Endothelin-1 is an autocrine/paracrine regulator of porcine granulosa cells.
We studied whether a novel vasoconstrictor, endothelin-1 (ET-1), is synthesized by and released from porcine granulosa cells, and whether ET-1 acts directly on granulosa cells in an autocrine/paracrine fashion. The dilution curve of the conditioned medium from cultured porcine granulosa cells was parallel to a standard curve of ET-1 in RIA. Reverse-phase HPLC of the conditioned media from the granulosa cells revealed a major peak of ET-1-like immunoreactivity (ET-1-LI) coeluting with standard ET-1. ET-1-LI was released from cultured porcine granulosa cells as a function of time. Northern blot analysis demonstrated the expression of mRNA for prepro-ET-1 in the granulosa cells. We demonstrated the presence of ET-1 in the follicular fluid of porcine ovaries, and that the concentration of ET-1 in large follicles was higher than that in small-medium follicles. ET-1 dose-dependently stimulated cell growth and DNA synthesis in porcine granulosa cells. ET-1 inhibited the FSH- and hCG stimulated accumulation of progesterone in porcine granulosa cells in long-term incubation. These findings suggest that ET-1 produced by porcine granulosa cells may function as an autocrine/paracrine growth factor and modulator of steroidogenesis in ovarian granulosa cells.
Department of Obstetrics and Gynecology, Faculty of Medicine, Tokyo Medical and Dental University, Japan.
S
S
Kamada
T
T
Kubota
Y
Y
Hirata
T
T
Imai
K
K
Ohta
M
M
Taguchi
F
F
Marumo
T
T
Aso
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D016232:Endothelins / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D005260:Female; D006107:Granulosa Cells / Q000378:metabolism*; D011374:Progesterone / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D013552:Swine / Q000378:metabolism*
D016232:Endothelins; D012333:RNA, Messenger; D011374:Progesterone