McIntyre K L, Porter D M, Henderson L P
Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA.
Neuropharmacology. 2002 Sep;43(4):634-45. doi: 10.1016/s0028-3908(02)00154-5.
Chronic exposure to anabolic androgenic steroids (AAS) has deleterious effects on reproductive health in both human and animal subjects. Neurotransmission mediated by the gamma-aminobutyric acid type A (GABA(A)) receptor in the medial amygdala (MeA), the medial preoptic area (mPOA), and the ventromedial nucleus (VMN) of the hypothalamus plays a critical role in mediating sexual behaviors. Here we used semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) to examine levels of alpha(1), alpha(2), alpha(5), gamma(1), gamma(2), and epsilon subunit mRNAs in these three regions of the brain. Our results demonstrate that chronic exposure to either a high or a moderate dose of the AAS, 17alpha-methyltestosterone (17alpha-MeT), significantly decreased the levels of specific alpha and gamma subunit mRNAs in a manner that depended on the dose of AAS and age and sex of the animals. Specifically, the moderate dose of AAS elicited significant changes only in pubertal females and the majority of changes observed in pubertal animals with the high dose also occurred in females. In contrast, the moderate dose of AAS induced no significant changes in adult mice of either sex, while the high dose had effects in both males and females. In addition to determining the effects of chronic AAS treatment, a developmental analysis of drug-naïve animals demonstrated that GABA(A) receptor subunit mRNA levels in these regions of the forebrain undergo significant changes as animals proceed through puberty. These data demonstrate that the effects of AAS exposure on GABA(A) receptor expression are superimposed upon dynamic developmental changes that accompany the transition from puberty to adulthood.
长期接触合成代谢雄激素类固醇（AAS）对人类和动物受试者的生殖健康均有有害影响。内侧杏仁核（MeA）、内侧视前区（mPOA）和下丘脑腹内侧核（VMN）中由A型γ-氨基丁酸（GABA(A)）受体介导的神经传递在介导性行为中起关键作用。在此，我们使用半定量逆转录-聚合酶链反应（RT-PCR）来检测大脑这三个区域中α(1)、α(2)、α(5)、γ(1)、γ(2)和ε亚基mRNA的水平。我们的结果表明，长期接触高剂量或中等剂量的AAS，即17α-甲基睾酮（17α-MeT），会以取决于AAS剂量以及动物年龄和性别的方式显著降低特定α和γ亚基mRNA的水平。具体而言，中等剂量的AAS仅在青春期雌性动物中引起显著变化，而在高剂量青春期动物中观察到的大多数变化也发生在雌性动物中。相比之下，中等剂量的AAS在成年雌雄小鼠中均未诱导出显著变化，而高剂量对雄性和雌性均有影响。除了确定长期AAS治疗的影响外，对未接触药物动物的发育分析表明，随着动物进入青春期，前脑这些区域的GABA(A)受体亚基mRNA水平会发生显著变化。这些数据表明，AAS暴露对GABA(A)受体表达的影响叠加在从青春期到成年期转变所伴随的动态发育变化之上。
