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Title: Transplacental transfer of a growth hormone-releasing hormone peptide from mother to fetus in the rat.

Author
item Fiorotto, Marta
item LOPEZ, RUSMELY - BAYLOR COLL OF MEDICINE
item OLIVER, WILLIAM - BAYLOR COLL OF MEDICINE
item KHAN, AMIR - ADVISYS, INC.
item DRAGHIA-AKLI, RUSANDRA - ADVISYS, INC.

Submitted to: DNA and Cell Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/9/2006
Publication Date: 8/25/2006
Citation: Fiorotto, M.L., Lopez, R., Oliver, W.T., Khan, A.S., Draghia-Akli, R. 2006. Transplacental transfer of a growth hormone-releasing hormone peptide from mother to fetus in the rat. DNA and Cell Biology. 25(8):429-437.

Interpretive Summary: We have shown previously that maternal levels of growth hormone-releasing hormone (GHRH) levels, whether artificially or naturally altered, can impact the long-term growth of the subsequent generation starting at birth. We do not know if GHRH can cross the placenta from the mother to the fetus. Thus, to establish whether the effects of maternal GHRH on the offspring resulted indirectly from effects of the hormone on the mother, or by direct effects on the fetus, it was necessary to determine whether GHRH can cross the placenta. To accomplish this, pregnant rat dams were infused for 2 days with the hormone that had been radioactively labeled. We then determined if the undegraded hormone was present in the fetus. We identified the intact, labeled hormone in the stomach contents, head, and liver of the fetuses with the highest levels being present in the liver. This is the first demonstration that this hormone is capable of crossing the placenta from the mother to the fetus. It means, therefore, that factors that alter maternal levels of the hormone can have permanent, but nongenetic, effects on the growth of the offspring.

Technical Abstract: Previous studies showed that when growth hormone-releasing hormone (GHRH) was administered to either pregnant rats or pigs as a plasmid-mediated therapy, pituitary weight, somatotroph and lactotroph numbers, and postnatal growth rate of the offspring increased. To determine if these responses resulted from direct effects of GHRH on the fetus or were secondary to effects incurred in the mother, we studied in the rat the transplacental transfer of a GHRH analog (HV-GHRH) to the fetus from the maternal circulation. For the "in vivo" study, HV-GHRH was labeled with [125]I and purified by reverse-phase high-performance liquid chromatography (HPLC). At 18 days of gestation, pregnant dams were administered a priming intravenous dose followed by a constant infusion of the labeled peptide. Approximately 2 days later, intact [125]I]-HV-GHRH was isolated from the fetal liver, stomach contents, and brain. The amounts of tracer were positively correlated with those present in the corresponding dam's plasma. These data suggest that a GHRH analog of nonplacental origin, even at physiologic concentrations, can cross the placenta and, therefore, has the potential to influence fetal pituitary development directly.