When lactating rats are injected with the dopamine (DA) agonist bromocriptine during days 2-5 postpartum, which substantially decreases the concentrations of PRL in mild without abolishing lactation, their offspring exhibit decreased activity of the tuberoinfundibular DA (TIDA) system and elevated serum PRL as young adults. In addition, in the adult, there are more cells in the pituitary glands for neonatal PRL-deficient rats, and their lactotrophe cells show decreased responsiveness to the PRL- inhibiting effects of DA and increased responsiveness to the PRL- stimulating effects of TRH. These effects 1) are not due to non- specific effects of bromocriptine since essentially undetectable levels of the drug pass from the mother to the neonate via the milk; 2) are prevented by the replacement of PRL to bromocriptine treated mothers; and 3) do not occur if bromocriptine is administered to the mothers during the second postnatal week. These findings suggest the hypothesis that milk-derived PRL in the neonate influences the growth and/or maturation of TIDA neurons as well as pituitary lactotrophes, and that a deficiency in mile- derived PRL during a critical postnatal period may have long- lasting consequences for neuroendocrine regulation of PRL secretion.
The specific aims of the present proposal are: 1) to establish the normal time course for the functional development of the TIDA system, using measurements of DA concentration and synthesis rate, and to test the effects of PRL ad of neonatal PRL deficiency on the course of this development; 2) to investigate the effects of neonatal PRL deficiency on the numbers of TIDA neurons, using immunocytochemistry for tyrosine hydroxylase; 3) to examine whether neonatal PRL deficiency alters the response of TIDA neurons to their normal regulatory influences, using in vivo and in vitro approaches; 4) to investigate the consequences of neonatal PRL deficiency on the adult regulation of PRL synthesis and release by stimulatory or inhibitory hypophyseotropic hormones, or by estradiol, using cultured anterior pituitary cells; 5) to test whether the receptor binding of hypophyseotropic hormones and/or their coupling to a second messenger system, such as adenylate cyclase/cAMP, are permanently altered by neonatal PRL deficiency; 6) to test whether neonatal PRL deficiency affects the numbers and/or morphology of pituitary lactotrophe cells, the secretory forms of PRL, and the characteristics of PRL secretion from lactotrophe cells over the lifespan of the rat.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Method to Extend Research in Time (MERIT) Award (R37)
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Reproductive Biology Study Section (REB)
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Pennsylvania State University
Schools of Arts and Sciences
University Park
United States
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