Hyperprolactinemia after neonatal prolactin (PRL) deficiency in rats: evidence for altered anterior pituitary regulation of PRL secretion.
Previous findings from this laboratory suggest a role for milk-borne PRL in the development of the inhibitory neuroendocrine controls over PRL secretion. Thus, rats that consumed milk deficient in PRL on days 2-5 postpartum show reduced concentrations and turnover of DA in the median eminence and elevated serum levels of PRL at 30-35 days of age. The present experiments were undertaken to investigate whether these consequences of neonatal PRL deficiency persist beyond puberty, and whether alterations in pituitary responsiveness to hypothalamic hormones may be involved. Lactating rats received sc injections of either saline or the dopamine (DA) agonist bromocriptine (125 micrograms/rat.day) on each of days 2-5 postpartum, a treatment that reduces the amount of PRL in milk without abolishing lactation. Blood samples were obtained from male and female offspring at various postnatal ages, and PRL concentrations were determined by RIA. Serum PRL concentrations in offspring from both groups were low until after weaning, but the female offspring of bromocriptine-treated mothers showed significantly elevated serum PRL between days 30 and 90 postpartum. Male offspring of bromocriptine-treated mothers also had transiently increased serum PRL levels, which returned to control levels by day 40. The turnover rate of DA in the median eminence, calculated from the rate of decline after synthesis inhibition, was reduced on day 35 in neonatally PRL-deficient offspring, as shown previously. However, no differences in DA turnover between the two groups were apparent on day 60, indicating a recovery of normal dopaminergic activity. Anterior pituitary cells of 100-day-old control and neonatally PRL-deficient animals were dispersed, cultured for 3 days, and then exposed to either TRH, to stimulate PRL release, or to the DA agonist bromocriptine, which inhibits PRL release. Pituitary cells of neonatally PRL-deficient offspring were almost completely unresponsive to bromocriptine with regard to suppression of PRL release and cytoplasmic PRL mRNA levels. In contrast, pituitary cells of neonatal PRL-deficient offspring were somewhat more responsive to TRH in stimulating PRL release and increasing the levels of PRL mRNA. These results suggest that a brief period of PRL deficiency during the neonatal period may result in long-lasting alterations in control of PRL secretion. The resultant hyperprolactinemia may be initiated by a reduction in the release of DA from the hyothalamus, perhaps reflecting a role for milk-derived PRL in the functional development of this neurosecretory system, and maintained in part by a reduction in pituitary responsiveness to DA.
D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D001971:Bromocriptine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D004971:Estrus; D005260:Female; D006966:Hyperprolactinemia / Q000503:physiopathology*; D007774:Lactation; D008473:Median Eminence / Q000187:drug effects / Q000378:metabolism; D010902:Pituitary Gland / Q000378:metabolism / Q000503:physiopathology*; D011247:Pregnancy; D011388:Prolactin / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012016:Reference Values; D012741:Sexual Maturation; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
D001971:Bromocriptine; D013973:Thyrotropin-Releasing Hormone; D011388:Prolactin; D004298:Dopamine