Gonadotropin-induced up- and down-regulation of ovarian follicle-stimulating hormone (FSH) receptor gene expression in immature rats: effects of pregnant mare's serum gonadotropin, human chorionic gonadotropin, and recombinant FSH.
The actions of gonadotropins on ovarian differentiation are associated with dynamic changes in gonadotropin receptor content, presumably due to modulation of receptor gene expression. The present studies used a reverse transcription-polymerase chain reaction to obtain a rat FSH receptor cDNA fragment, followed by synthesis of a labeled cRNA probe to examine the regulation of FSH receptor mRNA levels during follicular maturation, ovulation, and luteinization. Northern blot analysis of ovarian RNA with the FSH receptor probe revealed two predominant hybridization signals of 7.0 and 2.5 kilobases (kb) as well as minor signals of 4.2 and 1.8 kb. Treatment of immature rats with PMSG (10 IU) to induce follicular development resulted in increased FSH receptor mRNA levels 24 h after treatment, with a further increase at 52 h, coincident with increased [125I]FSH binding. Subsequent treatment with an ovulatory dose of hCG decreased FSH binding and receptor mRNA levels by 6 h, with a maximal inhibition at 24 h after hCG. In luteinized ovaries obtained 3 and 5 days after hCG treatment, the 7.0-kb FSH receptor mRNA increased again, but no concomitant elevation of [125I]FSH binding was detected. We recently demonstrated that FSH treatment alone is capable of inducing follicular growth and ovulation, thus providing a unique model to evaluate the effects of FSH on regulation of its receptor gene. Immature hypophysectomized estrogen-treated rats were implanted with an osmotic minipump delivering recombinant human FSH (rcFSH; 4 IU/day) to stimulate follicle growth, followed 52 h later with a single injection (20 IU) of rcFSH to induce ovulation. Stimulation of follicular growth with rcFSH increased both FSH receptor binding and mRNA levels. In contrast, the ovulatory dose of rcFSH decreased FSH binding and receptor message levels within 12 h. Thus, gonadotropin regulation of ovarian FSH receptor content during follicular growth, ovulation, and luteinization is associated with similar changes in FSH receptor message levels. Also, studies using rcFSH demonstrate that both up- and down-regulation of FSH receptor gene expression can be induced by the homologous hormone at different stages of follicle development.
LaPolt
P S
PS
Department of Gynecology and Obstetrics, Stanford University School of Medicine, California 94305-5317.
Tilly
J L
JL
Aihara
T
T
Nishimori
K
K
Hsueh
A J
AJ
D000818:Animals; D015152:Blotting, Northern; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D004247:DNA / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects* / Q000235:genetics; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006062:Gonadotropins / Q000494:pharmacology*; D006064:Gonadotropins, Equine / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D009693:Nucleic Acid Hybridization; D010053:Ovary / Q000737:chemistry / Q000187:drug effects / Q000648:ultrastructure; D010060:Ovulation / Q000187:drug effects / Q000235:genetics; D016133:Polymerase Chain Reaction; D015347:RNA Probes; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D011962:Receptors, FSH / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects* / Q000235:genetics
D006063:Chorionic Gonadotropin; D006062:Gonadotropins; D006064:Gonadotropins, Equine; D007457:Iodine Radioisotopes; D015347:RNA Probes; D012333:RNA, Messenger; D011962:Receptors, FSH; D011994:Recombinant Proteins; D005640:Follicle Stimulating Hormone; D004247:DNA