Monoamine Biosynthesis in Hypothalamic Regions of Dwarf Mice: Effect of Replacement of Deficient Anterior Pituitary Hormones

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Abstract
Female Ames dwarf and phenotypically normal female mice were killed 30 min after treatment with NSD-1015, an aromatic L-amino acid decarboxylase inhibitor. The accumulation of dihydroxyphenylalanine (DOPA) and 5-hy-droxytryptophan were measured by high-performance liquid chromatography with electrochemical detection and provided estimates of the endogenous biosynthesis of dopamine (DA) in the median eminence (ME) and serotonin biosynthesis (5-HT) in all brain regions which were examined. Dopamine synthesis was markedly suppressed in the ME while 5-HT synthesis was enhanced in both the ME and mediobasal hypothalamus (MBH) of dwarfs as compared to phenotypically normal mice. Overall, catecholamine biosynthesis (DOPA accumulation) was suppressed in the MBH of the dwarf mice but was not different from that observed in normal mice in the preoptic area anterior hypothalamus (POA-AH). The biosynthesis of 5-HT was not different in the POA-AH of dwarf mice as compared to normal mice. In the second experiment dwarf mice received saline vehicle, ovine prolactin (PRL), growth hormone (GH) or thyroxin (T4) daily for 14 days. Normal mice received saline only. Replacement with PRL significantly enhanced DA synthesis in the ME and was the only hormone to suppress significantly the elevation of 5-HT synthesis normally observed in the ME and the MBH of the dwarfs. Both GH and T4 only partially reduced 5-HT synthesis in the ME and MBH so that this parameter was no longer statistically different from either saline-treated dwarfs or normal mice. These results suggest that the deficiency of DA in the dwarf mouse ME may be due in part to a reduced synthesis of this amine in the tuberoinfundibular dopaminergic neurons, and PRL replacement is most effective in elevating this parameter to a level approaching that observed in normal mice. The enhancement of 5-HT synthesis in the ME and MBH of the dwarfs may reflect the absence of a normal inhibitory feedback effect of circulating PRL on this parameter. Such a mechanism would be suggestive of a potential stimulatory role for hypothalamic 5-HT in regulating PRL secretion. Potential relationships between hypothalamic 5-HT and GH or T4 are less clearly demonstrable but cannot be discounted.