Stimulation of progesterone secretion by recombinant follistatin-288 in human granulosa cells.
The effects of recombinant human follistatin (follistatin-288) on basal and hCG-stimulated progesterone secretion were examined in cultured human granulosa cells. Follistatin increased progesterone secretion in a dose-dependent manner. However, follistatin did not augment hCG- or cAMP-stimulated progesterone secretion. Time-course analysis revealed that follistatin increased progesterone secretion after 24 h of incubation. Follistatin also enhanced basal, but not hCG-stimulated, 20 alpha-hydroxyprogesterone accumulation, indicating that the increase in progesterone accumulation was not due to a blockade of the 20 alpha-hydroxylase metabolic pathway. In the presence of the phosphodiesterase inhibitor isobutylmethylxanthine, follistatin significantly increased intracellular cAMP accumulation to levels comparable to those induced by 1 IU/ml hCG. These results provide the first evidence of a stimulatory action of follistatin on progestin secretion in the human ovary, which is accompanied by an increased accumulation of intracellular cAMP levels. Follistatin may well be another potential regulator of steroid hormone production in human granulosa cells during the periovulatory period.
Department of Obstetrics and Gynecology, University of British Columbia, Grace Hospital, Vancouver, Canada.
W
W
Li
S
S
Khorasheh
B H
BH
Yuen
N
N
Ling
P C
PC
Leung
D004092:20-alpha-Dihydroprogesterone / Q000378:metabolism; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D038681:Follistatin; D006023:Glycoproteins / Q000494:pharmacology*; D006107:Granulosa Cells / Q000378:metabolism*; D006801:Humans; D011374:Progesterone / Q000378:metabolism*; D011372:Progestins / Q000378:metabolism; D011994:Recombinant Proteins; D013997:Time Factors
D006063:Chorionic Gonadotropin; D038681:Follistatin; D006023:Glycoproteins; D011372:Progestins; D011994:Recombinant Proteins; D004092:20-alpha-Dihydroprogesterone; D011374:Progesterone; D000242:Cyclic AMP