Ensio Norjavaara

Synthesis of prostaglandin F2α, E2 and prostacyclin in isolated corpora lutea of adult pseudopregnant rats throughout the luteal life-span

The ability of de novo biosynthesis of prostaglandins (PGs) in individual whole corpora lutea (CL) obtained from sterile-mated adult pseudopregnant rats on different days of the luteal phase and the post-luteolytic period was evaluated. Production of PGs, progesterone and 20 alpha-dihydroprogesterone were determined after in vitro incubation of CL extirpated from Day 2 to Day 19 after mating. A time-relationship with increased accumulation of PGs in the medium was demonstrated from 18 s to 5 h, with large increments during the first 30 min. Basal accumulation of PGs in the incubation medium was highest for 6-keto-PGF1 alpha (the stable metabolite of prostacyclin) greater than PGE2 greater than PGF2 alpha greater than thromboxane B2 (TXB2) and basal accumulation of PGF2 alpha and PGE2 measured in the medium was maximal on Day 10-11 of pseudopregnancy, concomitantly with a decline in secretion of progesterone. Addition of arachidonic acid (AA) dose-dependently increased synthesis of PGs, with absolute amounts of PGE2 greater than 6-keto-PGF1 alpha greater than PGF2 alpha greater than TXB2 and addition of 14 microM indomethacin markedly inhibited accumulation of all PGs measured. Luteinizing hormone (LH, 10 micrograms/ml) stimulated progesterone secretion on all days during pseudopregnancy, but not on the post-luteolytic Day 19. LH increased PGF2 alpha, PGE2 and 6-keto-PGF1 alpha secretion on Day 13 of pseudopregnancy by 76%, 91% and 28%, respectively, but not on the other days tested. Furthermore, stimulation of PG-synthesis by addition of AA abrogated the LH-induced progesterone accumulation markedly, but only on Day 13 of pseudopregnancy. Epinephrine (5 micrograms/ml) increased production of progesterone and also PGs, but only on Day 2 of pseudopregnancy, whereas oxytocin (100 mIU/ml) was found to be without effect on progesterone as well as PG secretion on all days tested. The results of the present study demonstrates the independent ability of the rat CL to synthesize PGG/PGH2-derived prostaglandins, including the putative luteolysin PGF2 alpha. Secondly, we demonstrate that LH and AA-induced increases in PGF2 alpha and PGE2 production during the luteolytic period, may be an autocrine or paracrine mechanism involved in luteolysis.

Development of Sensitivity to Catecholamines in Granulosa and Luteal Cells

Catecholamines have a wide variety of physiological effects on a number of organ systems, including the nervous system, the circulation and the metabolism. The first indications that catecholamines could influence gonadal function was probably the observation that stress can depress the androgen blood level in the male (Levin et al., 1967) and the observation that the fibromuscular layer surrounding the mature follicle can increase the intrafollicular pressure and possibly promote the ovulatory process (Walles et al., 1976). The role of these effects are, however, still under debate. Catecholamines also have effects on the blood vessels of the gonads resulting in changes in blood flow (e.g. Damber et al., 1982; Selstam, 1975). The arteries are innervated (Burder, 1978), but the role of catecholamines on gonadal blood flow also remains to be investigated.

Vascular resistance is decreased in the luteal rat ovary by a 20 minute continuous infusion of noradrenaline.

The effect of a 20 min continuous infusion of noradrenaline (2 nanomoles/min) on the blood flow and vascular resistance of 2-, 6- and 11-day-old corpora lutea from adult pseudopregnant rats was studied. Pseudopregnancy was induced by mating with vasectomized male rats. The blood flow of the corpus luteum and the remaining ovary was measured with the microsphere technique. The basal blood flow varied between the luteal ages studied and was highest at day 6 of pseudopregnancy. Noradrenaline induced a two-fold increase in the blood flow of the corpus luteum at the luteal ages studied. The vascular resistance (blood pressure/blood flow) decreased for all luteal ages, while the vascular resistance for kidney, spleen and diaphragm was unchanged. Antidiuretic hormone was found to markedly decrease the luteal blood flow and the vascular resistance remained increased. The effect of noradrenaline infusion on the luteal blood flow thus in contrast to other vasoactive substances is biphasic, with an initial vasoconstriction followed by vasodilatation.

Physiological Role of Endogenously Derived PGF2α in Regulation of Corpus Luteum Function in the Rat

Prostaglandins are considered to be local hormones with rapid metabolism acting near their site of synthesis (1). There are two processes in ovarian function where prostaglandins are implicated to have an important regulatory role, namely, ovulation and luteolysis. All the active endocrine cells of the different compartments in the ovary (e.g., granulosa cells, theca cells, interstitial cells, and luteal cells) are capable of prostaglandin production (2). In most mammalian species, prostaglandin F2α (PGF2α) is recognized to have a decisive role in the functional regression of the corpus luteum. This mini review will concentrate on the physiological importance of endogenously derived PGF2α in regulation of luteal function in the rat.