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N J Hebert

Publications and source records attributed to N J Hebert.

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Restoration of lactation in bromocriptine-treated rats by prolactin replacement: comparison of constant versus pulsatile infusion and intrahepatic versus intrajugular routes of delivery.

The effectiveness of pulsed vs constant infusion of ovine(o) prolactin (PRL), given by different schedules, at restoring lactation in PRL-suppressed rats was compared, and the possibility that the liver participates in the restorative effects of the infused hormone was investigated. Lactating dams were given subcutaneous injections of bromocriptine (BC) between days 7 and 12 postpartum to suppress endogenous PRL secretion. Osmotic minipumps were used to infuse the oPRL into either the jugular vein or the hepatic portal vein. The latter route would expose the liver to higher concentrations of PRL than would intrajugular infusion. Constant infusion of oPRL in different doses was, overall, more effective at restoring lactation (i.e. litter weight gain) than was giving pulses, regardless of the site of delivery. Infusion of the PRL at 100 micrograms/rat/day in pulses of 1h duration was ineffective at frequencies of either 4 or 8/day, whereas pulses of 2h duration were effective at both of these frequencies. Infusing that dose of oPRL was equally effective whether it was given in 4 or 8 pulses/day of 2 h duration. Intrahepatic infusion of oPRL was not more effective than intrajugular delivery regardless of the schedule of administration. These results indicate that pulse duration is a more important determinant of the effectiveness of the galactopoietic action of PRL in the lactating rat than is pulse frequency. No evidence was obtained that the liver participates in the galactopoietic effects of PRL.

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On the possible role of the liver in the galactopoietic action of prolactin in the rat.

The possibility that the liver contributes to the galactopoietic effects of PRL was assessed in lactating rats in which endogenous PRL secretion was suppressed by injections of bromocriptine. Pup weight gain over a 5-day period (i.e. days 7-12 of lactation) was used as an index of lactational performance in dams. Osmotic minipumps were used to infuse different doses of ovine (o) PRL into either the external jugular vein (JV) or the hepatic portal vein of the dams at a constant rate. The latter route of delivery would directly expose the liver to a higher concentration of PRL than would the former one. Twice daily sc injections of bromocriptine (1.5 mg/kg.injection) in corn oil into the dams completely suppressed litter weight gain. Infusion of oPRL into the JV at a dose of 2.0 mg/rat.day restored lactation to normal in the drug-treated mothers. Electrophoretic analysis indicated that about 95% of the oPRL remained in the intact monomeric form when incubated in the infusion solvent in the minipump at 37 C for 2 days, but by 4 and 6 days of incubation the amounts of that form decreased by about 25% and 50%, respectively. Measurement of serum oPRL levels by RIA showed that they were fairly constant, and after 5 days of infusion, the final concentration was directly related to the dose infused. Continuous infusion of oPRL into the JV was equally effective at restoring pup weight gain as was infusion into the hepatic portal vein over a wide range of doses. Hence, a physiological role of the liver in the maintenance of lactation by PRL is not supported by these experiments.

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Lactogenic hormones stimulate the liver to secrete a factor that acts synergistically with prolactin to promote growth of the pigeon crop-sac mucosal epithelium in vivo.

We have investigated whether the liver is a source of a PRL-synergizing activity (i.e. synlactin) and we have obtained some information on endocrine control of its secretion. Livers were removed from 3-month-old Long-Evans rats (male, virgin, pregnant, or lactating female) or from virgin females that were injected with saline, bovine GH, or ovine PRL for 7 days, and hepatic slices were prepared for in vitro incubation in medium 199. The media were tested for synlactin activity by determining whether they could augment the pigeon crop-sac response to locally injected ovine PRL. Only the media containing factors from the liver of pregnant or lactating females and PRL-injected virgins had significant synlactin activity. They augmented the crop-sac mucosal growth response by 130%, 140%, and 103%, respectively. Medium in which slices of kidney from virgin or pregnant rats were incubated did not have detectable synlactin activity. The medium samples that had synlactin activity were also tested for the presence of bioactive (crop-sac assay) and immunoreactive (RIA) rat PRL, and none had detectable amounts of the hormone. Hence, the augmenting effect is not due to PRL that is sequestered in and released by the liver. The levels of insulin-like growth factor I/somatomedin-C in medium samples that did or did not have synlactin activity (from pregnant and virgin females, respectively) were measured by RIA and were found to be equivalent. Hence, synlactin activity is probably not due to insulin-like growth factor I. Overall, our results indicate that lactogenic hormones (i.e. pituitary PRL, and presumably placental lactogens in the pregnant rats) stimulate the liver to secrete synlactin activity. The hepatic PRL receptors which increase in number in pregnant females may be involved in the secretion of synlactin, which could then act in concert with ovarian steroids and GH and/or PRL to promote mammary growth.

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