LACTOGENIC ACTIONS OF DIFFERENT GROWTH-HORMONE PREPARATIONS IN PREGNANT AND LACTATING RATS

We studied the capacity of different GH preparations, natural human (h )GH, recombinant hGH (rhGH), rat (r)GH, ovine (o)GH, bovine (b)GH and porcine (p)GH, and ovine prolactin (oPRL), to stimulate lactogenesis i n ovario-hysterectomized pregnant rats or intact lactating rats treate d with bromocriptine (BC). Ovariohysterectomy (OVX-HYS) performed at 0 800 h on day 19 of pregnancy induced lactogenesis, i.e. increases in m ammary casein and lactose and positive response to the oxytocin test, 28 h later. Lactogenesis was prevented by treatment with BC (1.5 mg/kg ) immediately after surgery (OVX-HYS-BC). The hormones were given at d oses of 0.25 or 0.5 mg/rat (except rhGH given only at 0.5 mg/rat) at 1 200 and 2000 h on day 19. Casein was increased by both doses of oPRL a nd hGH, rhGH and 0.25 mg oGH, and lactose by both doses of oPRL, rhGH and 0.25 mg rGH. The other GH preparations had no effect. The oxytocin test demonstrated the presence of milk in the mammary tissues of the OVX-HYS rats and in the OVX-HYS-BC plus oPRL (0.25 and 0.5 mg) or rhGH -treated groups. Injection of BC to pregnant rats at 2000 h on day 20 and at 0800 h on day 21 decreased litter growth on the first 4 days po stpartum. Two-thirds of the litters resumed growth after day 4, indica ting the recuperation of milk production, while the rest never recuper ated. Serum prolactin in BC-treated rats was reduced until day 4 postp artum. On day 6 the rats which had recuperated had normal values, whil e those which had still not recuperated had lower values. BC-treated r ats were injected s.c. with 0.25 mg each of oPRL, hGH, rGH, oGH, bGH o r pGH, or 0.25 or 0.5 mg rhGH/rat, immediately postpartum and 12, 24 a nd 36 h later. hGH and 0.5 mg rhGH induced levels of milk production s imilar to controls except on day 3. oPRL and rhGH (0.25 mg), induced a partial reversion of the effect of BC. rGH and oGH had a slight effec t on days 1 and 2 and all the litters resumed growth on day 7. In cont rast, pGH and bGH were inactive. The affinity of hGH for the prolactin receptor, measured as displacement of I-125-labelled oPRL binding to crude Liver membranes, was comparable with that of oPRL. While rhGH wa s ten times less active than oPRL, rPRL was 100 times lower and all th e other GH preparations had at least 10(4) times lower capacity to dis place I-125-labelled oPRL. These results indicate that both natural an d recombinant hGHs are potent inductors of milk synthesis in pregnant or lactating rats, most probably due to their actions at the level of the prolactin receptor. rGH and oGH have a partial action, while pGH a nd bGH seem to be inactive. The actions of non-human GHs may be explai ned by their somatogenic properties exclusively, and indicate that GH may play a role in the optimization of milk production during lactatio n and an accessory role in the induction of lactogenesis in pregnant r ats.