title: The relationship between adenosine diphosphate-ribosylation and mammary gland differentiation.
abstract: Poly(adenosine diphosphate [ADP]-ribosyl)ation, although associated with differentiation in many systems, exhibited a reciprocal relationship with mammary gland differentiation, and both the synthetic and degradatory pathways complemented each other in this regard. Poly(ADP-ribosyl)synthetase activity declined during pregnancy and lactation, while poly(ADP-ribose) degradatory activity rose late in pregnancy and peaked during lactation. In explant cultures, similar changes occurred and appeared to be under separate hormonal control; prolactin suppressed the synthetase activity, whereas insulin stimulated the poly(ADP-ribosyl)glycohydrolase activity. This latter effect may be mediated by a decline in cAMP levels for the following reasons: the glycohydrolase is known to be inhibited by cAMp, insulin decreased cAMP concentrations in mammary explants by 70%, and cholera toxin blocked the effects of insulin on poly(ADP-ribose) degradation. This reciprocal relationship between poly(ADP-ribosyl)ation and mammary gland differentiation is further supported by pharmacological studies: in the presence of insulin, cortisol, and prolactin, an inhibitor of the synthetase stimulated alpha-lactalbumin three-fold over hormone stimulation alone. However, this inhibitor was unable to induce differentiation in the absence of prolactin. Therefore, although there is a close association between a decline in enzyme activity and mammary differentiation, the data are insufficient to support a causal relationship.
mesh_terms: D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002364:Caseins / Q000096:biosynthesis; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D007328:Insulin / Q000494:pharmacology; D007774:Lactation; D007788:Lactose Synthase / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D009698:Nucleoproteins / Q000378:metabolism; D009702:Nucleoside Diphosphate Sugars / Q000378:metabolism*; D009924:Organ Culture Techniques; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011247:Pregnancy; D011388:Prolactin / Q000494:pharmacology
chemical_list: D001549:Benzamides; D002364:Caseins; D007328:Insulin; D009698:Nucleoproteins; D009702:Nucleoside Diphosphate Sugars; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011064:Poly Adenosine Diphosphate Ribose; D011388:Prolactin; D000242:Cyclic AMP; D007788:Lactose Synthase; D011065:Poly(ADP-ribose) Polymerases; C025159:3-methoxybenzamide