Follicle-stimulating hormone receptor expression in the rat ovary: increases during prepubertal development and regulation by the opposing actions of transforming growth factors beta and alpha.
Pituitary gonadotropin FSH acts exclusively on ovarian granulosa cells by binding to specific plasma membrane receptors. Transforming growth factors alpha and beta (TGF alpha and TGF beta), produced locally within the ovary, have been shown to regulate diverse follicle functions, although their potential role in the regulation of FSH receptors has not been assessed. Our first objective was to demonstrate developmental changes in the expression of FSH receptor gene and protein; we then analyzed the regulation of FSH receptor expression by TGF beta s and TGF alpha in cultured granulosa cells. Analysis of steady-state FSH receptor mRNA and protein levels in neonatal and prepubertal ovaries revealed the existence of two predominant FSH receptor mRNA transcripts, 7.0 and 2.5 kb in size, showing a dramatic increase between Day 15 and Day 18 of age followed by a plateau up to 27 days of age. A close parallelism in the developmental changes in FSH receptor mRNA levels and FSH receptor content was observed. Cultured granulosa cells obtained from estrogen-treated immature rats exhibited FSH receptor transcripts similar in size to those seen in whole ovaries. Treatment of granulosa cells for 48 h with TGF beta 1 increased the levels of FSH receptor mRNA for both the 7.0- and 2.5-kb transcripts in a dose-dependent manner (ED50, 1.5 ng/ml), with a maximal 4.0 +/- 0.8-fold increase over control levels observed in response to 10 ng/ml TGF beta 1. Also, TGF beta 2 was as potent as TGF beta 1 in increasing FSH receptor mRNA levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Dunkel
L
L
Department of Gynecology and Obstetrics, Stanford University School of Medicine, California 94305-5317.
Tilly
J L
JL
Shikone
T
T
Nishimori
K
K
Hsueh
A J
AJ
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D005786:Gene Expression Regulation; D006107:Granulosa Cells / Q000378:metabolism; D007700:Kinetics; D010053:Ovary / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011962:Receptors, FSH / Q000235:genetics* / Q000378:metabolism; D012741:Sexual Maturation / Q000502:physiology*; D016211:Transforming Growth Factor alpha / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000494:pharmacology*
D012333:RNA, Messenger; D011962:Receptors, FSH; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; D005640:Follicle Stimulating Hormone