Dopamine (DA) levels, catecholamine histofluorescence and DA biosynthesis are markedly and selectively deficient in the median eminence (ME) of Snell and Ames dwarf mice. Catecholamine, possibly DA, biosynthesis in the mediobasal hypothalamus (MBH) is also deficient in the Ames dwarf mouse. Dwarfism in these animals is secondary to an absence of growth hormone (GH) and hypothyroidism. Further, these dwarf mice appear to have no circulating prolactin (PRL). Recent data suggests that PRL replacement for 2 weeks enhances DA synthesis in the Ames dwarf ME although not to the normal level. Interestingly, GH or thyroxine (T4) replacement was as effective as PRL in increasing catecholamine biosynthesis in the dwarf MBH. Collectively, these observations have led to our hypothesis that PRL has a critical and previously unsuspected role in the postnatal maturation of the tuberoinfundibular dopamine (TIDA) neuronal pathway. The nerve terminals of this pathway are responsible for the normally high levels of DA found in the ME. A combination of neurochemical, recombinant DNA and morphologic techniques will be utilized to determine (1) if there is a deficiency of TIDA cell bodies (2) if the PRL induced restoration of DA synthesis in the ME requires the synthesis of new mRNA for tyrosine hydroxylase (TH), the rate limiting enzyme in DA synthesis, (3) if GH or T4 have potent although comparatively delayed effects to enhance DA synthesis in the dwarf ME, (4) whether the postnatal development of the TIDA neurons in normal mice can be disrupted by experimentally induced hypoprolactinemia or hypothyroidism. The TIDA neuronal pathway is well recognized as the primary mechanism involved in regulating PRL secretion by the anterior pituitary. The results obtained should provide a new insight into a unique and previously unsuspected role PRL, in turn, may have on the postnatal development of the TIDA neuron pathway. In more general terms, the results should provide new information as to how the anterior hormones in general may act in the organization and development of the hypothalamic mechanisms which regulate their secretion in the adult and how the maturation of these mechanisms may be disrupted by postnatal deficiencies in circulating hormones.
| Morgan, W W; Besch, K C (1990) Effect of prolactin replacement on the number of tyrosine hydroxylase expressing neurons in the arcuate nuclei of Ames dwarf and normal mice. Neuroendocrinology 52:70-4 |
