Behavioral effects of 3 alpha-androstanediol .1. Modulation of sexual receptivity and promotion of GABA-stimulated chloride flux
Behavioral effects of 3 alpha-androstanediol .1. Modulation of sexual receptivity and promotion of GABA-stimulated chloride flux
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DOI：
10.1016/0166-4328(96)00004-6
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发表时间：
1996-09-01
影响因子：
2.7
通讯作者：
Erskine, MS
中科院分区：
文献类型：
--
作者：
Frye, CA;VanKeuren, KR;Erskine, MS
孕烷类神经甾体不仅可以通过作用于细胞内受体，还可以通过影响γ-氨基丁酸（GABA）受体复合物（GBR）来启动性感受性。研究雄性神经类固醇5 α-雄甾烷-3 α，17 β-二醇是否介导GBR作用（3 α-雄甾烷; 3 α-二醇）可能影响性行为的表达，卵巢切除（OVX）大鼠每天注射3 α-二醇（0.6、3.0、6.0和7.5 mg/kg）或媒介物（10%（v/v）乙醇的丙二醇溶液），以及s.c.在13.00 h和19.00 h注射雌二醇-17 β（E（2）：1 μ g/0.2 ml，溶于10%乙醇）。预后（P：0.5、1.0、2.0和4.0 mg/kg）或芝麻油溶剂。在Expt.在第一次注射3 α-二醇后18.00-19.00 h、56-57 h和注射P或赋形剂后4 h测量性感受性水平。3 α-雄甾烷二醇（6.0 mg/kg）在0.0、1.0、2.0和4.0 mg/kg P后减弱性行为（脊柱前凸商、脊柱前凸评级）并促进攻击/排斥行为。最高剂量的3 α-二醇（7.5 mg/kg）在0.0、1.0、2.0和4.0 mg/kg P后促进性行为并抑制攻击行为。在实验中。2，GABA刺激的氯离子通量在接受与抑制感受性相关的激素治疗（E（2）+P+3 α-Diol 3.0 mg/kg）的动物的皮质突触神经体中大于接受促进感受性的治疗（E（2）+P和E（2）+P+3 α-Diol 7.5 mg/kg）或非接受性ovx动物。在Expt. 3，由0.0、3.0和7.5 mg/kg s.c.通过放射免疫测定法测量给予E（2）和P致敏动物的剂量。在完成行为测试时，3 α-二醇的循环水平与先前在发情周期中确定的水平相当。这些数据表明，3 α-二醇影响E（2）和P-诱导的感受性的表达，并表明3 α-二醇，像其他神经甾体，可能发挥其对性行为的作用在GBR。
Pregnane neurosteroids may initiate sexual receptivity not only via actions at intracellular receptors, but by affecting gamma-aminobutyric acid (GABA) receptor complexes (GBRs). To investigate whether GBR-mediated actions of an androgenic neurosteroid 5 alpha-androstane-3 alpha,17 beta-diol (3 alpha-androstanediol; 3 alpha-Diol) may influence the expression of sexual behavior, ovariectomized (ovx) rats received daily injections of 3 alpha-Diol (0.6, 3.0, 6.0 and 7.5 mg/kg) or vehicle (10% (v/v) ethanol in propylene glycol) at 10.00 h, and s.c. injections of estradiol-17 beta (E(2): 1 mu g/0.2 ml in 10% ethanol) at 13.00 h and 19.00 h. Progesterone (P: 0.5, 1.0, 2.0 and 4.0 mg/kg) or sesame-oil vehicle was given at 12.30 h on the day following two days of 3 alpha-Diol and E(2) treatment. In Expt. 1, levels of sexual receptivity were measured at 18.00-19.00 h, 56-57 h after the first injection of 3 alpha-Diol and 4 h after P or vehicle injection. 3 alpha-Androstanediol (6.0 mg/kg) attenuated sexual behavior (lordosis quotient, lordosis rating) and facilitated aggressive/rejection behaviors following 0.0, 1.0, 2.0 and 4.0 mg/kg P. The highest dosage of 3 alpha-Diol (7.5 mg/kg) facilitated sexual behavior and inhibited aggression behaviors following 0.0, 1.0, 2.0 and 4.0 mg/kg P. In Expt. 2, GABA-stimulated chloride flux was greater in cortical synaptoneurosomes of animals that received hormone treatments associated with inhibited receptivity (E(2)+P+3 alpha-Diol 3.0 mg/kg) than following treatments that facilitated receptivity (E(2)+P and E(2)+P+3 alpha-Diol 7.5 mg/kg) or unreceptive ovx animals. In Expt. 3, circulating concentrations of 3 alpha-Diol resulting from the 0.0, 3.0 and 7.5 mg/kg s.c. doses administered to E(2)- and P-primed animals was measured by radioimmunoassay. Circulating levels of 3 alpha-Diol at the completion of behavioral testing were comparable to those previously ascertained across the estrous cycle. These data indicate that 3 alpha-Diol influences the expression of E(2) and P-induced receptivity, and suggest that 3 alpha-Diol, like other neurosteroids, may exert its effects on sexual behavior by actions at GBRs.