Induction of ovarian follicle luteinization by recombinant follicle-stimulating hormone.
Ovulation and subsequent luteal tissue formation are preceded by midcycle surges of both LH and FSH. Although LH has been widely known as the luteinizing hormone, a potential role for FSH in the luteinization process is possible. Our earlier studies using recombinant FSH (rcFSH) without LH contamination have shown that treatment with a surge dose of rcFSH induces ovulation of mature follicles in hypophysectomized rats. The present studies examined further whether FSH alone is sufficient to induce normal corpus luteum formation. Immature hypophysectomized rats were implanted with an estrogen pellet (10 mg diethylstilbestrol). Two days later, a minipump releasing 4 IU rcFSH/day was placed to induce follicular growth. Forty-eight hours after FSH treatment, both DES pellet and FSH minipump were removed, and rats were injected with a single sc dose of 40 IU rcFSH, 5 micrograms hCG, or saline. For some animals, oviducts were excised the following day to determine the number of ovulated oocytes. The remaining animals received, 2 days later, sc injections of 125 micrograms ovine PRL twice daily for 3 days to maintain luteal function. All rats that received a surge dose of rcFSH or hCG ovulated similar numbers of oocytes, whereas none of the control animals did. Ovaries and blood samples were obtained 5 days after the gonadotropin surge. rcFSH and hCG significantly increased ovarian weight to 73.9 +/- 4.8 and 94.7 +/- 5.6 mg, respectively, compared to 10.0 +/- 0.5 mg in controls. Serum progesterone levels were increased by 192- and 102-fold in rcFSH- and hCG-treated animals, respectively, compared with those in the saline-treated rats. rcFSH and hCG also induced a marked elevation of ovarian [125I]hCG binding (4.2 +/- 0.2 and 3.7 +/- 0.1 ng/mg ovary, respectively), whereas ovaries from control animals exhibited low binding (0.6 +/- 0.1 ng/mg ovary). These gonadotropin-induced increases in [125I]hCG binding were associated with similar elevations in the levels of three LH receptor transcripts of 2.5, 4.2, and 7.0 kilobases. Also, levels of the ovarian cholesterol side-chain cleavage enzyme (CYP 11A) mRNA (2 kilobases) were low in control animals, but increased 20.5- and 14.3-fold after surge doses of rcFSH and hCG, respectively. Accompanied by biochemical signs of luteinization, morphological features typical of luteinized ovaries were found in both rcFSH and hCG groups, showing the formation of large polyhedral lutein cells and small spindle-shaped lutein cells.(ABSTRACT TRUNCATED AT 400 WORDS)
Tapanainen
J S
JS
Department of Gynecology and Obstetrics, Stanford University Medical Center, California 94305.
Lapolt
P S
PS
Perlas
E
E
Hsueh
A J
AJ
D000818:Animals; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism; D006063:Chorionic Gonadotropin / Q000378:metabolism / Q000494:pharmacology; D003338:Corpus Luteum / Q000254:growth & development* / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D007016:Hypophysectomy; D009929:Organ Size / Q000187:drug effects; D006080:Ovarian Follicle / Q000187:drug effects* / Q000502:physiology; D010053:Ovary / Q000187:drug effects; D011374:Progesterone / Q000097:blood; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011974:Receptors, LH / Q000235:genetics; D011994:Recombinant Proteins
D006063:Chorionic Gonadotropin; D012333:RNA, Messenger; D011974:Receptors, LH; D011994:Recombinant Proteins; D011374:Progesterone; D005640:Follicle Stimulating Hormone; D002786:Cholesterol Side-Chain Cleavage Enzyme