Effects of androgen and leptin on behavioral and cellular responses in female rats.

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.

Spatiotemporal expression of androgen receptors in the female rat brain during the oestrous cycle and the impact of exogenous androgen administration: a comparison with gonadally intact males.

Little is known about the regulation and cellular distribution of androgen receptors (ARs) in female rodent brains at various stages of the oestrous cycle. This information is critical for further studies of androgen signalling in the regulation of brain function under physiological and pathophysiological conditions. In this report, we show that the distribution of AR immunoreactivity in the female rat brain is consistent with reported AR mRNA hybridisation signals in the male brain, except for the dentate gyrus of the hippocampus. Immunohistochemical and Western blot analyses performed herein revealed that the onset of region-specific changes in AR proteins was strongly correlated with circulating and ovarian levels of estradiol and testosterone across the oestrous cycle. During the metestrus and diestrus stages, however, the highest levels of AR expression were abolished by chronic dihydrotestosterone (DHT) treatment. This demonstrates that fluctuations in endogenous androgens are required for the regulation of AR expression in the female rat brain. Colocalisation studies revealed that: (1) anatomical variations in AR protein localisation existed between female and male brains, (2) AR immunoreactivity was both neuronal and non-neuronal, and (3) AR protein expression was lower in female rat brains at all stages of the oestrous cycle compared to age-matched males. Our results indicate the presence of regional sex differences in AR expression and changes in the proportion of AR between different subcellular compartments. Furthermore, DHT was found to down-regulate the level of AR in the subcellular compartment in females in a region-specific manner. As a whole, the present study provides the first step toward understanding the dynamics of AR expression and regulation in the brain during normal physiological conditions and for differences in neuronal androgen effects based on sex.

Electroacupuncture promotes insulin-like growth factors system in ovariectomized osteoporosis rats.

Postmenopausal Osteoporosis (PMOP) is induced by the deficiency of estrogen in postmenopausal women. Electroacupuncture (EA) has been confirmed to be effective in clinic. We adopted ovariectomized osteoporosis model of rats to observe the role of EA in PMOP. Fifty female SD rats were divided randomly into 5 groups: intact (INT, n = 10), sham operation (Sham, n = 10), model (n = 10), estrogen (E, n = 10) and electroacupuncture (EA, n = 10). The bone mineral content (BMC) and the bone mineral density (BMD) were examined in lumbar(1-6) and right thigh-bone, respectively, and estrodiol (E(2)), insulin-like growth factor I (IGF-I) and insulin-like growth factor binding proteins (IGF-BPs) were tested by RIA or ELISA. The results showed that BMC and BMD of lumbar 1-6 and right thigh-bone in PMOP model rats decreased markedly, while the level of serum E(2), IGF-I and IGF-BP1 were lower than in INT and Sham. However, EA could upgrade the contents of IGF-I and IGF-BP1 to increase BMD in PMOP rats, while no significant difference was seen in E group. Therefore, EA may promote IGF system to improve PMOP.