Prostaglandin F_2α Receptor in Ovine corpora lutea

Abstract

Evidence is presented for the existence of a prostaglandin-F, receptor in ovine corpora lutea. Prostaglandin F,, was specifically bound to a particulate fraction of this tissue with a dissociation constant of 0.1 pM. Prostaglandins F1,, E, and E, had considerably less affinity for the receptor whereas prostaglandins A, and B, had little or no affinity. From a comparison of the binding constants of various prostaglandins and related compounds it could be concluded that the carboxyl group, the three hydroxyl groups and the 5,6-cis double bond (but not the 13,14-trans double bond) of prostaglandin F,, were all important for binding to the receptor.The uterus is required for normal cyclic regression of corpora lutea in a number of mammalian species [l, 21. Pharriss and Wyngarden first postulated that prostaglandin F, was responsible for this phenomenon [3] and subsequent experiments have shown that this prostaglandin is luteolytic in several animals [2]. Conclusive evidence was recently presented that prostaglandin F,, is a luteolytic hormone in the sheep [4]; it was released in relatively high concentrations from the uterus a t the time of luteal regression and was transferred from the utero-ovarian vein to the ovarian artery by a counter-current mechanism [4].The mechanism of the luteolytic effect of prostaglandin F,, is unknown. It has been proposed that prostaglandin F,, acts luteolytically by restricting the blood flow through the ovary[3], but subsequent experiments [5,6] have not substantiated this hypothesis. Prostaglandin F,, has been found to depress cholesterol ester synthetase activity in rat ovaries and it was suggested [7] that this might be the mechanism for the reduction in progesterone synthesis caused by prostaglandin F, in vivo [Z-41. I n bovine corpora latea slices prostaglandins E,, E,, F,, and A, (decreasing order of effectiveness) stimulated rather than inhibited Abbreviation. Me,Si, trimethylsilyl. Trivial Names. Prostaglandin F,,, 9a,llor,l5(S)-trihydroxyprost-l3-trans-enoic acid; prostaglandin FZa, 9a,l la, 15(S)-trihydroxyprosta-5-cis,13-truns-dienoic acid; prostaglandin F,b, 9~,11~-15(5)-trihydroxyprosta-5-cis,l3-trun~-dienoic acid ; prostaglandin El, 11 a, 15-(S)-dihydroxy-9-ketoprost-13-trans-enoic acid; prostaglandin E,, lla,15(S)-dihydroxy-9-ketoprosta-5-cis,13-truns-dienoic acid; prostaglandin A,, 15(S)-hydroxy-9-ketoprosta-10,13-trans-dienoic acid; prostaglandin A,, 15(S)-hydroxy-9-ketoprosta-5-cis,-10,13-trans-trienoio acid; prostaglandin B,, 15(S)-hydroxy-9-ketoprosta-5-cis,S( 12),13-trans-trienoic acid.

Prostaglandin E-2 as a potential luteotrophic agent during early pregnancy in cattle

“…There is some evidence that this may be the case, for the secretion of PGF-2a by luteal cells in response to LH stimulation has been reported (Shemesh & Hansel, 1975), and the luteal phospholipase activity is increased after stimulation by ß-adrenergic agents (Hirata & Axelrod, 1980). Alternatively, PGE-2, which has been demonstrated to bind to the PGF-2a receptor in the sheep corpus luteum (Powell et al, 1974), may therefore activate PGF-2a-dependent pathways within lutein cells. However, the observation that PGE-2 had only an inhibitory effect at low concentrations cannot easily be interpreted in terms of the above suggestions.…”

High‐affinity binding sites for 12(S)‐hydroxy‐5,8,10,14‐eicosatetraenoic acid (12(S)‐HETE) in carcinoma cells

“…A binding assay was developed and specific binding was demonstrated. bovine and ovine corpora lutea with f&s of 50 nM [19] and 100 nM [20], respectively. The binding site described here was highly specific for 12(S)-HETE.…”

Estrogen-directed synthesis of specific prostaglandins in uterus.

“…Such hyperemia has been related to elevations in prostaglandin E (PGE) levels (5,6). These findings, plus new data demonstrating the existence of receptors unique to PGE1 and PGF2, in the uterus (7) and corpus luteum (8,9), pose the possibility that PGEs and PGF2a,, produced in the uterus as a consequence of estrogen action, play distinctly different roles in the reproductive processes.…”