Norepinephrine is a major regulator of the release of growth hormone. Diethyldithiocarbamate, a dopamine-\g=b\-hydroxylase inhibitor, reduces norepinephrine synthesis and acutely inhibits growth hormone (GH) secretion. To investigate the long-term effects of dopamine-\g=b\-hydroxylase blockade on growth, we administered diethyldithiocarbamate (0, 40, 100 or 400 mg/kg sc b.i.d.) to 21-day-old female rats for 10 days. Food intake, body weight, and tail length were measured twice a week. Plasma GH levels and hypothalamic dopamine and norepinephrine content were measured; messenger ribonucleic acids (mRNAs) for GH-releasing hormone and somatostatin were determined by quantitative in situ hybridization. Diethyldithiocarbamate administration decreased GH levels (p<0.05) and retarded growth in a dose-dependent manner (p<0.05), without altering food intake. Co-administration of GH partially reversed the growth retardation in diethyldithiocarbamate-treated animals (p<0.05). Diethyldithiocarbamate treatment also increased the hypothalamic dopamine/ norepinephrine ratio (1.13 vs 0.41 control, p<0.05). Local levels of GH-releasing hormone and somatostatin mRNA were not altered by treatment. After discontinuation of diethyldithiocarbamate, growth rates returned to normal or transiently even to supranormal values. Norepinephrine synthesis blockade with diethyldithiocarbamate provides a model for reversible growth retardation, in which GH levels are decreased in the absence of decreased GH-releasing hormone mRNA. These results support a role for norepinephrine in the regulation of normal growth. Saul Malozowski, Food and Drug Administration, 5600 Fishers Lane, HFD-510 Rockville, MD 20857, USA Growth hormone deficiency (GHD) is an important endocrine cause of short stature and can occur as a permanent or transient condition (1). After reversal of GHD or GH-resistant states, such as malnutrition, subjects resume normal growth velocity but the extent of accelerated "catch-up" growth varies.Three rodent models of GHD have been developed: hypophysectomy (2), neonatal administration of monosodium glutamate (MSG) (3-6) and the inbred dwarf mouse (7, 8). Hypophysectomy produces many other hormonal deficiencies besides GHD. Administration of toxic amino acids such as MSG results in abnormal behavior, such as tail self-mutilation; and there may be other hormonal abnormalities besides GHD. Colonies of inbred strains are difficult to obtain and to breed, and hormonal or metabolic alterations other than GHD also may cause growth retardation. All of these models have irreversible GHD. * This work was presented in part at the Endocrine Society Annual Meeting, Atlanta, 1990. Norepinephrine (NE) is an important regulator of GH secretion in the brain (9, 10). Exogenous administration of NE or other a-adrenergic agonists evokes GH secretion (11,12). Blockade of NE synthesis using the dopamine-/?-hydroxylase (DBH) inhibitor diethyldithiocarbamate (DDTC) (13, 14) has been studied widely as a means of acutely suppressing GH secretion. As DDTC ad...