Mechanisms associated with acquisition of luteolytic capacity in the porcine corpus luteum.

摘要

The corpus luteum (CL) is an endocrine organ that secretes progesterone in support of pregnancy. During each reproductive cycle in mammals, a new CL develops from the follicular cells remaining after ovulation. If pregnancy does not occur, the CL regresses in a process called luteolysis. Prostaglandin F2α (PGF2α) is the hormone that causes luteolysis. Exogenous PGF2α also cause luteolysis, but only in the latter part of the cycle. During the first 3–14 days after ovulation, PGF2α is not able to induce luteolysis. The CL during this period lack luteolytic capacity. During CL development, the CL acquire luteolytic capacity and PGF2α is now able to cause luteolysis. The mechanisms allowing acquisition of luteolytic capacity are undefined. Lack of luteolytic capacity is not due to the absence of receptors for PGF2α (FP receptors) on luteal cells. In the studies presented herein, acquisition of luteolytic capacity in the porcine CL is associated with changes in the responses to PGF2α. Treatment of porcine CL with PGF2α before and after acquisition of luteolytic capacity generated two types of physiological responses. One group of responses occurred in both CL with and without luteolytic capacity. These responses include induction of c-fos, JunB, FosB, Cox-2 mRNA and inhibition of FP receptor and 3βHSD mRNA. A second group of responses occurred only in CL with luteolytic capacity. These responses include induction of luteal estradiol and PGF2α secretion, a decrease in progesterone production and an induction of estrogen receptor-β and c-jun mRNA. Induction of estradiol is regulated by an increase in aromatase mRNA, while inhibition of progesterone occurs by a decrease in a protein called steriodogenic acute regulatory protein. The regulation of luteal PGF2α is unexplained since the rate-limiting enzyme in PGF2α synthesis, Cox-2, was induced in both CL with or without luteolytic capacity. Taken together these results indicate that luteolytic capacity is associated with differential effects of PGF2α on numerous biosynthetic and signaling pathways. A better understanding of how these pathways are regulated may allow improved therapies for contraception in humans and animals by causing a decline in progesterone production and improved pregnancy outcome by enhancing progesterone production.