Changes in Hypothalamic Catecholamine Neurotransmitters and Pituitary Gonadotropins in the Immature Female Rat: Relationships to the Gonadostat Theory of Puberty Onset*

Abstract

The distribution of hypothalamic norepinephrine and dopamine tissue concentrations and the relative differences in norepinephrine turnover rate were studied in sexually maturing female rats. A modified radioenzymatic assay was used to measure norepinephrine and dopamine concentrations. Norepinephrine turnover was estimated by calculating the disappearance rate of intraventricularly injected [³H]norepinephrine over 24 h, with a correction for dilution of specific activity by endogenous norepinephrine tissue stores. Hypothalamic catecholamine content and norepinephrine turnover values were determined for the median eminence, anterior hypothalamus, and residual hypothalamus in 21-, 24-, 28-, and 31-day-old intact and 1-week postcastration animals. In addition, basal, postcastration, and post-LHRH serum LH and FSH levels were measured. In the intact rats, basal and post-LHRH LH and FSH levels did not change with age. Norepinephrine content in the anterior hypothalamus and residual hypothalamus of the intact rats increased 100% from 21–31 days of age. No age-related changes in norepinephrine in the median eminence or in dopamine in any area of the hypothalamus were seen. LH and FSH increased after castration, with the levels attained being inversely related to age. Norepinephrine concentrations in the anterior and residual hypothalami but not in the median eminence increased 30–40% post castration at 21–28 days of age. Norepinephrine turnover increased with age and was usually elevated after castration, with the greatest postcastration rise in norepinephrine turnover occurring in the youngest animals. Thus, the postcastration rises in both norepinephrine turnover and the gonadotropins (LH and FSH) were negatively correlated with age. These data suggest that norepinephrine turnover in the anterior and residual hypothalami of immature animals is inhibited by gonadol steroids and that this inhibitory effect diminishes with age. These results are consistent with the concept that a decreasing negative feedback sensitivity of the hypothalamus to gonadol steroids occurs during sexual maturation in the rat. This decrease in sensitivity may be mediated by hypothalamic norepinephrine. (Endocrinology 106: 1253, 1980)