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Stepwise activation of the gonadotropic signal transduction pathway, and the ability of prostaglandin F2alpha to inhibit this activated pathway.
- Source :
-
Endocrine [Endocrine] 1998 Jun; Vol. 8 (3), pp. 301-7. - Publication Year :
- 1998
-
Abstract
- Through selective activation of the gonadotropic signal transduction pathway, we have determined the probable site of the antigonadotropic effects of prostaglandin F2alpha (PGF2alpha) in the human granulosa-luteal cell (hGLC). The gonadotropic signal transduction pathway was activated at the level of the receptor (luteinizing hormone and beta-adrenergic), stimulatory G protein (Gs), adenylate cyclase (AC), and protein kinase A (PKA) by human chorionic gonadotropin (hCG) and isoproterenol (Iso), cholera toxin (CTX), forskolin, and dibutryl cAMP (Db cAMP), respectively. Concomitantly, the ability of PGF2alpha to inhibit progesterone production in response to the activation of this cascade at these different levels was examined. hGLCs were obtained from in vitro fertilization patients and were precultured for 8 d in Medium 199 supplemented with fetal bovine serum (M199; 10% FBS). Following the preculture period, cells were treated with either vehicle or one of the above activators of the gonadotropic pathway, either in the absence or presence of PGF2alpha (in M199; No FBS). Following the treatment period, media were collected and assayed for progesterone by RIA. Prostaglandin F2alpha (10(-6) M) significantly inhibited hCG (1 IU/mL), Iso (10(-5) M), CTX (1 microg/mL), and forskolin- (10(-5) M) stimulated progesterone production. Conversely, PGF2alpha did not inhibit progesterone production stimulated by a saturating concentration of Db cAMP (10(-6) M). The ability of PGF2alpha to inhibit hCG- or CTX-stimulated progesterone production was attenuated by pertussis toxin (PTX; 50 ng/mL). In conclusion, through a pertussis toxin-sensitive G protein, PGF2alpha inhibits progesterone production at a level below AC, and above the activation of PKA by cAMP.
- Subjects :
- Adenylyl Cyclases metabolism
Adrenergic beta-Agonists pharmacology
Animals
Bucladesine pharmacology
Cattle
Cells, Cultured
Cholera Toxin metabolism
Chorionic Gonadotropin pharmacology
Colforsin pharmacology
Corpus Luteum drug effects
Corpus Luteum metabolism
Cyclic AMP physiology
Cyclic AMP-Dependent Protein Kinases metabolism
DNA metabolism
Female
GTP-Binding Proteins physiology
Granulosa Cells drug effects
Granulosa Cells metabolism
Humans
Isoproterenol pharmacology
Chorionic Gonadotropin physiology
Dinoprost pharmacology
Signal Transduction drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1355-008X
- Volume :
- 8
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Endocrine
- Publication Type :
- Academic Journal
- Accession number :
- 9741835
- Full Text :
- https://doi.org/10.1385/endo:8:3:301