Piekarski David J, Routman David M, Schoomer Elanor E, Driscoll Joseph R, Park Jin Ho, Butler Matthew P, Zucker Irving
Department of Psychology, University of California, Berkeley, Berkeley, CA 94720, USA.
Horm Behav. 2009 Jan;55(1):182-9. doi: 10.1016/j.yhbeh.2008.10.003. Epub 2008 Oct 18.
Testosterone (T) secreted in short pulses several times each day is essential for the maintenance of male sex behavior (MSB) in mammals. Blood T concentrations are relatively low during inter-pulse intervals. Assessment of androgenic influences on MSB of rodents has, with very few exceptions, involved either injections of pure or esterified hormones dissolved in oil or implantation of constant release capsules that generate supraphysiological and/or constantly elevated T concentrations. The minimum daily concentration of T necessary to maintain and restore MSB when T is delivered as a discrete short pulse remains unspecified; nor is it known whether infrequent T pulses in the physiological range sustain MSB. To address these questions, we varied T injection concentrations and frequencies in castrated, sexually-experienced Syrian hamsters. All males injected daily with an aqueous vehicle failed to display the ejaculatory reflex 5 weeks after castration. Once daily 15 microg subcutaneous T injections both maintained and restored MSB, whereas once daily 5 microg T injections resulted in fewer males ejaculating and longer ejaculation latencies. Substantially higher T doses were required to restore MSB in previous studies when T was administered in an oil vehicle. 50 microg T maintained MSB in most hamsters injected once every 4 or 7 days, despite long intervals between injections during which circulating T was undetectable or well below physiological concentrations. Some T regimens that maintained MSB were associated with subnormal seminal vesicle and ventral prostate weights. The demonstration that relatively brief, infrequent elevations of T are sufficient to support MSB provides a useful model to assess the neuroendocrine basis of MSB and raises the possibility that infrequent low dose androgen replacement protocols may restore sex behavior to hypogonadal men without inducing some of the negative side-effects associated with more frequent, higher dose treatments.
睾酮(T)每天以短脉冲形式分泌数次,这对维持哺乳动物的雄性性行为(MSB)至关重要。脉冲间期血液中的T浓度相对较低。除了极少数例外,对啮齿动物MSB雄激素影响的评估,要么涉及注射溶解在油中的纯激素或酯化激素,要么涉及植入能产生超生理和/或持续升高T浓度的缓释胶囊。当T以离散短脉冲形式给药时,维持和恢复MSB所需的每日最低T浓度仍未明确;生理范围内不频繁的T脉冲是否能维持MSB也不清楚。为了解决这些问题,我们改变了阉割且有性经验的叙利亚仓鼠的T注射浓度和频率。所有每天注射水性赋形剂的雄性在阉割5周后均未表现出射精反射。每天一次皮下注射15微克T既能维持又能恢复MSB,而每天一次注射5微克T则导致射精的雄性减少且射精潜伏期延长。在先前的研究中,当T以油剂形式给药时,需要更高的T剂量才能恢复MSB。尽管注射间隔期间循环T检测不到或远低于生理浓度,但每4天或7天注射一次50微克T能使大多数仓鼠维持MSB。一些维持MSB的T给药方案与精囊和腹侧前列腺重量低于正常有关。相对短暂、不频繁的T升高足以支持MSB这一证明,为评估MSB的神经内分泌基础提供了一个有用的模型,并增加了一种可能性,即不频繁的低剂量雄激素替代方案可能使性腺功能减退男性恢复性行为,而不会引发与更频繁、高剂量治疗相关的一些负面副作用。