Maseroli Elisa, Santangelo Andrea, Lara-Fontes Beatriz, Quintana Gonzalo Renato, Mac Cionnaith Conall E, Casarrubea Maurizio, Ricca Valdo, Maggi Mario, Vignozzi Linda, Pfaus James G
Andrology, Women's Endocrinology and Gender Incongruence Unit, Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Viale Pieraccini 6, Florence 50139, Italy; Center for Studies in Behavioral Neurobiology, Department of Psychology, Concordia University, Montréal, QC H4B 1R6 Canada.
Psychiatry Unit, Department of Health Sciences. University of Florence, Italy; Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.). Human Physiology Section "Giuseppe Pagano", Corso Tukory 129, Palermo 90134, Italy.
Psychoneuroendocrinology. 2020 May;115:104606. doi: 10.1016/j.psyneuen.2020.104606. Epub 2020 Feb 7.
It is still unclear whether Testosterone (T) increases sexual desire through a stimulation of the androgen receptor in relevant brain regions or through its conversion to estrogens. The aim of this study was to clarify the mechanisms of T facilitation of female sexual desire by assessing the effect of a non-aromatizable androgen (Dihydrotestosterone, DHT) in a validated animal model. Ovariectomized (OVX) Long-Evans rats were treated with oil (O) + O, 10 mcg Estradiol Benzoate (EB) + O, 10 mcg EB + 500 mcg Progesterone (P), O + 500 mcg DHT or 10 mcg EB + 500 mcg DHT (n = 12 per group). EB was administered 48 h, while P and DHT 4 h, prior to 4 sexual behavioral testing sessions in bisected unilevel pacing chambers. Appetitive behaviors (the frequencies of hops/darts and solicitations) were considered as the main outcome measure. Sexual receptivity indexes [lordosis magnitude, expressed as lordosis rating (LR), and lordosis quotient (LQ)], rejection responses, as well as mounts, intromissions and ejaculations received from the male were also coded. The probability of transition among sexual behaviors was evaluated by Transition Matrices; T-Pattern analysis was performed to detect hidden repeated temporal behavioral sequences. Preliminary analyses found no statistically significant differences between the O + O and EB + O groups, therefore we excluded the EB + O group from further analyses. Rats treated with EB + DHT displayed significantly more appetitive behaviors compared to negative controls (O + O and O + DHT), whereas no difference was observed between EB + DHT rats and positive controls (EB + P); noteworthy, a higher number of appetitive behaviors was observed in the O + DHT group compared to the O + O group. Furthermore, rats treated with EB + DHT showed significantly higher receptivity measures (LR and LQ) and received more mounts, intromissions and ejaculations compared to negative controls (O + O and O + DHT), to levels equivalent to EB + P. No differences were detected in female-male mounts or rejection responses among the 4 groups. Under a qualitative perspective, full solicitation was found exclusively in T-patterns of the EB + DHT group, which was also the only one to display T-patterns of higher order encompassing appetitive behaviors-only events. In conclusion, the administration of DHT in EB-primed OVX Long-Evans rats enhances sexual behavior measures. Specifically, DHT seems to stimulate sequences of appetitive behaviors separated from copulative/reproductive measures. Our data support an independent role of androgens in the facilitation of female sexual desire.
睾酮（T）是通过刺激相关脑区的雄激素受体还是通过转化为雌激素来增加性欲，目前仍不清楚。本研究的目的是通过在一个经过验证的动物模型中评估一种不可芳香化的雄激素（双氢睾酮，DHT）的作用，来阐明T促进雌性性欲的机制。将去卵巢（OVX）的Long-Evans大鼠分为以下几组进行处理：油剂（O）+油剂（O）组、10微克苯甲酸雌二醇（EB）+油剂（O）组、10微克EB + 500微克孕酮（P）组、油剂（O）+ 500微克DHT组或10微克EB + 500微克DHT组（每组n = 12）。在二分单层起搏室进行4次性行为测试前48小时给予EB，P和DHT则在测试前4小时给予。将求偶行为（跳跃/突进和 solicitation 的频率）作为主要结局指标。还对性接受指数[弓背反射幅度，以弓背反射评分（LR）和弓背反射商（LQ）表示]、拒绝反应以及从雄性大鼠获得的爬跨、插入和射精进行编码。通过转移矩阵评估性行为之间转换的概率；进行T模式分析以检测隐藏的重复时间行为序列。初步分析发现油剂（O）+油剂（O）组和EB +油剂（O）组之间无统计学显著差异，因此我们将EB +油剂（O）组排除在进一步分析之外。与阴性对照组（油剂（O）+油剂（O）组和油剂（O）+ DHT组）相比，接受EB + DHT治疗的大鼠表现出显著更多的求偶行为，而EB + DHT组大鼠与阳性对照组（EB + P组）之间未观察到差异；值得注意的是，与油剂（O）+油剂（O）组相比，油剂（O）+ DHT组观察到更多的求偶行为。此外，与阴性对照组（油剂（O）+油剂（O）组和油剂（O）+ DHT组）相比，接受EB + DHT治疗的大鼠表现出显著更高的接受度指标（LR和LQ），并接受了更多的爬跨、插入和射精，达到了与EB + P组相当的水平。4组之间在雌雄爬跨或拒绝反应方面未检测到差异。从定性角度来看，完全的 solicitation 仅在EB + DHT组的T模式中发现，该组也是唯一显示包含仅求偶行为事件的高阶T模式的组。总之，在经EB预处理的OVX Long-Evans大鼠中给予DHT可增强性行为指标。具体而言，DHT似乎刺激了与交配/生殖指标分开的求偶行为序列。我们的数据支持雄激素在促进雌性性欲方面的独立作用。
