Regulation of a physiological apoptosis: mouse mammary involution.

Continuous milk production during lactation is dependent on a complex interplay of lactogenic hormones and the suckling stimulus exerted by the young. Involution can be initiated in the mouse mammary gland at any stage of lactation by removing the pups; involution then remains reversible for about 30 to 36 h. Involution in the mouse mammary gland is characterized by a massive loss of secretory epithelial cells from programmed cell death. The nuclear activation of protein kinase A and transcription factor activator protein 1 precede the irreversible phase of involution that is characterized by internucleosomal DNA fragmentation. Activation of activator protein 1 and fragmentation of chromosomal DNA can be prevented by lactogenic hormone treatment in explant cultures derived from mammary tissue at lactation. The elevation in activator protein 1 coincides with the epithelial expression of sulfated glycoprotein 2, a potential target gene of activator protein 1. Programmed cell death in the mammary gland is associated with the expression of the growth arrest gene, gas-1, and the integrin-associated protein gene, IAP, which codes for a putative Ca2+ channel that is dependent on integrin. Their potential roles during involution are discussed.