NEONATAL IMPRINTING PREDETERMINES THE SEXUALLY DIMORPHIC, ESTROGEN-DEPENDENT EXPRESSION OF GALANIN IN LUTEINIZING-HORMONE-RELEASING HORMONENEURONS

The incidence of colocalization of galanin (GAL) in luteinizing hormon e-releasing hormone (LHRH) neurons is 4- to 5-fold higher in female th an male rats. This fact and the finding that the degree of colocalizat ion parallels estradiol levels during the estrous cycle suggest that G AL is an estrogen-inducible product in a subset of LHRH neurons. To an alyze further this paradigm we evaluated the effects of gonadectomy an d steroid replacement therapy in male and female rats. Ovariectomy res ulted in a significant decrease in the number of cells colocalizing LH RH and GAL, whereas estradiol replacement to such animals restored the incidence of colocalization to that observed in controls. In males, h owever, estradiol treatment failed to enhance the incidence of colocal ization of GAL and LHRH, indicating, therefore, that the colocalizatio n of these peptides is gender-determined. This possibility-i.e., gende r-specific determination of LHRH neurons coexpressing GAL-was evaluate d by neonatal manipulation of hypothalamic steroid imprinting. As ment ioned above, male rats did not respond to estrogen or testosterone by increasing GAL/LHRH colocalization as females did. Neonatally orchidec tomized rats, whose hypothalami have not been exposed to testosterone during the critical period, when treated with estrogen in adulthood sh owed an increase in colocalization of GAL and LHRH similar to that see n in female animals. These observations indicate that the colocalizati on of LHRH/GAL is neonatally determined by an epigenetic mechanism tha t involves the testis. In summary, this sex difference in the incidenc e of colocalization of GAL and LHRH represents a unique aspect of sexu al differentiation in that only certain phenotypic characteristics of a certain cellular lineage are dimorphic. The subpopulation of LHRH ne urons that also produces GAL represents a portion of the LHRH neuronal system that is sexually differentiated and programed to integrate, un der steroidal control, a network of LHRH neurons that could synchroniz e their activity to control the estrous cycle in rats.