BRAIN PROLACTIN AS A CENTRAL NEUROMODULATOR

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As a logical extension of other work from this laboratory on anterior pituitary hormone-like proteins found in rat central nervous system, the presence of an immunoreactive and bioactive prolactin widely distributed in the rat brain has been reported. This brain-based prolactin-like immunoreactivity (PLI), which is immunologically, chromatographically, and biologically similar to anterior pituitary prolactin, is not dependent on the anterior pituitary for its presence, and in hypothalamus, is largely associated with synaptosomes. In this project period we propose to extend this work to test two hypotheses, namely: 1. Brain prolactin is a locally synthesized, central neuromodulator/neurotransmitter. 2. Hypothalamic prolactin, acting together with testosterone, stimulates hypothalamic beta-endorphin secretion. This effect is partly mediated through stimulation of dopamine release. Data to support the first hypothesis will be derived from experiments designed: 1) to both directly and indirectly assess whether there is in situ brain synthesis of prolactin; 2) to determine whether prolactin in the extrahypothalamic brain is concentrated at nerve endings (as is hypothalamic prolactin); and 3) to establish in vitro that prolactin can be released from hypothalamic and extrahypothalamic brain parts by potassium- induced depolarization in a calcium dependent fashion. To demonstrate that brain prolactin possesses these attributes would strongly support the first hypothesis. Moreover, we will determine the ontogenetic pattern of acquisition of prolactin in the hypothalamus and in discrete areas of extrahypothalamic brain and compare this profile to that of prolactin in pituitary and serum. This experiment will involve animals from fetal life to old age. This data, which will provide important descriptive information, also impacts on the first hypothesis since neurotransmitters generally appear early in ontogenesis and, thus, appearance of brain prolactin early in fetal life would support a neurotransmitter status. In addition, demonstration of discrete neurochemical effects of endogenous hypothalamic prolactin, although listed operationally as a separate second hypothesis, would support the first hypothesis.