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 in ovario-hysterectomized pregnant rats or intact lactating rats treated with bromocriptine (BC). Ovariohysterectomy (OVX-HYS) performed at 0800 h on day 19 of pregnancy induced lactogenesis, i.e. increases in mammary 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 doses of 0.25 or 0.5 mg/rat (except rhGH given only at 0.5 mg/rat) at 1200 and 2000 h on day 19. Casein was increased by both doses of oPRL and 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 postpartum. Two-thirds of the litters resumed growth after day 4, indicating the recuperation of milk production, while the rest never recuperated. Serum prolactin in BC-treated rats was reduced until day 4 postpartum. On day 6 the rats which had recuperated had normal values, while those which had still not recuperated had lower values. BC-treated rats were injected s.c. with 0.25 mg each of oPRL, hGH, rGH, oGH, bGH or pGH, or 0.25 or 0.5 mg rhGH/rat, immediately postpartum and 12, 24 and 36 h later. hGH and 0.5 mg rhGH induced levels of milk production similar 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 effect on days 1 and 2 and all the litters resumed growth on day 7. In contrast, pGH and bGH were inactive. The affinity of hGH for the prolactin receptor, measured as displacement of 125I-labelled oPRL binding to crude liver membranes, was comparable with that of oPRL. While rhGH was ten times less active than oPRL, rPRL was 100 times lower and all the other GH preparations had at least 10(4) times lower capacity to displace 125I-labelled oPRL.(ABSTRACT TRUNCATED AT 400 WORDS)
Carón
R W
RW
Laboratorio de Reproducción y Lactancia, LARLAC-CONICET, Mendoza, Argentina.
Jahn
G A
GA
Deis
R P
RP
D000818:Animals; D001971:Bromocriptine / Q000494:pharmacology; D002417:Cattle; D005260:Female; D013006:Growth Hormone / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007044:Hysterectomy; D007774:Lactation / Q000187:drug effects*; D008099:Liver / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000187:drug effects*; D010052:Ovariectomy; D010121:Oxytocin; D011247:Pregnancy; D011270:Pregnancy, Animal; D011388:Prolactin / Q000097:blood / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D018000:Receptors, Peptide / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D012756:Sheep; D013552:Swine
D018000:Receptors, Peptide; D011994:Recombinant Proteins; C028202:placental lactogen receptor; D001971:Bromocriptine; D010121:Oxytocin; D011388:Prolactin; D013006:Growth Hormone