title: Amyloid beta precursor protein regulates male sexual behavior.
abstract: Sexual behavior is variable between individuals, ranging from celibacy to sexual addictions. Within normal populations of individual men, ranging from young to middle aged, testosterone levels do not correlate with libido. To study the genetic mechanisms that contribute to individual differences in male sexual behavior, we used hybrid B6D2F1 male mice, which are a cross between two common inbred strains (C57BL/6J and DBA/2J). Unlike most laboratory rodent species in which male sexual behavior is highly dependent upon gonadal steroids, sexual behavior in a large proportion of these hybrid male mice after castration is independent of gonadal steroid hormones and their receptors; thus, we have the ability to discover novel genes involved in this behavior. Gene expression arrays, validation of gene candidates, and transgenic mice that overexpress one of the genes of interest were used to reveal genes involved in maintenance of male sexual behavior. Several genes related to neuroprotection and neurodegeneration were differentially expressed in the hypothalamus of males that continued to mate after castration. Male mice overexpressing the human form of one of these candidate genes, amyloid beta precursor protein (APP), displayed enhanced sexual behavior before castration and maintained sexual activity for a longer duration after castration compared with controls. Our results reveal a novel and unexpected relationship between APP and male sexual behavior. We speculate that declining APP during normal aging in males may contribute to the loss of sexual function.
authors.affiliation: Department of Biochemistry and Molecular Genetics, and Neuroscience Graduate Program, University of Virginia School of Medicine, Charlottesville, VA 22908, USA. JinHo.Park@umb.edu
authors.forename: Jin Ho
authors.initials: JH
authors.lastname: Park
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Bonthius
authors.forename: Houng-Wei
authors.initials: HW
authors.lastname: Tsai
authors.forename: Stefan
authors.initials: S
authors.lastname: Bekiranov
authors.forename: Emilie F
authors.initials: EF
authors.lastname: Rissman
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D009919:Orchiectomy / Q000379:methods; D011301:Preoptic Area / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012686:Septal Nuclei / Q000378:metabolism; D012726:Sexual Behavior, Animal / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D016564:Amyloid beta-Protein Precursor; D012333:RNA, Messenger