Abstract
Progesterone plays a pivotal role during mammogenesis and serves as an inhibitor of the secretory activation of mammary cells in the last days of gestation. However, its role during lactogenesis, in particular its involvement in lipid metabolism, and milk fat content and composition, is unknown. Here, we provide new evidence of progesterone's involvement in the regulation of milk fat globule (MFG) synthesis and secretion. Findings from both in vivo and in vitro studies indicated that the concentration and the direction (increase vs. decrease) of progesterone concentration to which the mammary epithelial cells (MECs) are exposed affect MFG size. This was found to be very-low-density lipoprotein (VLDL) dependent: in the presence of VLDL, the proportion of MEC with small lipid droplets (<1 μm) increased 2.4-fold, and the proportion of large lipid droplets (>1 μm) increased 4-fold; in the absence of VLDL, no differences were found. The findings add to our understanding of the mechanism underlying the regulation of MFG size and provide new evidence for progesterone's role in lipid metabolism in the mammary gland during lactogenesis. The fact that the size, synthesis, and composition of MFG are affected by the cyclic pattern of progesterone concentration in the circulation might have physiologically relevant consequences, in particular on milk as a nutritional source.
Highlights
The role of progesterone in mammogenesis [1] and secretory activation of mammary cells in the last days of gestation has been thoroughly studied and well-documented [2]
In agreement with previous studies, the findings of the current study indicate that progesterone does not have any direct effect on milk production or fat content during the estrous cycle
It is well-accepted that the reproductive hormones estradiol and progesterone do not affect milk production during the estrous cycle [23]
Summary
The role of progesterone in mammogenesis [1] and secretory activation of mammary cells in the last days of gestation has been thoroughly studied and well-documented [2]. There are some evidences that progesterone is involved in lipid metabolism pathways in the mammary gland. This process include synthesis, secretion, and size regulation of milk fat globules (MFGs), regulation of total fat content in the cell, as well as the stability of its membranes [reviewed by Argov-Argaman [3]]. Whether progesterone is involved in the regulation of MFG synthesis and secretion has never been studied. Progesterone’s possible role in regulating MFG composition and structure has not been documented
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