title: Prostaglandin-E2: a point of divergence in estradiol-mediated sexual differentiation.
abstract: The preoptic area of the mammalian forebrain is a critical substrate for the development and maintenance of many sexually dimorphic behaviors relevant to reproduction. Normal development of the male rodent brain requires completion of two processes: (1) masculinization-induction of the male phenotype, and (2) defeminization-removal of the female phenotype. Both processes, although distinct, are largely directed by the same steroid, estradiol. Whether estradiol achieves both ends via the same or separate mechanisms has been unknown. Here, we report that prostaglandin-E(2) (PGE(2)) acting downstream of estradiol, is necessary and sufficient to masculinize sexual behavior but does not affect defeminization of sexual behavior or maternal behavior. Moreover, the volume of the sexually dimorphic nucleus of the preoptic area predicts defeminization of sexual behavior, but not masculinization of sexual behavior. Another sexually dimorphic cellular endpoint regulated by estradiol, spinophilin protein expression in the mediobasal hypothalamus, was not affected by PGE(2). Thus, PGE(2) is a key divergence point in the downstream actions of estradiol to simultaneously masculinize and defeminize sexual behavior.
authors.affiliation: Department of Physiology and Program in Neuroscience, University of Maryland School of Medicine, 655 W. Baltimore Street, Baltimore, MD 21201, USA. btodd@aecom.yu.edu
authors.forename: Brigitte J
authors.initials: BJ
authors.lastname: Todd
authors.forename: Jaclyn M
authors.initials: JM
authors.lastname: Schwarz
authors.forename: Margaret M
authors.initials: MM
authors.lastname: McCarthy
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D015153:Blotting, Western; D015232:Dinoprostone / Q000502:physiology*; D004958:Estradiol / Q000502:physiology*; D005260:Female; D005835:Genitalia / Q000033:anatomy & histology; D008297:Male; D008425:Maternal Behavior / Q000502:physiology; D011301:Preoptic Area / Q000254:growth & development / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D012733:Sex Differentiation / Q000187:drug effects / Q000502:physiology*; D012726:Sexual Behavior, Animal / Q000187:drug effects / Q000502:physiology
chemical_list: D004958:Estradiol; D015232:Dinoprostone