title: Prenatal administration of letrozole reduces SDN and SCN volume and cell number independent of partner preference in the male rat.
abstract: During development, the exposure to testosterone, and its conversion to estradiol by an enzyme complex termed aromatase, appears to be essential in adult male rats for the expression of typical male sexual behavior and female-sex preference. Some hypothalamic areas are the supposed neural bases of sexual preference/orientation; for example, male-oriented rams have a reduced volume of the sexually dimorphic nucleus (oSDN), while in homosexual men this nucleus does not differ from that of heterosexual men. In contrast, homosexual men showed a larger number of vasopressinergic cells in the suprachiasmatic nucleus (SCN). Interestingly, male rats perinatally treated with an aromatase inhibitor, 1,4,6-androstatriene-3,17-dione (ATD), also showed bisexual preference and an increased number of vasopressinergic neurons in the SCN. However, this steroidal aromatase inhibitor has affinity for all three steroid receptors. Recently, we reported that the prenatal administration of the selective aromatase inhibitor, letrozole, produced a subpopulation of males with same-sex preference. The aim of this study was to compare the volume and number of cells of the SDN and SCN (the latter nucleus was immunohistochemically stained for vasopressin) between males treated with letrozole with same-sex preference, males treated with letrozole with female preference and control males with female preference. Results showed that all males prenatally treated with letrozole have a reduced volume and estimated cell number in the SDN and SCN, independent of their partner preference. These results indicate that the changes in these brain areas are not related to sexual preference, but rather to the effects of letrozole. The divergent results may be explained by species differences as well as by the critical windows during which the aromatase inhibitor was administered.
authors.affiliation: Departamento de Farmacobiología, Centro de Investigación y Estudios Avanzados del Instituto Politécnico Nacional, Mexico.
authors.forename: Sandra
authors.initials: S
authors.lastname: Olvera-Hernández
authors.affiliation: Unidad de Microscopía, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico.
authors.forename: Miguel
authors.initials: M
authors.lastname: Tapia-Rodríguez
authors.affiliation: Netherlands Institute for Neuroscience, The Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands.
authors.forename: Dick F
authors.initials: DF
authors.lastname: Swaab
authors.affiliation: Departamento de Farmacobiología, Centro de Investigación y Estudios Avanzados del Instituto Politécnico Nacional, Mexico. Electronic address: jfernand@cinvestav.mx.
authors.forename: Alonso
authors.initials: A
authors.lastname: Fernández-Guasti
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D002452:Cell Count; D005260:Female; D000077289:Letrozole; D008297:Male; D052586:Mating Preference, Animal / Q000187:drug effects*; D009570:Nitriles / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D011301:Preoptic Area / Q000187:drug effects*; D051381:Rats; D012733:Sex Differentiation; D012747:Sexual Partners; D013493:Suprachiasmatic Nucleus / Q000187:drug effects*; D014230:Triazoles / Q000633:toxicity*; D014667:Vasopressins / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D009570:Nitriles; D014230:Triazoles; D014667:Vasopressins; D000077289:Letrozole
keywords: Letrozole; Partner preference; Sexually dimorphic nucleus; Suprachiasmatic nucleus; Vasopressin immunohistochemistry