic area) and within the brainstem (nuc leus of the solitary tract, dorsal motor nucleus of the vagus, locus c oeruleus, and mesencephalic raphe system). ActRII mRNA was observed in the intermediate lobe of the pituitary and, less prominently, in the anterior lobe, whereas ActRIIB appeared to be weakly expressed through out all three pituitary divisions. In both male and female gonads, act ivin receptor message was clearly present in germ cells, and ActRII wa s the predominant form. In the ovary, in addition to an intense signal in the oocyte, activin receptor was expressed in corpus luteum and gr anulosa cells during diestrous day 1. In the testis, there was a stron g ActRII signal in rounded spermatids, and a moderate signal in pachyt ene spermatocytes. In contrast, ActRIIB was absent within tubules, but weakly expressed in interstitial and Leydig cells. This is the first report of the distribution of activin receptor message in adult mammal ian tissues. Although consistent with some previously suggested functi onal associations of activin-containing pathways in the brain, this pa ttern of expression suggests a greater role for activin than was previ ously appreciated in cortical, limbic, and somatosensory pathways and in the maturation of germ cells in the gonads of both male and female rats.