Studies concerning the hormonal induction of lactogenesis by prostaglandin F2α in pregnant rats

Bussmann, Leonardo E.; Deis, R. P.

doi:10.1016/0022-4731(79)90125-0

Cited by 84 publications

(53 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The stimulatory effect of PGF 2 ␣ on the activity of the 20␣-HSD enzyme in the rat corpus luteum is well recognized (5)(6)(7)(8). The corpus luteum expresses PGF 2 ␣ receptor (32)(33)(34) and is able to produce the ligand (35,36).…”

Section: Discussionmentioning

confidence: 99%

Prostaglandin F2α-induced Expression of 20α-Hydroxysteroid Dehydrogenase Involves the Transcription Factor NUR77

Stocco¹,

Zhong²,

Sugimoto³

et al. 2000

Journal of Biological Chemistry

120

View full text Add to dashboard Cite

Prostaglandin F 2 ␣ (PGF 2 ␣) binding to its receptor on the rat corpus luteum triggers various signal transduction pathways that lead to the activation of a steroidogenic enzyme, 20␣-hydroxysteroid dehydrogenase (20␣-HSD), which in turn catabolizes progesterone. The molecular mechanism underlying PGF 2 ␣-induced 20␣-HSD enzyme activity has not yet been explored. In this report we show, using mice lacking PGF 2 ␣ receptor and pregnant rats, that PGF 2 ␣ is responsible for the rapid and massive expression of the 20␣-HSD gene at the end of pregnancy leading to a decrease in progesterone secretion. We also present evidence that PGF 2 ␣ enhances 20␣-HSD promoter activity. We have determined a region upstream of the ؊1590 position in the 20␣-HSD promoter that confers regulation by PGF 2 ␣ in ovarian primary cells. This region encompasses a unique transcription factor-binding site with a sequence of a NUR77 response element. Deletion of this motif or overexpression of a NUR77 dominant negative protein caused a complete loss of 20␣-HSD promoter activation by PGF 2 ␣. NUR77 also transactivated the 20␣-HSD promoter in transient transfection experiments in corpus luteumderived cells (GG-CL). This induction required the NUR77-transactivating domain. We also show that PGF 2 ␣ induces a very rapid expression of NUR77 that binds to a distal response element located at ؊1599/ ؊1606 but does not interact with another proximal putative NUR77 response element located downstream in the promoter. A rapid increase in NUR77 mRNA was observed in mice corpora lutea just before parturition at a time when 20␣-HSD becomes expressed. This increase in the expression of both genes was not seen in PGF 2 ␣ receptor knockout mice. By using cyclosporin A and PGF 2 ␣ treatment, we established that inhibition of NUR77 DNA binding in vivo prevents PGF 2 ␣ induction of the 20␣-HSD gene in the corpus luteum. Taken together, our results demonstrate, for the first time, that PGF 2 ␣ induces in the corpus luteum the expression of the nuclear orphan receptor and transcription factor, NUR77, which in turn leads to the transcriptional stimulation of 20␣-HSD, triggering the decrease in serum progesterone essential for parturition.In all mammalian species, progesterone plays an essential role in reproduction. The precise timing of both the synthesis and degradation of this steroid hormone is crucial for reproductive success. The expression of enzymes implicated in the synthesis and catabolism of progesterone, therefore, needs to be accurately regulated during the different reproductive states of the animal. In rodents, the corpus luteum, which is the only source of progesterone throughout pregnancy (1), is also able to express the enzyme 20␣-hydroxysteroid dehydrogenase (20␣-HSD)1 that converts progesterone into a biologically inactive steroid, thus playing a key role in the termination of pregnancy and allowing parturition to occur (2). Due to the detrimental effect of 20␣-HSD on luteal progesterone secretion, the corpus luteum of pregnancy does not express...

show abstract

Section: Discussionmentioning

confidence: 99%

Prostaglandin F2α-induced Expression of 20α-Hydroxysteroid Dehydrogenase Involves the Transcription Factor NUR77

Stocco¹,

Zhong²,

Sugimoto³

et al. 2000

Journal of Biological Chemistry

120

View full text Add to dashboard Cite

show abstract

“…Serum progesterone concentrations were assessed by radioimmunoassay and placental lactogen by a radioreceptor assay as described previously (Bussmann & Deis, 1979). All serum samples were measured in a single assay to eliminate interassay variations.…”

Section: Methodsmentioning

confidence: 99%

“…The rapid induction of 20a-HSD activity after PGF-2a treatment suggests an effect of the PGF2a on the synthesis of this enzyme (Bussmann & Deis, 1979). This is also indicated by the abolition to a different extent by indomethacin of the inductions of enzyme activity caused either in early pregnancy with 2-bromo-a-ergocriptine or in late pregnancy with aminoglutethimide or hCG (Hickman-Smith & Kuhn, 1976).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Prostaglandin F-2 receptors in corpora lutea of pregnant rats and relationship with induction of 20 -hydroxysteroid dehydrogenase

Bussmann¹

1989

Reproduction

View full text Add to dashboard Cite

show abstract

“…In one experimental series we tested the effect of a Zn deficiency in rats upon their response to PGF2a by using a protocol successfully employed in an earlier study by Bussman & Deis (1979). Rats in each of the three diet groups were given 150,ug each of the tromethamine salt of PGF2a0 (112,ug of PGF2a; Upjohn, Crawley, West Sussex, U.K.) by intraperitoneal injection at 1 1.00h on the morning of day 20 of gestation and again at 15.00h on the afternoon of the same day.…”

Section: Materials and Methods Animal Management And Experimental Designmentioning

confidence: 99%

Studies on the role of zinc in parturition in the rat

Bunce¹,

Wilson²,

Mills³

et al. 1983

Biochemical Journal

View full text Add to dashboard Cite

1. Pregnant rats were fed either low (<1 p.p.m.) Zn or control (40p.p.m. Zn) diets from day 10 of gestation. They were killed at intervals during the last 96h preceding the normal time for onset of parturition, and differences in plasma progesterone, oestradiol-17, and ovarian 20a-hydroxysteroid dehydrogenase were assessed. 2. Gestation was prolonged in Zn-deficient rats. 3. Although the preparturient decline in plasma progesterone began at the same time in all groups, at term, plasma progesterone concentration in Zn-deficient rats remained significantly higher than in normal females. 4. Induction of ovarian 20a-hydroxysteroid dehydrogenase activity was delayed by about 8h by Zn deficiency. This delay was not observed if prostaglandin F2. was injected previously. 5. The results suggest a Zn-dependent step(s) in uterine synthesis and/or release of prostanoids.Zinc was first reported to be required for normal parturition in the rat by Apgar (1968a). Female rats fed a diet containing 1 p.p.m. or less of Zn beginning on the first day after mating displayed loss of appetite and lethargy. Harderian-gland pigment often accumulated on the face and paws. Delivery was difficult and prolonged and accompanied by excessive bleeding, and most of the neonates were abandoned and placentae were left unconsumed. Further studies (Apgar, 1968b(Apgar, , 1970(Apgar, , 1972(Apgar, , 1973(Apgar, , 1975(Apgar, , 1976(Apgar, , 1977aGombe et al., 1973) showed that such effects were relatively specific to Zn deficiency and were not induced by restriction either of total food intake (pair-feeding) or

show abstract

Studies concerning the hormonal induction of lactogenesis by prostaglandin F2α in pregnant rats

Cited by 84 publications

References 24 publications

Prostaglandin F2α-induced Expression of 20α-Hydroxysteroid Dehydrogenase Involves the Transcription Factor NUR77

Prostaglandin F2α-induced Expression of 20α-Hydroxysteroid Dehydrogenase Involves the Transcription Factor NUR77

Prostaglandin F-2 receptors in corpora lutea of pregnant rats and relationship with induction of 20 -hydroxysteroid dehydrogenase

Studies on the role of zinc in parturition in the rat

Contact Info

Product

Resources

About