Long-Term, Homologous Prolactin, Administered through Ectopic Pituitary Grafts, Induces Hypothalamic Dopamine Neuron Differentiation in Adult Snell Dwarf Mice

Abstract

Pituitary prolactin (PRL) secretion is inhibited by dopamine (DA) released into the portal circulation from hypothalamic tuberoinfundibular DA (TIDA) neurons. Ames (df/df) and Snell (dw/dw) dwarf mice lack PRL, GH, and TSH, abrogating feedback and resulting in a reduced hypophysiotropic TIDA population. In Ames df/df, ovine PRL administration for 30 d during early postnatal development increases the TIDA neuron number to normal, but 30 d PRL treatment of adult df/df does not. The present study investigated the effects of homologous PRL, administered via renal capsule pituitary graft surgery for 4 or 6 months, on hypothalamic DA neurons in adult Snell dw/dw mice using catecholamine histofluorescence, tyrosine hydroxylase immunocytochemistry, and bromodeoxyuridine immunocytochemistry. PRL treatment did not affect TIDA neuron number in normal mice, but 4- and 6-month PRL-treated dw/dw had significantly increased (P ≤ 0.01) TIDA (area A12) neurons compared with untreated dw/dw. Snell dwarfs treated with PRL for 6 months had more (P ≤ 0.01) TIDA neurons than 4-month PRL-treated dw/dw, but lower (P ≤ 0.01) numbers than normal mice. Periventricular nucleus (area A14) neuron number was lower in dwarfs than in normal mice, regardless of treatment. Zona incerta (area A13) neuron number was unchanged among phenotypes and treatments. Prolactin was unable to induce differentiation of a normal-sized A14 neuron population in dw/dw. Bromodeoxyuridine incorporation was lower (P ≤ 0.01) in 6-month PRL-treated normal mice than in 6-month PRL-treated dwarfs in the subventricular zone of the lateral ventricle and in the dentate gyrus, and lower (P ≤ 0.05) in 4-month untreated dwarfs than in 4-month untreated normal mice in the median eminence and the periventricular area surrounding the third ventricle. Thus, a PRL-sensitive TIDA neuron population exists in adult Snell dwarf mice when replacement uses homologous hormone and/or a longer duration. This finding indicates that there is potential for neuronal differentiation beyond early developmental periods and suggests plasticity within the mature hypothalamus.