The role of prolactin in development of the hypothalamic arcuate nucleus
Description
In genetically growth hormone (GH)- and prolactin (PRL)-deficient Ames (df/df) dwarf mice, the hypothalamic arcuate nucleus exhibits, increased numbers of GH-releasing hormone (GHRH) neurons, and reduced numbers of PRL-inhibitory tuberoinfundibular dopaminergic (TIDA) neurons, suggesting that GH and PRL are required for its normal development. The studies described here characterized further certain abnormalities of, and tested the role of PRL in, arcuate nucleus development. The TIDA neuron deficit develops after the second postnatal week, and PRL replacement initiated at 12, but not at 21, 30 or 60 days of age, was effective in preserving the TIDA population. This effect regressed after PRL withdrawal, indicating a permanent requirement for PRL. Significant serum PRL in df/df nursing pups suggested that maternally-derived PRL may influence the early postnatal development of TIDA neurons. Tract-tracing studies of median eminence (ME) innervation revealed that the reduction in df/df ME GHRH immunostaining does not appear to be the result of reduced numbers of ME-projecting GHRH cells, that the reduction in df/df ME GH-inhibitory somatostatin (SRIH) appears to be proportional to the decrease in the number of detectable ME-projecting PeN SRIH neurons, and that the deficit in df/df ME dopamine (DA) appears to be the result of a combination of reduced TIDA population and a further deficit in ME innervation by extant TIDA neurons. Numbers of ME-projecting df/df TIDA neurons increased after PRL treatment. Numbers of galanin-producing, but not neurotensin-positive or ME-projecting, neurons are reduced, in the df/df arcuate nucleus. Neonatal PRL replacement did not affect GHRH neuron number, indicating that a phenotype switch from DA-to GHRH-producing does not account for either the decrease in TIDA cells or the increase in GHRH neurons. Among the TIDA neurons, the dorsal and ventral subpopulations appear to be differentially protected by the blood-brain barrier and may be differentially affected by circulating PRL. Gene transcription activation in the arcuate nucleus was not evidenced by Fos expression after acute PRL treatment in either normal or df/df mice. These studies provide strong support for the hypothesis that PRL plays a critical role in insuring proper postnatal development of the TIDA neurons