title: Effects of androgen and leptin on behavioral and cellular responses in female rats.
abstract: The causes of anxiety and depression in women with polycystic ovary syndrome (PCOS) remain elusive. To identify steps linking androgen signaling to the regulation of affective symptoms in vivo, we compared behavioral responses in female rats continuously exposed to DHT from puberty (a model of DHT-induced PCOS) and in rats exposed to DHT for 1week. Continuous and 1week of DHT exposure resulted in a general decrease in locomotor activity and time spent on the open arms in the elevated plus maze, indicating anxiety-like behavior. Rats with DHT-induced PCOS have increases in adiposity and circulating leptin levels accompanied by leptin resistance. One week of DHT exposure decreased androgen receptor (AR) expression in the hypothalamus and leptin synthesis and function in adipocytes; it also inhibited signal transducer and activator of transcription 3 (STAT3) and attenuated leptin activity by increasing levels of soluble leptin receptor, a leptin-binding protein, in the hypothalamus. This may affect the androgen-induced anxiety-related behavior in female rats. In conclusion, our results highlight the central role of androgens in behavioral function in female rats and suggest that androgens directly regulate the AR by decreasing its hypothalamic expression. Androgens also increase leptin synthesis in adipocytes, which drives central leptin signaling, and may regulate anxiety-related behaviors. Elucidating mechanisms by which androgens modulate female anxiety-like behavior may uncover useful approaches for treating women with PCOS who have symptoms of anxiety.
authors.affiliation: Institute of Neuroscience and Physiology, Department of Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Yi
authors.initials: Y
authors.lastname: Feng
authors.forename: Ruijin
authors.initials: R
authors.lastname: Shao
authors.forename: Birgitta
authors.initials: B
authors.lastname: Weijdegård
authors.forename: Tienpei
authors.initials: T
authors.lastname: Wang
authors.forename: Julia
authors.initials: J
authors.lastname: Johansson
authors.forename: Shan
authors.initials: S
authors.lastname: Sun
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Emil
authors.initials: E
authors.lastname: Egecioglu
authors.forename: Håkan
authors.initials: H
authors.lastname: Billig
authors.forename: Elisabet
authors.initials: E
authors.lastname: Stener-Victorin
mesh_terms: D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002468:Cell Physiological Phenomena / Q000187:drug effects*; D013196:Dihydrotestosterone; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D020738:Leptin / Q000494:pharmacology*; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D009929:Organ Size / Q000187:drug effects; D011085:Polycystic Ovary Syndrome / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology / Q000523:psychology; D051381:Rats; D017208:Rats, Wistar; D011944:Receptors, Androgen
chemical_list: D000728:Androgens; D020738:Leptin; D011944:Receptors, Androgen; D013196:Dihydrotestosterone