Molecular regulation of luteal progesterone synthesis in domestic ruminants

Regulation of progesterone secretion from the corpus luteum during the oestrous cycle requires the integration of multiple signals to achieve the appropriate amount of progesterone to maximize reproductive efficiency. Development of a mature corpus luteum capable of secreting sufficient amounts of progesterone is dependent upon the pituitary hormones LH and growth hormone (GH). Continued secretion of progesterone from the mature corpus luteum is also dependent upon pituitary hormones. If pregnancy does not occur, prostaglandin F2 alpha (PGF2 alpha) of uterine origin causes a precipitous decrease in progesterone secretion and demise of the corpus luteum. A major point of regulation of progesterone secretion by both luteotrophic and luteolytic hormones appears to be regulation of transport of cholesterol through the mitochondrial membranes to cytochrome P450scc. It is likely that both luteotrophic and luteolytic hormones regulate steroidogenic acute regulatory protein (StAR), which facilitates transport. Regulation may be occurring through increases or decreases in gene transcription, translation efficiency or post-translational modifications such as phosphorylation. Thus, although synthesis of progesterone is a complex process, both positive and negative regulation of the process appears to occur primarily at a single step (transport of cholesterol to the inner mitochondrial membrane) in the pathway.