Masculine Sexual Behavior Is Disrupted in Male and Female Mice Lacking a Functional Estrogen Receptor α Gene

• Published in: Hormones and behavior Vol. 32; no. 3; pp. 176 - 183
• Main Authors: Wersinger, Scott R, Sannen, Koen, Villalba, Constanza, Lubahn, Dennis B, Rissman, Emilie F, De Vries, Geert J
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01-12-1997; Elsevier
• Subjects: Animals; Behavioral psychophysiology; Biological and medical sciences; Brain Chemistry - genetics; Brain Chemistry - physiology; Female; Fundamental and applied biological sciences. Psychology; Genotype; Hormones and behavior; Image Processing, Computer-Assisted; Immunohistochemistry; Male; Mice; Orchiectomy; Ovariectomy; Polymerase Chain Reaction; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Receptors, Androgen - deficiency; Receptors, Androgen - genetics; Receptors, Estrogen - deficiency; Receptors, Estrogen - genetics; Sex Characteristics; Sexual Behavior, Animal - physiology; Affect affectivity; Rodentia; Sexual behavior; Estrogen; Gene expression; Breeding behavior; Ovarian hormone; Vertebrata; Aromatization; Mammalia; Motivation; Mouse; Animal; Sex steroid hormone; Hormonal receptor
• ISSN: 0018-506X; 1095-6867
• DOI: 10.1006/hbeh.1997.1419

Masculine sexual behavior is regulated by testosterone (T). However, T can be metabolized to form estrogens or other androgens, which then activate their own receptors. We used knockout mice lacking a functional estrogen receptor α (ERα) gene to test the hypothesis that, following aromatization, T acts via the ERα to activate normal masculine sexual behavior. After gonadectomy and T replacement, wild-type (WT) male and female mice displayed masculine behavior. However, given the same T treatment, little masculine behavior was displayed by mice of either sex that lack a normal copy of the ERα gene. In particular, the latency to display masculine sex behavior and the number of mount attempts per trial were significantly reduced in the ERα−mice compared to WT littermates (P< 0.05). In addition, we found that in both sexes, ERα−mice have a smaller cluster of androgen receptor immunoreactivity in the bed nucleus of the stria terminalis. Using adult ERα−mice we were unable to determine whether these genotypic differences are due to organizational or activational effects. However, it is clear that the ERα plays a key role in the expression of masculine sexual behavior and in the regulation of androgen receptors in a neuronal cell population involved in the display of motivated behaviors.