Inhibition of casein synthesis by progestagens in vitro: modulation in relation to concentration of hormones that synergize with prolactin.
We studied the effect of progesterone and its agonist, R 5020, on casein and transferrin production in pregnant rabbit mammary gland explant culture and its modulation by hormones that synergize with prolactin. The glands were obtained from rabbits on days 12-14 of gestation. The progestins had no effect alone, but significantly inhibited ovine and porcine prolactin stimulation of casein synthesis in a dose dependent manner. There were no effects on transferrin content of the tissue, demonstrating a specific effect of progesterone on casein synthesis. In approx 15% of the cultures, prolactin stimulated casein production to very high levels and the progestins lost their inhibitory action. Progestins were also ineffective when the tissue was cultured with prolactin and unphysiologically high levels of insulin (5 mg/l) or cortisol (280 nmol/l), which stimulated casein synthesis to higher levels than prolactin alone. The concentration of cortisol used was 10 times higher than the serum levels seen in rabbits at the stage of gestation studied (approx 10 ng/ml) and corresponded to levels seen at the end of gestation, a period when the glands are secreting milk and progesterone serum levels have commenced to decrease. Thus, when the prolactin effect upon casein synthesis had been potentiated, whether spontaneously or through synergism with insulin or corticoids, progestins were unable to inhibit it, as is the case in lactating tissues. The results show that utilization of unphysiological levels of hormones in culture may distort the response of the tissue, masking responses that are clearly seen in vivo.
Jahn
G A
GA
Laboratoire de Physiologie de la Lactation, INRA-CNRZ, Jouy en Josas, France.
Djiane
J
J
Houdebine
L M
LM
D000818:Animals; D002364:Caseins / Q000096:biosynthesis*; D046508:Culture Techniques; D004357:Drug Synergism; D005260:Female; D006854:Hydrocortisone / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000378:metabolism*; D009649:Norpregnadienes / Q000494:pharmacology*; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology*; D011388:Prolactin / Q000494:pharmacology*; D011397:Promegestone / Q000494:pharmacology*; D011817:Rabbits; D014168:Transferrin / Q000096:biosynthesis
D002364:Caseins; D007328:Insulin; D009649:Norpregnadienes; D014168:Transferrin; D011374:Progesterone; D011388:Prolactin; D011397:Promegestone; D006854:Hydrocortisone