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Ovariectomy in the rat increases brain norepinephrine synthesis and turnover. The present study investigated the effect of ovariectomy and subsequent replacement of ovarian steroids on tyrosine hydroxylase activity (TH), which is purported to be the rate-limiting step in catecholamine (CA) synthesis. Animals were ovariectomized and tyrosine and tyrosine hydroxylase activity assayed 2, 4, 26 and 60 days postoperatively. Estrogen (1.5 M*g/rat) or vehicle was injected for one week beginning on day 21. Progesterone (0.5 mg or 2 mg) or vehicle was administered at 1000 hours on day 26 and the animals sacrificed 3 or 6 hours later. Ovariectomy caused a 2-3 fold increase in T H having an onset of 4 days and a duration of at least 60 days. Daily injection of estrogen for 1 week caused a 30% increase in TH. TH was significantly reduced 6 hours after injection of 0.S mg progesterone in estrogen-treated ovariectomized controls. After injection of 2 mg progesterone, TH of ovariectomized and ovariectomized estrogen-treated rats was unchanged after 3 hours, but significantly decreased at 6 hours. Thus, CA synthesis in the rat hypothalamus may be altered by ovarian steroids, with progesterone having an inhibitory effect and estrogen a stimulatory effect. The inhibitory effect of progesterone on T H was facilitated by the presence of small amounts of estrogen. (Endocrinology 9 1 : 276, 1972) M ONOAMINERGIC participation in the control of ovulation and gonadal function has been documented (1). Recent investigations suggest that hypothalamic norepinephrine (NE) synthesis and turnover are accelerated after ovariectomy (2,3), but not hypophysectomy (4), suggesting that gonadal steroids may influence catecholamine (CA) synthesis in the brain. Simultaneous replacement of estrogen and progesterone to ovariectomized rats decreases the formation of 3 H-norepinephrine from 3 H-tyrosine (2, 3).These observations prompted an investigation of the effects of ovariectomy and ovarian steroid replacement on rat hypothalamic tyrosine hydroxylase activity (TH) as a possible mechanism for gonadal steroid influence on NE synthesis. If ovariectomy increases NE synthesis, then the activity of

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