THE ROLE OF GONADAL STEROIDS IN REGULATING CIRCADIAN RHYTHMS

性腺类固醇在调节昼夜节律中的作用

• 批准号: 6111162
• 负责人: Ellen Leibenluft
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6111162
• 关键词: REM sleep; circadian rhythms; clinical research; electroencephalography; estrogens; hormone regulation /control mechanism; hormone therapy; human subject; human therapy evaluation; hypogonadism; leuprolide; melatonin; progesterone; psychopharmacology; reproductive system pharmacology; testosterone; thyrotropin

An extensive body of literature indicates that estrogen, progesterone, and testosterone play important regulatory roles in the circadian rhythms of hamsters and rats. However, this area has received little systematic attention in humans. In addition, while sleep disturbance is one of the most common complaints of peri- and post-menopausal women, little is known about the effects of the hypogonadal state, or of hormone replacement, on sleep. This experiment is designed to study the circadian rhythms and sleep of male and female volunteers under pharmacologically controlled hormonal conditions. Normal volunteers are treated with Leuprolide acetate (Lupron), a gonadotropin releasing hormone (GnRH) agonist that suppresses the endogenous secretion of gonadotropins and gonadal steroids. Hormone replacement is then prescribed, so that female subjects can be studied in three hormonal conditions (hypogonadal, estrogen, progesterone), while men are studied in two (hypogonadal, testosterone). In each hormonal condition, we study subjects' circadian rhythms and sleep using sleep logs, wrist activity monitors, rectal temperature monitors, sleep EEG, and a constant routine procedure during which plasma levels of melatonin, TSH, and prolactin are measured. Ten men have completed the study, and results indicate significant decreases in prolactin levels and in the time and percent of stage 4 sleep in the hypogonadal state, compared with testosterone replacement. In addition, there are trends toward a prolonged nocturnal temperature trough, decreased REM latency, and an increase in the time and percentage of stage 3 sleep in the hypogonadal state. In men, there are no differences in the profiles of melatonin or TSH secretion between the two hormonal conditions. Six women have completed the study, and more are being recruited. Preliminary results show a significant increase in the amplitude of nocturnal melatonin secretion in the hypogonadal state.

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