Lincoln G A
MRC Reproductive Biology Unit, Centre for Reproductive Biology, Edinburgh, Scotland.
J Pineal Res. 1992 Apr;12(3):135-44. doi: 10.1111/j.1600-079x.1992.tb00040.x.
The biological effects of administering melatonin into the mediobasal hypothalamus (MBH) was documented in adult Soay rams using two delivery systems: (1) microimplants in the MBH delivering melatonin continuously and (2) microdialysis probes in the MBH delivering melatonin intermittently as a daily timed infusion. The experimental protocol was to precondition rams to long days (LD 16:8) for 10 to 12 weeks, and then introduce the exogenous source of melatonin by implantation or infusion. Sixteen rams were divided equally into four treatment groups: (a) microimplants in the MBH, (b) microdialysis probes in the MBH, (c) empty microimplants in the MBH to act as sham-operated controls, and (d) no surgery to act as unoperated controls. The microimplants consisted of 22-gauge stainless steel cannulae with melatonin fused inside the tip and were placed bilaterally in the brain for 14 weeks. These implants had previously been shown to release melatonin at a relatively constant rate when incubated in buffered saline at 37 degrees C (3.42 +/- 0.42 micrograms/24 hr, mean +/- SEM, 1-10 weeks) and to produce a localised concentration of melatonin when implanted in the brain (localised to within 1 mm of the center of the implant). The microdialysis probes were also 22-gauge cannulae with a 3 mm membrane (Biotech). They were placed bilaterally into the MBH, connected to two portable syringe drivers secured to a backpack. Melatonin was infused daily for 10 hr (estimated delivery: 0.5 microgram/hr) starting in the mid-light phase to produce a long-duration intermittent melatonin signal. Technical problems limited the period of infusions to 8-10 weeks with minor interruptions. Animals from all groups were maintained on long days, and the observations extended for a period of 28 weeks. The melatonin implants placed in the MBH induced a premature increase in the blood concentrations of FSH and growth of the testes. This treatment also induced a marked decrease in the plasma concentrations of prolactin and the earlier development of the long winter pelage. These changes were reversed after the end of treatment with a decline in the plasma concentrations of FSH and regression of the testes, and an increase in the concentrations of prolactin and moult of the winter pelage. Daily infusions of melatonin from the microdialysis probes in the MBH produced qualitatively similar, but less marked responses. The overall results illustrate that the administration of melatonin into the MBH, either continuously or intermittently, to extend the duration of the daily melatonin signal, induces multiple short-day responses.(ABSTRACT TRUNCATED AT 400 WORDS)
利用两种给药系统记录了向成年索艾羊下丘脑中间基底部(MBH)注射褪黑素的生物学效应:(1)在MBH植入微植入物持续释放褪黑素;(2)在MBH植入微透析探针,作为每日定时输注间歇性释放褪黑素。实验方案是先让公羊适应长日照(16小时光照:8小时黑暗)10至12周,然后通过植入或输注引入外源性褪黑素。16只公羊被平均分为四个治疗组:(a)在MBH植入微植入物;(b)在MBH植入微透析探针;(c)在MBH植入空的微植入物作为假手术对照;(d)不做手术作为未手术对照。微植入物由22号不锈钢套管组成,尖端内部融合有褪黑素,双侧植入大脑14周。这些植入物先前已证明,在37摄氏度的缓冲盐水中孵育时,能以相对恒定的速率释放褪黑素(3.42±0.42微克/24小时,平均值±标准误,1 - 10周),并且植入大脑后能产生局部褪黑素浓度(局限于植入物中心1毫米范围内)。微透析探针也是22号套管,带有3毫米的膜(生物技术公司生产)。它们双侧植入MBH,连接到固定在背包上的两个便携式注射器驱动器。从光照中期开始,每天输注褪黑素10小时(估计给药量:0.5微克/小时),以产生长时间的间歇性褪黑素信号。技术问题使输注期限制在8 - 10周,有轻微中断。所有组的动物都维持长日照饲养,观察期延长至28周。植入MBH的褪黑素植入物导致促卵泡激素(FSH)血液浓度过早升高以及睾丸生长。这种治疗还导致催乳素血浆浓度显著降低以及冬季长毛过早发育。治疗结束后,这些变化发生逆转,FSH血浆浓度下降,睾丸退化,催乳素浓度升高,冬季毛发脱落。从MBH的微透析探针每日输注褪黑素产生了定性相似但不太明显的反应。总体结果表明,向MBH连续或间歇性注射褪黑素以延长每日褪黑素信号的持续时间会诱发多种短日照反应。(摘要截选至400字)