Expression of apoptosis-related proteins in mammary gland of goat

Abstract

The expression of apoptosis-related proteins: TGF-β1 (auto/paracrine inducer) and its receptor (TGF-βRIII), Bax (promoter), Bcl-2 (inhibitor) and CPP-32 (executor of apoptosis) as well as the apoptotic cell number in mammary glands of 11 Polish White Improved goats in the course of the lactation cycle (peak of lactation: days 40–70, late lactation: days 208–256, drying off: days 267–340) was investigated. The immunohistochemical study demonstrated a significant increase in TGF-β1 and TGF-βRIII expression in the lobuloalveolar tissue from the early lactation to the dry period. Our recent study on HC11 mouse mammary epithelial cells [Cell. Mol. Biol. 46 (2000) 175] has revealed an inhibitory effect of prolactin on TGF-β1 transcription, which may explain the low TGF-β1 synthesis during lactogenesis and galactopoiesis and the increase in TGF-β1 and TGF-βIIIR expression in late lactation and dry period. Bax expression was the lowest in the peak of lactation, significantly increased in late lactation and remained elevated during drying off. Bcl-2 content was lower than Bax in all examined periods, but it increased significantly at the end of lactation, which suggests the survival of cells with the highest resistance to apoptogenic stimuli. The increase in Bcl-2 level in remnant lobuloalveolar tissue is probably the molecular mechanism that limits the rate of secretory tissue involution. The induction of CPP-32 (caspase 3) from the peak of lactation to dry period was accompanied by a progressive loss of mammary epithelial cells and the increase in apoptotic cell numbers but only in the dry period. The increase in the expression of examined proteins in the late lactation and the dry period indicates their involvement in the induction (TGF-β1 and TGF-βRIII), regulation (Bax and Bcl-2) and execution (CPP-32) of programmed cell death in the course of mammary gland involution. The lack of an increase in apoptotic cell number in late lactation, in spite of the evident decrease in total cell number, suggests milk as an alternative route (apart from phagocytosis) of apoptotic cells elimination from the mammary gland. The presented results provide new insights into the molecular mechanism of mammary cell apoptosis in goat and for this reason may have practical implications for control and regulation of mammary gland remodelling, which is a prerequisite for subsequent successful lactation.