<p>The effect of sex hormones on pineal melatonin production has been examined. The diurnal profile in urinary aMT6s excretion, which is believed to represent pineal melatonin production and 24 hour sex hormone excretion was determined by RIA in male and female rats at age of 3 weeks, 2 months, 8 months, 14 months and 20 months. A concomitant decrease in metabolite excretion corrected for body weight was found with increasing age together with a highly significant sex difference in aMT6s output at 3 weeks, 2 months and 8 months of age. Increase of body weight with age is an important factor responsible for the age-related alteration while the difference in sex hormone milieu between male and female animals could be one explanation for the sex difference in aMT6s excretion in younger rats. The effect of castration on the diurnal profile in urinary aMT6s excretion was observed in both male and female rats at 3 weeks, 2 months and 8 months of age. Castration caused a fall in urinary aMT6s excretion in 3 week old female rats but increased the metabolite output in both 2 month and 8 month old female rats. In male rats castration reduced aMT6s excretion at 2 months of age but there was no significant effect at 3 weeks or 8 months of age. In addition, urinary aMT6s excretion varied with the stages of the rat oestrous cycle; the lowest excretion was observed at proestrus corresponding with the highest 24 hour urinary oestradiol excretion. Sex hormone treatment was performed on 2 month old castrated male and female rats. Both testosterone treatment on male castrated rats and oestradiol on female castrated rats abolished the effects of castration on aMT6s excretion. Administration of oestradiol to male rats and testosterone to female rats decreased and increased urinary aMT6s excretion, respectively. Castration had no significant effect on the half life of melatonin elimination from plasma either in 2 month old male and female rats or 6 month old male rats. The effect of castration and sex hormone treatment on the pineal response to isoproterenol (ISO) was also investigated in 2 month and male and female rats. Castration increased aMT6s excretion in female rats but reduced aMT6s output in male animals in both time-course and dose-dependence studies. Changes in serum and pineal melatonin response to ISO with castration and sex hormone treatment were examined by an Elisa. Consistently, castration in female rats increased pineal and serum melatonin responses to ISO and oestradiol treatment to castrated female rats blocked the elevation, whereas in male rats castration decreased the responses and testosterone treatment to castrated male rats abolished the reduction. The effect of sex hormones on pineal beta-adrenergic receptors were studied in 2 month old rats. The beta-adrenergic receptor binding was determined by using $\sp3$H-dihydroalprenolol (DHA) in single pineal glands. Castration in female rats increased the receptor density compared with oestradiol treated and sham-operated animals. By contrast, the receptor concentration in castrated male rats was lower than testosterone treated and sham-operated male animals. The results of the present study demonstrate that sex hormones are involved in the regulation of pineal melatonin production; in 2 month old rats, oestradiol has an inhibitory while testosterone exerts a stimulating effect. The effects do not result from the alteration of circulating melatonin metabolism. One of the mechanisms is that sex hormones alter the pineal response to adrenergic stimulation and act on the pineal beta-adrenergic receptors.</p> / Doctor of Philosophy (PhD)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/8587 |
| Date | 08 1900 |
| Creators | Yie, Shang-Mian |
| Contributors | Brown, G.M., Medical Sciences |
| Source Sets | McMaster University |
| Detected Language | English |
| Type | thesis |
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