FUNCTIONAL LUTEOLYSIS IN THE PSEUDOPREGNANT RAT: EFFECTS OF PROSTAGLANDIN F2α AND 16-Aryloxy PROSTAGLANDIN F2α IN VITRO

Abstract

The present work concerns the luteolytic effects of prostaglandin (PG) F2 alpha and its analogue, 16-aryloxy PGF2 alpha, upon isolated luteal cells. Varying doses of these two prostaglandins were incubated with cells in the presence or absence of an optimum stimulatory dose of LH (1 microgram/ml). The total contents of progesterone and 20 alpha-dihydroprogesterone in flasks were determined after the incubation periods by radioimmunoassay. Both prostaglandins inhibited basal synthesis of progesterone and 20 alpha-dihydroprogesterone, maximum inhibition occurring at concentrations of either PG of between 250 and 500 ng/ml. In this dose range both prostaglandins were found to abolish LH-stimulated progestogen synthesis completely. These effects were discernible within 5 min of incubation. The studies demonstrated that the onset of PG-induced luteolysis in vitro is characterized by an inhibition of the biosynthesis of both progesterone and its weakly progestogenic metabolite, 20 alpha-dihydroprogesterone; induction of 20 alpha-hydroxysteroid dehydrogenase activity by either PG was not found in incubations extending up to 60 min. In contrast to their relative potencies in vivo, PGF2 alpha and 16-aryloxy PGF2 alpha were essentially equipotent in this in-vitro system.

Prostaglandin F2α-induced functional luteolysis: interactions of LH, prostaglandin F2α and forskolin in cyclic AMP and progesterone synthesis in isolated rat luteal cells

“…This in-vitro antigonadotrophic action of PGF2a and its analogues is well docu¬ mented (e.g. Hall & Robinson, 1979), and specific receptors for LH (see review by Niswender, Sawyer, Chen & Endres, 1980) and PGF2a (Wright, Pang & Behrman, 1980) have been demonstrated on rat luteal cells. Although, chronically, PGF2a causes downregulation of LH receptors within 12-24 h (Hichens, Grinwich & Behrman, 1974;Behrman, Grinwich & Hichens, 1976), and affects uptake of gonadotrophin , it does not affect the avidity of binding of LH to its receptor (Thomas et al 1978).…”

“…Gonadotrophins were given in 0-2 ml 0-9% (w/v) NaCl. This schedule achieves superluteinization and various aspects of this animal model have been characterized previously in our laboratory (Tan & Robinson, 1977;Hall & Robinson, 1979).…”

“…Isolated cells were prepared by a modification of the methods of Clark, Azhar & Menon (1976) and Hall & Robinson (1979). Six days after hCG injection groups of 8-16 animals were killed by cervical dislocation.…”

PROGESTERONE PRODUCTION BY DISPERSED CELLS FROM HUMAN CORPUS LUTEUM: STIMULATION BY GONADOTROPHINS AND PROSTAGLANDIN F2α; LACK OF RESPONSE TO ADRENALINE AND ISOPRENALINE

“…This conclusion is not substantiated by recent reports describing inhibitory effects of PGF2o! on gonadotrophin-stimulated progesterone production by dispersed cells of rat corpus luteum (Thomas, Dorflinger & Behrman, 1978;Hall & Robinson, 1979) suggesting that tissue integrity is not a requirement for the inhibitory actions of PGF2o[ in the nonprimate corpus luteum. The short-term effects of PGF2oL on cell suspensions from human corpus luteum are, therefore, quite distinct from those observed using dispersed luteal cells prepared from the non-primate ovary.…”

Ovarian production of progesterone and 20α-dihydroprogesterone in vitro following prostaglandin F2α induced luteolysis in the superluteinized rat

“…Thus PGF2a induced luteolysis in vivo and stimulated progesterone secretion in vitro (Speroff & Ramwell 1970), inhibited progesterone secretion in vitro (Hall & Robinson 1979) and inhibited LH-stimulated progesterone secretion in vitro (Thomas et al 1978) On the other hand, PGF2a treatment both in vivo and in vitro inhibited LH stimulated adenylyl cyclase activity (Khan et al 1979;Wakeling & Green 1981). Thus PGF2a induced luteolysis in vivo and stimulated progesterone secretion in vitro (Speroff & Ramwell 1970), inhibited progesterone secretion in vitro (Hall & Robinson 1979) and inhibited LH-stimulated progesterone secretion in vitro (Thomas et al 1978) On the other hand, PGF2a treatment both in vivo and in vitro inhibited LH stimulated adenylyl cyclase activity (Khan et al 1979;Wakeling & Green 1981).…”