OVARY - C
Wednesday, August 4, 2004
10:30 AM–12:30 PM
(764) PROSTAGLANDIN BIOSYNTHESIS, TRANSPORT AND SIGNALING IN CORPUS LUTEUM: A BASIS FOR AUTOREGULATION OF LUTEAL FUNCTION.
Arosh, Joe1, Banu, Sakhila1, Chapdelaine, Pierre1, Madore, Eric1, Sirois, Jean2, Fortier, Michel1, 3, 1 Unité d'Ontogénie and Reproduction, CHUL, CRBR, Université Laval, Québec, PQ, Canada2 CRRA, Départment de biomédecine vétérinaire, Université de Montréal, Ste-Hyacinthe, PQ, Canada3 Départment d' Obstétrique et Gynécologie, Université Laval, Québec, PQ, Canada
ABSTRACT- The corpus luteum (CL) is a transient ovarian endocrine gland formed from the ovulated follicle. The primary secretory product of the CL is progesterone (P4) which is essential for establishment and maintenance of pregnancy as well as ovarian cyclicity in most mammals. Defect in luteal function has been associated with infertility and abortion. In the cyclic female, the life span of CL is characterized by luteal development, maintenance and regression regulated by complex interactions between luteotrophic and luteolytic mediators. It is universally accepted that PGF2 is the luteolysin while PGE2 is considered as a luteotropin in most mammals irrespective of origin either uterus or CL. New emerging concepts propose autocrine and paracrine actions of luteal PGs in the regulation of CL function. However, there is no report on selective biosynthesis and cellular transport of luteal PGE2 and PGF2 in the CL of any species. We have studied the expression of enzymes involved in the metabolism of PGE2 and PGF2, cyclooxygenase (COX) 1 and 2, PG synthases (PGES and PGFS), prostaglandin 15-dehydrogenase (PGDH), and PG transporter (PGT) as well as receptors (EP2, EP3 and FP) throughout the CL life span using a bovine model. CLs were collected and classified into 7 groups covering the entire estrous cycle. Expression analyses were performed using LightCycler, Northern and Western blots. COX-1, PGFS and PGDH are expressed at constant levels whereas COX-2, PGES, PGT, EP2, EP3 and FP are highly modulated and more highly expressed at specific phases of the CL life span. The PG components are preferentially expressed in large luteal cells. The results indicate that PGE2 biosynthesis, transport and signaling cascades are selectively activated during luteal maintenance. By contrast PGF2 system is activated during luteal regression. The information obtained from this study may be particularly relevant to the human where extraluteal PGs do not appear to contribute to luteolysis, and open a new research avenue in the field of CL biology. Collectively, our results suggest an integrated role for luteal PGE2 and PGF2 in autoregulation of CL function and thus strongly support the emerging concept that in addition to extraluteal /endometrial sources, locally produced PGs contribute to the regulation of CL function and life span.
KEY WORDS: PG metabolic enzymes, PG transporter, CL, PG receptors